Embracing Failure: Nurturing Learning and Well-Being in Anesthesiology and Perioperative Medicine.

Failure, ubiquitous in life and medical practice, offers myriad opportunities for learning and growth alongside challenges to overall well-being. In this article, we explore the nature of failure, it's sources and impacts in perioperative medicine, and the specific challenges it brings to trainee well-being. With a deeper understanding of the societal, psychological and cognitive determinants and effects of failure, we propose solutions in order to harness the opportunities inherent in failures to create brave and supportive learning environments conducive to both education and well-being.

Sins of omission: A meta-research study evaluating the omission of operability in published retrospective comparisons of surgery with stereotactic body radiotherapy in patients with early-stage non-small cell lung cancer.

INTRODUCTION: Patients receiving stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) are typically inoperable, in concordance with guidelines that advocate surgical resection as preferred treatment for operable patients. This differential treatment allocation complicates retrospective comparisons of surgery with SBRT by introducing the potential for confounding by operability. METHODS: PubMed was queried for manuscripts reporting primary data from retrospective comparisons of overall survival (OS) between patients undergoing surgery versus SBRT for early-stage NSCLC. Each manuscript was categorized for two outcomes: (1) whether treatment allocation was based on a determination of patient operability, and (2) whether a direct OS comparison between operable SBRT patients and surgically treated patients was included. Associations with variables of interest were measured with statistical significance prespecified at p < 0.10. RESULTS: From 3,072 manuscripts identified in our query, sixty-one analyses met screening criteria. Twenty-one (34 %) reported operability status influencing treatment allocation. These were more likely to be published in journals with a surgical focus (52 vs 20 %) and impact factor < 5 (81 vs 58 %), and to contain cohorts from institutional datasets (81 vs 55 %), and to have a radiation oncologist as first (43 vs 25 %) or senior (43 vs 28 %) author. Seven (11 %) manuscripts featured a direct OS comparison between SBRT and surgery. CONCLUSION: Nearly-two-thirds of peer-reviewed retrospective studies that have compared OS between surgery and SBRT for early-stage NSCLC lack information on patient operability status, and nearly 90% lack a direct comparison between operable SBRT patients and those receiving surgery.

Guidelines for the management of diabetes services and patients during the COVID-19 pandemic.

The UK National Diabetes Inpatient COVID Response Group was formed at the end of March 2020 to support the provision of diabetes inpatient care during the COVID pandemic. It was formed in response to two emerging needs. First to ensure that basic diabetes services are secured and maintained at a time when there was a call for re-deployment to support the need for general medical expertise across secondary care services. The second was to provide simple safe diabetes guidelines for use by specialists and non-specialists treating inpatients with or suspected of COVID-19 infection. To date the group, comprising UK-based specialists in diabetes, pharmacy and psychology, have produced two sets of guidelines which will be continually revised as new evidence emerges. It is supported by Diabetes UK, the Association of British Clinical Diabetologists and NHS England.

Guidelines for the management of diabetes in care homes during the Covid-19 pandemic.

The National Diabetes Stakeholders Covid-19 Response Group was formed in early April 2020 as a rapid action by the Joint British Diabetes Societies for Inpatient Care, Diabetes UK, the Association of British Clinical Diabetologists, and Diabetes Frail to address and support the special needs of residents with diabetes in UK care homes during Covid-19. It was obvious that the care home sector was becoming a second wave of Covid-19 infection and that those with diabetes residing in care homes were at increased risk not only of susceptibility to infection but also to poorer outcomes. Its key purposes included minimising the morbidity and mortality associated with Covid-19 and assisting care staff to identify those residents with diabetes at highest risk of Covid-19 infection. The guidance was particularly created for care home managers, other care home staff, and specialist and non-specialist community nursing teams. The guidance covers the management of hyperglycaemia by discussion of various clinical scenarios that could arise, the management of hypoglycaemia, foot care and end of life care. In addition, it outlines the conditions where hospital admission is required. The guidance should be regarded as interim and will be updated as further medical and scientific evidence becomes available.

Late referral of cancer patients with malnutrition to dietitians: a prospective study of clinical practice.

PURPOSE: Malnutrition (MN) in cancer is common but underdiagnosed. Dietitian referrals may not occur until MN is established. We investigated cancer patient characteristics (demographics, nutritional status, and nutrition barriers) on referral to oncology dietitians. We also examined referral practices and prevalence of missed referral opportunities. METHODS: This was a naturalistic multi-site study of clinical practice. Data from consecutive referrals were collected in inpatient and outpatient settings. Demographics, nutritional status (weight, body mass index (BMI), weight loss in the preceding 3-6 months, oral intake, nutrition barriers), referral reasons, and use of screening were recorded. Missed opportunities for earlier referral were also noted. RESULTS: Two hundred patients were included (60% male, 51% inpatients). Half had gastrointestinal and hepatobiliary cancers. The majority were on antitumor treatment. Two-thirds had lost ≥ 5% body weight. Forty percent were overweight or obese. Seventy percent had ≥ 2 nutritional barriers. Most common nutrition barriers were anorexia, nausea, and early satiety. Greater weight loss and lower food intake were associated with ≥ 2 barriers. Weight loss was the most common referral reason. Screening was used in 35%. Referrals should have occurred sooner in nearly half (45%, n = 89). CONCLUSIONS: Cancer patients were referred late to a dietitian, with multiple nutritional barriers. Most referrals were for established weight loss (WL). WL may be masked by pre-existing obesity. Almost half had missed earlier referral opportunities; screening was infrequent. Over one-quarter should have been re-referred sooner. There is a clear need for clinician education. Future research should investigate the optimal timing of dietitian referral and the best nutrition screening tools for use in cancer.

Comparison of survival between radiation therapy and trans-oral laser microsurgery for early glottic cancer patients; a retrospective cohort study.

BACKGROUND: The literature reports various treatment methodologies, such as trans-oral laser microsurgery, radiation therapy, total/partial laryngectomies, and concurrent radiation chemotherapy for patients with early larynx cancer. However, at the forefront of early glottis treatment is trans-oral laser microsurgery and radiation therapy, likely due to better functional and survival outcomes. Here we conduct the largest Canadian head-to-head comparison of consecutive patients treated with either radiation therapy or trans-oral laser microsurgery. Additionally, we compare these two treatments and their 5-year survival rates post treatment to add to the existing literature. METHODS: Charts of patients who were diagnosed with early glottic cancer between 2006 and 2013 were reviewed. Seventy-five patients were identified, and split into 2 groups based on their primary treatment, trans-oral laser microsurgery and radiation therapy. Kaplan-Meier survival curves, life-tables, and the log-rank statistic were reported to determine if there was a difference between the two treatment groups and their disease-specific survival, disease-free survival, and total laryngectomy-free survival. Additionally, each different survival analysis was stratified by potential confounding variables, to help conclude which treatment is more efficacious in this population. RESULTS: The 5-year disease-specific survival rate is 93.3 % σ = 0.063 and 90.8 % σ = 0.056 for patients treated with trans-oral laser microsurgery and radiation therapy, respectively (χ (2) < 0.001, p = 0.983). The disease free survival rate is 60.0 % (σ =0.121) for patients treated with trans-oral laser microsurgery, and 67.2 % (σ = 0.074) for those who received RT (χ (2) = 0.19, p = 0.663). Additionally, the total laryngectomy-free survival rate is 84.1 % (σ = 0.1) and 79.1 % (σ = 0.072) for patients' early glottic cancer treated by trans-oral laser microsurgery and radiation therapy, respectively (χ (2) = 0.235, p = 0.628). Chi-square analysis of age-group versus treatment group (χ (2) = 6.455, p = 0.04) and T-stage versus treatment group (χ (2) = 11.3, p = 0.001) revealed a statistically significant relationship, suggesting survival analysis should be stratified by these variables. However, after stratification, there was no statistically significant difference between the trans-oral laser microsurgery and radiation therapy groups in any of the survival analyses. CONCLUSION: No difference was demonstrated in the 5-year disease-specific survival, disease-free survival, and total laryngectomy-free survival, between the RT and TLM treatment groups. Additionally, both groups showed similar 5-year survival after stratifying by confounding variables.

Heat and moisture exchanger use reduces in-hospital complications following total laryngectomy: a case-control study.

BACKGROUND: Total laryngectomy (TL) is an appropriate oncologic operation for many patients with laryngeal cancer delivering excellent oncologic outcomes, however it remains beset with significant functional consequences. Following TL, the upper and lower airways are permanently disconnected, which causes unfiltered, cold air with reduced humidity to enter the tracheobronchial tree, resulting in mucus overproduction and an increase in the viscosity of the mucus. In response to this, Heat and moisture exchangers were developed to compensate for the lost functions of the upper respiratory tract and their effect on the patients' respiratory performance in addition to their quality of life. METHODS: The case records of 48 patients undergoing total laryngectomy were reviewed and data concerning demographics, surgical details, post-operative care requirements and adverse events was retrieved. Post hoc analysis of the case patients was undertaken to identify any benefit of using a heat and moisture exchanger (HME) system with particular reference to post-operative respiratory outcomes. RESULTS: There was no significant difference between case and control subjects based on demographics, extent of surgery or need for flap repair. 16 patients had used a HME and 32 patients had used external humidification (EH). Of those experiencing mucous plugging, only 3/24 (12.5 %) had used a HME system, in contrast to 21/24 (87.5 %) who used EH (Chi square = 9.375, p = 0.002). The odds ratio of having an adverse event if not using HME was 8.27 (CI = 1.94 - 35.71). Use of HME also significantly reduced the number of days requiring physiotherapy (1.75 days vs. 3.20 days, p = 0.034). CONCLUSION: Use of an HME system can reduce in-hospital complications, in particular episodes of mucus plugging, and post-operative care requirements. Furthermore, there is a cost benefit to using HME systems that warrants more widespread introduction of these devices in head and neck surgery centers.

National survey of the management of Diabetic Ketoacidosis (DKA) in the UK in 2014.

AIM: To examine, in a national survey, the outcomes of adult patients presenting with DKA in 2014, mapped against accepted UK national guidance. METHODS: Data were collected in a standardized form covering clinical and biochemical outcomes, risk and discharge planning. The form was sent to all UK diabetes specialist teams (n = 220). Anonymized data were collected on five consecutive patients admitted with DKA between 1 May 2014 and 30 November 2014. RESULTS: A total of 283 forms were received (n = 281 patients) from 72 hospitals, of which 71.4% used the national guidelines. The results showed that 7.8% of cases occurred in existing inpatients, 6.1% of admissions were newly diagnosed diabetes and 33.7% of patients had had at least one episode of DKA in the preceding year. The median times to starting 0.9% sodium chloride and intravenous insulin were 41.5 and 60 min, respectively. The median time to resolution was 18.7 h and the median length of hospital stay was 2.6 days. Significant adverse biochemical outcomes occurred, with 27.6% of patients developing hypoglycaemia and 55% reported as having hypokalaemia. There were also significant issues with care processes. Initial nurse-led observations were carried out well, but subsequent patient monitoring remained suboptimal. Most patients were not seen by a member of the diabetes specialist team during the first 6 h, but 95% were seen before discharge. A significant minority of discharge letters to primary care did not contain necessary information. CONCLUSION: Despite widespread adoption of national guidance, several areas of management of DKA are suboptimal, being associated with avoidable biochemical and clinical risk.

Cumulative effects of transcranial direct current stimulation on EEG oscillations and attention/working memory during subacute neurorehabilitation of traumatic brain injury.

OBJECTIVE: To investigate in a randomized, double-blind design, cumulative effects of anodal tDCS on EEG oscillations and neuropsychological tests among patients with traumatic brain injury (TBI) undergoing subacute neurorehabilitation. METHODS: Twenty-six patients were randomly assigned to active (n=13) or sham (n=13) tDCS groups. EEGs were recorded at 6 different time points, assessing both immediate and cumulative effects of tDCS on EEG oscillations. Twenty minute sessions of 1mA anodal stimulation to the left dorsolateral prefrontal cortex (F3, cathode placed at right supraorbital site, Fp2), were provided on 10 consecutive days. Neuropsychological tests were administered before and after the series of tDCS sessions. RESULTS: Theta was significantly reduced for active tDCS patients following the first tDCS session. Delta decreased and alpha increased, both significantly, for the active tDCS group after 10 consecutive tDCS sessions. No significant changes were seen for sham group. Decreases in delta were significantly correlated with improved performance on neuropsychological tests for the active tDCS group to far greater degree than for the sham group. Participants in the active tDCS group who had excess slow EEG activity in their initial recordings showed greater improvement on neuropsychological tests than other groups. CONCLUSION: Results suggest that 10 anodal tDCS sessions may beneficially modulate regulation of cortical excitability for patients with TBI. SIGNIFICANCE: EEG-guided tDCS warrants further investigation as a potential intervention for TBI during subacute neurorehabilitation.

Nucleotides regulate secretion of the inflammatory chemokine CCL2 from human macrophages and monocytes.

CCL2 is an important inflammatory chemokine involved in monocyte recruitment to inflamed tissues. The extracellular nucleotide signalling molecules UTP and ATP acting via the P2Y2 receptor are known to induce CCL2 secretion in macrophages. We confirmed this in the human THP-1 monocytic cell line showing that UTP is as efficient as LPS at inducing CCL2 at early time points (2-6 hours). Expression and calcium mobilisation experiments confirmed the presence of functional P2Y2 receptors on THP-1 cells. UTP stimulation of human peripheral CD14+ monocytes showed low responses to LPS (4-hour stimulation) but a significant increase above background following 6 hours of treatment. The response to UTP in human monocytes was variable and required stimulation >6 hours. With such variability in response we looked for single nucleotide polymorphisms in P2RY2 that could affect the functional response. Sequencing of P2RY2 from THP-1 cells revealed the presence of a single nucleotide polymorphism altering amino acid 312 from arginine to serine (rs3741156). This polymorphism is relatively common at a frequency of 0.276 (n = 404 subjects). Finally, we investigated CCL2 secretion in response to LPS or UTP in human macrophages expressing 312Arg-P2Y2 or 312Ser-P2Y2 where only the latter exhibited significant UTP-induced CCL2 secretion (n = 5 donors per group).

Superabsorption of light via quantum engineering.

Almost 60 years ago Dicke introduced the term superradiance to describe a signature quantum effect: N atoms can collectively emit light at a rate proportional to N(2). Structures that superradiate must also have enhanced absorption, but the former always dominates in natural systems. Here we show that this restriction can be overcome by combining several well-established quantum control techniques. Our analytical and numerical calculations show that superabsorption can then be achieved and sustained in certain simple nanostructures, by trapping the system in a highly excited state through transition rate engineering. This opens the prospect of a new class of quantum nanotechnology with potential applications including photon detection and light-based power transmission. An array of quantum dots or a molecular ring structure could provide a suitable platform for an experimental demonstration.

Muckle-Wells syndrome without mutation in exon 3 of the NLRP3 gene, identified by evidence of excessive monocyte production of functional interleukin 1ß and rapid response to anakinra.

We report a man with lifelong urticaria, night sweats, arthralgia and lethargy. He had high levels of inflammatory markers and serum amyloid A, but no identifiable mutation in exon 3 of the NLRP3 (NOD-like receptor family, pyrin domain-1 containing 3) gene, and no relevant family history. We found marked production of functional interleukin (IL)-1 by the patient's monocytes at baseline and after stimulation with lipopolysaccharide. The patient made an immediate response to treatment with an IL-1ß receptor antagonist. We propose that this patient has Muckle-Wells syndrome without deafness, occurring de novo. Functional screening for IL-1 production could aid diagnosis in future similar cases.

Role of the trochlear nerve in eye abduction and frontal vision of the red-eared slider turtle (Trachemys scripta elegans).

Horizontal head rotation evokes significant responses from trochlear motoneurons of turtle that suggests they have a functional role in abduction of the eyes like that in frontal-eyed mammals. The finding is unexpected given that the turtle is generally considered lateral-eyed and assumed to have eye movements instead like that of lateral-eyed mammals, in which innervation of the superior oblique muscle by the trochlear nerve (nIV) produces intorsion, elevation, and adduction (not abduction). Using an isolated turtle head preparation with the brain removed, glass suction electrodes were used to stimulate nIV with trains of current pulses. Eyes were monitored via an infrared camera with the head placed in a gimble to quantify eye rotations and their directions. Stimulations of nIV evoked intorsion, elevation, and abduction. Dissection of the superior oblique muscle identified lines of action and a location of insertion on the eye, which supported kinematics evoked by nIV stimulation. Eye positions in alert behaving turtles with their head extended were compared with that when their heads were retracted in the carapace. When the head was retracted, there was a reduction in interpupillary distance and an increase in binocular overlap. Occlusion of peripheral fields by the carapace forces the turtle to a more frontal-eyed state, perhaps the reason for the action of abduction by the superior oblique muscle. These findings support why trochlear motoneurons in turtle respond in the same way as abducens motoneurons to horizontal rotations, an unusual characteristic of vestibulo-ocular physiology in comparison with other mammalian lateral-eyed species.

Culturing and direct PCR suggest prevalent host generalism among diverse fungal endophytes of tropical forest grasses.

Most studies examining endophytic fungi associated with grasses (Poaceae) have focused on agronomically important species in managed ecosystems or on wild grasses in subtropical, temperate and boreal grasslands. However grasses first arose in tropical forests, where they remain a significant and diverse component of understory and forest-edge communities. To provide a broader context for understanding grass-endophyte associations we characterized fungal endophyte communities inhabiting foliage of 11 species of phylogenetically diverse C(3) grasses in the understory of a lowland tropical forest at Barro Colorado Island, Panama. Our sample included members of early-arising subfamilies of Poaceae that are endemic to forests, as well as more recently arising subfamilies that transitioned to open environments. Isolation on culture media and direct PCR and cloning revealed that these grasses harbor species-rich and phylogenetically diverse communities that lack the endophytic Clavicipitaceae known from diverse woodland and pasture grasses in the temperate zone. Both the incidence and diversity of endophytes was consistent among grass species regardless of subfamily, clade affiliation or ancestral habitat use. Genotype and phylogenetic analyses suggest that these endophytic fungi are predominantly host generalists, shared not only among distinctive lineages of Poaceae but also with non-grass plants at the same site.

The value of periodic follow-up in the detection of recurrences after radical treatment in locally advanced head and neck cancer.

AIMS: To determine the value of routine follow-up in detecting and salvaging recurrence after radical treatment of locally advanced head and neck squamous cell carcinoma and to identify clinical or pathological prognostic factors that predicted for survival. MATERIALS AND METHODS: A retrospective medical chart review was conducted at the Odette Cancer Centre between January 2000 and May 2006. Two hundred and twenty-three patients with advanced (stage III or IV) squamous cell carcinoma of the head and neck who were treated with curative intent were reviewed. Recurrences were divided into local, regional or distant recurrences. The detection method for each recurrence was categorised as self or physician detected. A self-detected recurrence arose from symptoms that led to investigations that confirmed a recurrence (even if initiated at the time of a routine visit), whereas a physician-detected recurrence was found during the routine follow-up examination and was asymptomatic. RESULTS: There was no evidence to suggest a significant improvement in disease-free or overall survival in the physician-detected versus patient-detected groups. Regional and distant recurrences were only detected by physicians in one-fifth of cases and, overall, patients self-detected their own recurrence in two-thirds of the cases that experienced disease progression within the sample. Of the 12 clinical/pathological variables considered, only the response to treatment and perineural invasion were associated with survival. CONCLUSIONS: Current surveillance methods do not appear to improve cancer control in the stage III/IV head and neck squamous cell carcinoma population. However, technological advances and biomarker development may lead to surveillance technique enhancements. Also, post-treatment follow-up remains important for the evaluation of treatment results, emotional support and management of late complications. Among the clinical and pathological factors considered, only the treatment response and perineural invasion predicted survival.

A phylogenetic estimation of trophic transition networks for ascomycetous fungi: are lichens cradles of symbiotrophic fungal diversification?

Fungi associated with photosynthetic organisms are major determinants of terrestrial biomass, nutrient cycling, and ecosystem productivity from the poles to the equator. Whereas most fungi are known because of their fruit bodies (e.g., saprotrophs), symptoms (e.g., pathogens), or emergent properties as symbionts (e.g., lichens), the majority of fungal diversity is thought to occur among species that rarely manifest their presence with visual cues on their substrate (e.g., the apparently hyperdiverse fungal endophytes associated with foliage of plants). Fungal endophytes are ubiquitous among all lineages of land plants and live within overtly healthy tissues without causing disease, but the evolutionary origins of these highly diverse symbionts have not been explored. Here, we show that a key to understanding both the evolution of endophytism and the diversification of the most species-rich phylum of Fungi (Ascomycota) lies in endophyte-like fungi that can be isolated from the interior of apparently healthy lichens. These "endolichenic" fungi are distinct from lichen mycobionts or any other previously recognized fungal associates of lichens, represent the same major lineages of Ascomycota as do endophytes, largely parallel the high diversity of endophytes from the arctic to the tropics, and preferentially associate with green algal photobionts in lichen thalli. Using phylogenetic analyses that incorporate these newly recovered fungi and ancestral state reconstructions that take into account phylogenetic uncertainty, we show that endolichenism is an incubator for the evolution of endophytism. In turn, endophytism is evolutionarily transient, with endophytic lineages frequently transitioning to and from pathogenicity. Although symbiotrophic lineages frequently give rise to free-living saprotrophs, reversions to symbiosis are rare. Together, these results provide the basis for estimating trophic transition networks in the Ascomycota and provide a first set of hypotheses regarding the evolution of symbiotrophy and saprotrophy in the most species-rich fungal phylum. [Ancestral state reconstruction; Ascomycota; Bayesian analysis; endolichenic fungi; fungal endophytes; lichens; pathogens; phylogeny; saprotrophy; symbiotrophy; trophic transition network.].