Non-surgical external jugular vein catheterization using an ear vein access in piglets.

The objective of this study was to investigate the feasibility of external jugular vein catheterization through an ear vein in piglets. Forty-six sevoflurane-midazolam anaesthetized piglets were included. External jugular vein catheterization was conducted through the ear vein using the Seldinger technique. Part 1 (n = 27): optimal puncture site was based on the deltoid tuberosity as a landmark to reach the external jugular vein. The final position of the catheter was verified in 25 piglets using computer tomography. Catheterization time was recorded and patency of the catheter assessed by repeated blood sampling for up to 4 h. Part 2 (n = 19): ear vein catheterization was without taking into account any landmarks. Functionality for blood sampling was evaluated as described in part 1. Catheter advancement was possible in 25/27 and 18/19 piglets in parts 1 and 2, respectively. Median (range) time required for successful catheterization was 1.95 (1-10) min (n = 38). The deltoid tuberosity was a good landmark to reach the external jugular vein. But blood sampling was also possible through catheters ending slightly cranial to the external jugular vein. Despite successful catheter advancement, blood sampling was not possible from one catheter in each part of the study (total: two piglets). One of these catheters presented luminal damage, while the other one presented as normal after being removed from the animal. Summarizing, central vein catheterization through the ear vein was feasible in 93.5% and repeated blood sampling was possible in 89.1% of the piglets (n = 46).

Effects of moderate and severe arterial hypotension on intracerebral perfusion and brain tissue oxygenation in piglets.

BACKGROUND: Hypotension is common in anaesthetised children, and its impact on cerebral oxygenation is unknown. The goal of the present study was to investigate the effects of moderate systemic arterial hypotension (mHT) and severe hypotension (sHT) on cerebral perfusion and brain tissue oxygenation in piglets. METHODS: Twenty-seven anaesthetised piglets were randomly allocated to a control group, mHT group, or sHT group. Cerebral monitoring comprised a tissue oxygen partial pressure ( [Formula: see text] ) and laser Doppler (LD) perfusion probe advanced into the brain tissue, and a near-infrared spectroscopy sensor placed over the skin measuring regional oxygen saturation (rSO2). Arterial hypotension was induced by blood withdrawal and i.v. nitroprusside infusion [target MAP: 35-38 (mHT) and 27-30 (sHT) mm Hg]. Data were analysed at baseline, and every 20 min during and after treatment. RESULTS: Compared with control, [Formula: see text] decreased equally with mHT and sHT [mean (SD) after 60 min: control: 17.1 (6.4); mHT: 6.4 (3.6); sHT: 7.2 (4.3) mm Hg]. No differences between groups were detected for rSO2 and LD during treatment. However, in the sHT group, rSO2 increased after restoring normotension [from 49.3 (9.5) to 58.9 (8.9)% Post60]. sHT was associated with an increase in blood lactate [from 1.5 (0.4) to 2.4 (0.9) mmol L-1], and a decrease in bicarbonate [28 (2.4) to 25.8 (2.6) mmol L-1] and base excess [4.7 (1.9) to 2.0 (2.7) mmol L-1] between baseline and 60 min after the start of the experiment. CONCLUSIONS: Induction of mHT and sHT by hypovolaemia and nitroprusside infusion caused alterations in brain tissue oxygenation in a piglet model, but without detectable changes in brain tissue perfusion and regional oxygen saturation.

Systematic review of the neurocognitive outcomes used in studies of paediatric anaesthesia neurotoxicity.

BACKGROUND: Neurotoxicity of anaesthetics in developing brain cells is well documented in preclinical studies, yet results are conflicting in humans. The use of many and different outcome measures in human studies may contribute to this disagreement. METHODS: We conducted a systematic review to identify all measures used to assess long-term neurocognitive outcomes following general anaesthesia (GA) and surgery in children. The quality of studies was assessed according to the Newcastle-Ottawa Scale (NOS) for observational studies. PubMed/MEDLINE, EMBASE, Cinahl, Web of Science, and the Cochrane Library were searched for studies investigating neurocognitive outcome after GA in children <18 yr. RESULTS: Sixty-seven studies were identified from 19 countries during 1990-2017. Most assessments were performed within cognition, sensory-motor development, academic achievement or neuropsychological diagnosis. Few studies assessed other outcomes (magnetic resonance imaging, serum-biomarkers, mortality, neurological examination, measurement of head circumference, impairment of vision). Rating according to the NOS rewarded a mean of six stars out of nine. Some concerns prevail regarding potential inter-rater variability because of equivocal description of rating criteria. Specific features such as stability over lifetime and inter-relations of outcomes (e.g. prediction of subsequent development or diagnosis of neuropsychological conditions) are discussed. The importance of validity and reliability of the various test instruments are described. The studies vary immensely in important characteristics. CONCLUSIONS: Future observational studies should be more consistent in the choice of study population, age at exposure, follow-up, indication for and type of surgery, and outcomes. Assessment of sensory-motor development seems feasible in young children (age <4 yr), and intelligence/cognition in older children.

Effectiveness of tip rotation in fibreoptic bronchoscopy under different experimental conditions: an in vitro crossover study.

Background: Proper manipulation of fibreoptic bronchoscopes is essential for successful tracheal intubation or diagnostic bronchoscopy. Failure of proper navigation and rotation of the fibrescope may lead to difficulties in advancing the fibrescope and might also be responsible for (unnecessary) difficulties and delays in fibreoptic tracheal intubation, with subsequent hypoxaemia. The present study, therefore, aimed to assess the effectiveness of tip rotation in flexible bronchoscopes in different experimental conditions. Methods: Five differently sized pairs of fibrescopes (outer diameters of 2.2, 2.4, 3.5, 4.2, and 5.2 mm) were inserted into paediatric airway manikins via an appropriately sized laryngeal mask and were turned clockwise or anticlockwise at the fibrescope body or cord to 45, 90, and 180°, with the cord held either straight or bent. The primary outcome measure was the ratio of rotation measured at the tip over the rotation performed with the fibrescope body or cord. Results: Overall, the 'body' turn was significantly less effective when a bent cord was present (mean difference ranging from 29.8% (95% confidence interval 8.8-50.9) to 117.4% (93.6-141.2). This difference was diminished when the 'cord' turn was performed. Smaller fibrescopes, with outer diameters of 2.2 and 2.4 mm, were inferior with respect to the transmission of 'body' rotation to the tip. Conclusions: 'Cord' turning of the fibrescope appears to be more effective in rotating the tip than a turn of the fibrescope 'body' only. Straightening the fibrescope cord and combined 'body' and 'cord' turning are recommended.

Children's disengagement from cancer care and treatment on the ward: an undesirable social tactic in the long term.

This anthropological study explores children's non-social reactions during the active treatment period, the on-treatment, in a paediatric oncology ward in a Danish university hospital. It is argued that, although some children's non-social reactions is a tactical disengagement to manage the on-treatment situation, such non-social tactics might ultimately prove an undesirable strategy with negative long-term social consequences for social survivorship. Data were generated over 7 months of ethnographic fieldwork between May 2011 and January 2013, using qualitative methods such as participant observation and open-ended interviewing. Fifty children of both sexes between 4 and 15 years, their families and hospital staff participated in the study. These data formed the basis for the study. The findings show that children's response to care challenges, including exhaustion from care management, exposure from being in a public space, and the open-ended duration of treatment, configure in tactic forms that we term social disengagement. It is suggested that such tactical social disengagement might expand into long-term social patterns, and, as such, change from an alleviating tactic to a socially isolating and damaging tactic for survivors of cancer in childhood.

Cryopreservation of ovarian tissue for fertility preservation in a large cohort of young girls: focus on pubertal development.

STUDY QUESTION: Is there an association between the need for medical puberty induction and the diagnosis or treatment received in girls who have undergone cryopreservation of ovarian tissue for fertility preservation? SUMMARY ANSWER: There was a clear association between the intensity of treatment received and requirement for medical puberty induction but no association with the diagnosis. WHAT IS KNOWN ALREADY: Although it cannot be predicted which girls will become infertile or develop premature ovarian insufficiency (POI) following intensive chemotherapy or irradiation, patients who are at high risk of POI should be offered ovarian tissue cryopreservation (OTC). This includes girls who are planned to receive either high doses of alkylating agents, conditioning regimen before stem cell transplantation (SCT), total body irradiation (TBI) or high radiation doses to the craniospinal, abdominal or pelvic area. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort study. In total, 176 Danish girls under 18 years of age have had OTC performed over a period of 15 years. An overview of the girls' diagnoses and mean age at OTC as well as the number of deceased is presented. Of the 176 girls, 38 had died and 46 girls were still younger than 12 years so their pubertal development cannot be evaluated yet. For the 60 girls who had OTC performed after 12 years of age, the incidence of POI was evaluated and in the group of 32 girls who were younger than 12 years at OTC, the association between the diagnosis and received treatment and the requirement for medical puberty induction was examined. PARTICIPANTS/MATERIALS, SETTING, METHODS: The need for medical puberty induction was assessed in 32 girls who were prepubertal at the time of OTC. MAIN RESULTS AND THE ROLE OF CHANCE: Indications for OTC were allogeneic SCT for leukaemia, myelodysplastic syndrome or benign haematological disorders, autologous SCT for lymphoma or sarcoma, and irradiation to the pelvis or to the spinal axis. The mean age at OTC of the 176 girls were 11.3 years. The two most prevalent diagnoses of the 176 girls were malignant tumours and malignant haematological diseases. Among the 32 prepubertal girls, 12 received high dose chemotherapy and either TBI prior to SCT or irradiation to the pelvis, abdomen or the spinal axis, 13 received high dose alkylating agents but no irradiation prior to SCT, six received alkylating agents as part of conventional chemotherapy and one patient had a genetic metabolic disorder and did not receive gonadotoxic treatment. Among these 32 girls, 23 did not undergo puberty spontaneously and thus received medical puberty induction. Among the nine girls, who went through spontaneous puberty, four had received high dose alkylating agents and five had received conventional chemotherapy. LIMITATIONS REASONS FOR CAUTION: All information was retrieved retrospectively from patient records, and thus some information was not available. WIDER IMPLICATIONS OF THE FINDINGS: OTC should be recommended to all young girls, who present a high risk of developing ovarian insufficiency and/or infertility following high dose chemotherapy and/or irradiation. STUDY FUNDING/COMPETING INTERESTS: The Childhood Cancer Foundation (2012-2016) and the EU interregional project ReproHigh are thanked for having funded this study. They had no role in the study design, collection and analysis of the data or writing of the report. The authors have no conflict of interest to disclose.

No effect of anti-inflammatory medication on postprandial and postexercise muscle protein synthesis in elderly men with slightly elevated systemic inflammation.

BACKGROUND: Based on circulating C-reactive protein (CRP) levels, some individuals develop slightly increased inflammation as they age. In elderly inflamed rats, the muscle response to protein feeding is impaired, whereas it can be maintained by treatment with non-steroidal anti-inflammatory drugs (NSAIDs). It is unknown whether this applies to elderly humans with increased inflammation. Thus, the muscle response to whey protein bolus ingestion with and without acute resistance exercise was compared between healthy elderly individuals and elderly individuals with slightly increased inflammation±NSAID treatment. METHODS: Twenty-four elderly men (>60years) were recruited. Of those, 14 displayed a slightly increased systemic inflammation (CRP>2mg/l) and were randomly assigned to NSAID (Ibuprofen 1800mg/day) or placebo treatment for 1week. The remaining 10 elderly individuals served as healthy controls (CRP<1mg/l). The muscle protein synthetic response was measured as the fractional synthetic rate (FSR) and p70S6K phosphorylation-to-total protein ratio. RESULTS: The basal myofibrillar FSR and the myofibrillar FSR responses to whey protein bolus ingestion with and without acute resistance exercise were maintained in inflamed elderly compared to healthy controls (p>0.05) and so was p70S6K phosphorylation. Moreover, NSAID treatment did not significantly improve the myofibrillar and connective tissue FSR responses or reduce the plasma CRP level in inflamed, elderly individuals (p>0.05). CONCLUSION: A slight increase in systemic inflammation does not affect the basal myofibrillar FSR or the myofibrillar FSR responses, which suggests that elderly individuals with slightly increased inflammation can benefit from protein ingestion and resistance exercise to stimulate muscle protein anabolism. Moreover, the NSAID treatment did not significantly affect the myofibrillar or connective tissue FSR responses to protein ingestion and acute resistance exercise.

Gene expression risk signatures maintain prognostic power in multiple myeloma despite microarray probe set translation.

INTRODUCTION: Gene expression profiling (GEP) risk models in multiple myeloma are based on 3'-end microarrays. We hypothesized that GEP risk signatures could retain prognostic power despite being translated and applied to whole-transcript microarray data. METHODS: We studied CD138-positive bone marrow plasma cells in a prospective cohort of 59 samples from newly diagnosed patients eligible for high-dose therapy (HDT) and 67 samples from previous HDT patients with progressive disease. We used Affymetrix Human Gene 1.1 ST microarrays for GEP. Nine GEP risk signatures were translated by probe set match and applied to our data in multivariate Cox regression analysis for progression-free survival and overall survival in combination with clinical, cytogenetic and biochemical risk markers, including the International Staging System (ISS). RESULTS: Median follow-up was 66 months (range 42-87). Various translated GEP risk signatures or combinations hereof were significantly correlated with survival: among newly diagnosed patients mainly in combination with cytogenetic high-risk markers and among relapsed patients mainly in combination with ISS stage III. CONCLUSION: Translated GEP risk signatures maintain significant prognostic power in HDT myeloma patients. We suggest probe set matching for GEP risk signature translation as part of the efforts towards a microarray-independent GEP risk standard. (ClicinalTrials.gov identifier: NCT00639054).

Burnout syndrome among psychiatric trainees in 22 countries: Risk increased by long working hours, lack of supervision, and psychiatry not being first career choice.

BACKGROUND: Postgraduate medical trainees experience high rates of burnout, but evidence regarding psychiatric trainees is missing. We aim to determine burnout rates among psychiatric trainees, and identify individual, educational and work-related factors associated with severe burnout. METHODS: In an online survey psychiatric trainees from 22 countries were asked to complete the Maslach Burnout Inventory (MBI-GS) and provide information on individual, educational and work-related parameters. Linear mixed models were used to predict the MBI-GS scores, and a generalized linear mixed model to predict severe burnout. RESULTS: This is the largest study on burnout and training conditions among psychiatric trainees to date. Complete data were obtained from 1980 out of 7625 approached trainees (26%; range 17.8-65.6%). Participants were 31.9 (SD 5.3) years old with 2.8 (SD 1.9) years of training. Severe burnout was found in 726 (36.7%) trainees. The risk was higher for trainees who were younger (P<0.001), without children (P=0.010), and had not opted for psychiatry as a first career choice (P=0.043). After adjustment for socio-demographic characteristics, years in training and country differences in burnout, severe burnout remained associated with long working hours (P<0.001), lack of supervision (P<0.001), and not having regular time to rest (P=0.001). Main findings were replicated in a sensitivity analysis with countries with response rate above 50%. CONCLUSIONS: Besides previously described risk factors such as working hours and younger age, this is the first evidence of negative influence of lack of supervision and not opting for psychiatry as a first career choice on trainees' burnout.

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial.

Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT and median OS was almost 5.5 years with acceptable toxicity. A recent prospective randomized study confirms salvage ASCT to be an effective treatment.