Contemporary outcomes of left thoraco-abdominal esophagectomy due to cancer in the esophagus or gastroesophageal junction, a multicenter cohort study.

Surgery for cancer of the esophagus or gastro-esophageal junction can be performed with a variety of minimally invasive and open approaches. The left thoracoabdominal esophagectomy (LTE) is an open technique that gives an opportunity to operate in the chest and abdomen with excellent exposure of the gastro-esophageal junction through a single incision, and there is currently no equivalent minimally invasive technique available. The aim of this multi-institutional review was to study a large contemporary international study cohort of patients treated with LTE. An international multicenter cohort study was performed including all patients treated with LTE at six high-volume centers for gastro-esophageal cancer surgery between 2012 and 2022. Patient data were prospectively collected in each participating centers' institutional database. Information about patient, tumor, and treatment details were collected. The study cohort included a total of 793 patients treated with LTE during the study period. The most frequently observed complications were pneumonia in 185/727 (25.5%) patients and atrial fibrillation in 91/727 (12.5%). Anastomotic leak occurred in 35/727 (4.8%) patients; no patient suffered from conduit necrosis. Thirty-day mortality occurred in 15/785 (1.9%) patients and 90-day mortality in 39/785 (5.0%) patients. Factors with statistically significant association with survival were American Society for Anesthesiologists-score, tumor location, tumor stage, and tumor free resection margins. Neoadjuvant therapy was not associated with increased survival compared to surgery alone but neoadjuvant chemoradiotherapy compared to neoadjuvant chemotherapy showed statistically significant improved survival with hazard ratio 0.60 (95% confidence intervals:0.44-0.80, P = 0.001) in a multivariable adjusted model. This study demonstrates that LTE can be applied in selected patients with results that are comparable to other large studies of open and minimally invasive surgery for esophageal or gastro-esophageal cancer at high-volume centers.

Open left thoracoabdominal esophagectomy a viable option in the era of minimally invasive esophagectomy.

Minimally invasive surgical technique has become standard at many institutions in esophageal cancer surgery. In some situations, however other surgical approaches are required. Left thoracoabdominal esophagectomy (LTE) facilitates complete resection of esophageal cancer particularly for bulky distal esophageal tumors, but there are concerns that this approach is associated with significant morbidity. Prospectively entered esophagectomy databases from three high-volume centers were reviewed for patients undergoing LTE or MIE 2009-2019. Patient demographics, tumor characteristics, operative outcomes, postoperative outcomes, and pathologic surrogates of oncologic efficacy (R0 resection rate, and number of resected lymph nodes) were compared. In total 915 patients were included in the study, LTE was applied in 684 (74.8%) patients, and MIE in 231 (25.2%) patients. LTE patients had more locally advanced tumor stage and received more neoadjuvant treatment. Patients treated with MIE had more comorbidities. The results showed no difference in overall postoperative complications (LTE = 61.7%, MIE = 65.7%, P = 0.289), severe complications (Clavien-Dindo ≥IIIa (LTE = 25.9%, MIE 26.8%, P = 0.806)), pneumonia (LTE = 29.0%, MIE = 24.7%, P = 0.211), anastomotic leak (LTE = 7.8%, MIE = 11.3%, P = 0.101), or in-hospital mortality (LTE = 2.6%, MIE = 3.5%, P = 0.511). Median number of resected lymph nodes was 24 for LTE and 25 for MIE (P = 0.491). LTE was used for more advanced tumors in patients that were more likely to have received neoadjuvant treatment compared with MIE, however postoperative morbidity, mortality, and oncologic outcomes were equivalent to that of MIE in this cohort. In conclusion open resection with left thoracoabdominal approach is a valid option in selected patients when performed at high-volume esophagectomy centers.

Pulmonary Arterial Pruning and Longitudinal Change in Percent Emphysema and Lung Function: The Genetic Epidemiology of COPD Study.

BACKGROUND: Pulmonary endothelial damage has been shown to precede the development of emphysema in animals, and vascular changes in humans have been observed in COPD and emphysema. RESEARCH QUESTION: Is intraparenchymal vascular pruning associated with longitudinal progression of emphysema on CT imaging or decline in lung function over 5 years? STUDY DESIGN AND METHODS: The Genetic Epidemiology of COPD Study enrolled ever smokers with and without COPD from 2008 through 2011. The percentage of emphysema-like lung, or "percent emphysema," was assessed at baseline and after 5 years on noncontrast CT imaging as the percentage of lung voxels < -950 Hounsfield units. An automated CT imaging-based tool assessed and classified intrapulmonary arteries and veins. Spirometry measures are postbronchodilator. Pulmonary arterial pruning was defined as a lower ratio of small artery volume (< 5 mm2 cross-sectional area) to total lung artery volume. Mixed linear models included demographics, anthropomorphics, smoking, and COPD, with emphysema models also adjusting for CT imaging scanner and lung function models adjusting for clinical center and baseline percent emphysema. RESULTS: At baseline, the 4,227 participants were 60 ± 9 years of age, 50% were women, 28% were Black, 47% were current smokers, and 41% had COPD. Median percent emphysema was 2.1 (interquartile range, 0.6-6.3) and progressed 0.24 percentage points/y (95% CI, 0.22-0.26 percentage points/y) over 5.6 years. Mean FEV1 to FVC ratio was 68.5 ± 14.2% and declined 0.26%/y (95% CI, -0.30 to -0.23%/y). Greater pulmonary arterial pruning was associated with more rapid progression of percent emphysema (0.11 percentage points/y per 1-SD increase in arterial pruning; 95% CI, 0.09-0.16 percentage points/y), including after adjusting for baseline percent emphysema and FEV1. Arterial pruning also was associated with a faster decline in FEV1 to FVC ratio (-0.04%/y per 1-SD increase in arterial pruning; 95% CI, -0.008 to -0.001%/y). INTERPRETATION: Pulmonary arterial pruning was associated with faster progression of percent emphysema and more rapid decline in FEV1 to FVC ratio over 5 years in ever smokers, suggesting that pulmonary vascular differences may be relevant in disease progression. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Central nervous system relapse in high-risk stage 4 neuroblastoma: The HR-NBL1/SIOPEN trial experience.

BACKGROUND: There is rising concern on the impact of new strategies, such as high-dose chemotherapy (HDC) and immunotherapy, on the pattern of relapse in high-risk neuroblastoma (HR-NBL). Our aim is to evaluate the incidence and identify risk factors for first recurrence in the central nervous system (CNS) in HR-NBL. PATIENTS AND METHODS: Data from patients with stage 4V HR-NBL included from February 2002 to June 2015 in the prospective HR-NBL trial of the European International Society of Pediatric Oncology Neuroblastoma Group were analysed. Characteristics at diagnosis, treatment and the pattern of first relapse were studied. CNS imaging at relapse was centrally reviewed. RESULTS: The 1977 included patients had a median age of 3 years (1 day-20 years); 1163 were boys. Among the 1161 first relapses, 53 were in the CNS, with an overall incidence of 2.7%, representing 6.2% of all metastatic relapses. One- and three-year post-relapse overall survival was 25 ± 6% and 8 ± 4%, respectively. Higher risk of CNS recurrence was associated with female sex (hazard ratio [HR] = 2.0 [95% confidence interval {CI}: 1.1-3.5]; P = 0.016), MYCN-amplification (HR = 2.4 [95% CI: 1.2-4.4]; P = 0.008), liver (HR = 2.5 [95% CI: 1.2-5.1]; P = 0.01) or >1 metastatic compartment involvement (HR = 7.1 [95% CI: 1.0-48.4]; P = 0.047) at diagnosis. Neither HDC nor immunotherapy was associated with higher risk of CNS recurrence. Stable incidence of CNS relapse was reported over time. CONCLUSIONS: The risk of CNS recurrence is linked to both patient and disease characteristics, with neither impact of HDC nor immunotherapy. These findings support the current treatment strategy and do not justify a CNS prophylactic treatment.

Impact on postoperative complications of changes in skeletal muscle mass during neoadjuvant chemotherapy for gastro-oesophageal cancer.

BACKGROUND: Risk assessment is relevant to predict postoperative outcomes in patients with gastro-oesophageal cancer. This cohort study aimed to assess body composition changes during neoadjuvant chemotherapy and investigate their association with postoperative complications. METHODS: Consecutive patients with gastro-oesophageal cancer undergoing neoadjuvant chemotherapy and surgery with curative intent between 2016 and 2019 were identified from a specific database and included in the study. CT images before and after neoadjuvant chemotherapy were used to assess the skeletal muscle index, sarcopenia, and subcutaneous and visceral fat index. RESULTS: In a cohort of 199 patients, the mean skeletal muscle index decreased during neoadjuvant therapy (from 51·187 to 49·19 cm2 /m2 ; P < 0·001) and the rate of sarcopenia increased (from 42·2 to 54·3 per cent; P < 0·001). A skeletal muscle index decrease greater than 5 per cent was not associated with an increased risk of total postoperative complications (odds ratio 0·91, 95 per cent c.i. 0·52 to 1·59; P = 0·736) or severe complications (odds ratio 0·66, 0·29 to 1·53; P = 0·329). CONCLUSION: Skeletal muscle index decreased during neoadjuvant therapy but was not associated with postoperative complications.

ANTECEDENTES: La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea. RESULTADOS: En una cohorte de 199 pacientes, el índice de masa muscular esquelética disminuyó durante el tratamiento neoadyuvante (de 51,87 cm2 /m2 a 49,19 cm2 /m2 , P < 0,001) y las tasas de sarcopenia aumentaron (de 42,2% a 54,2%, P < 0,001). Una disminución del índice de masa muscular esquelética > 5% no se asoció con un mayor riesgo de complicaciones postoperatorias globales (razón de oportunidades, odds ratio: 0,908; ic. del 95%: 0,520-1,587, P = 0,736) ni de complicaciones graves (odds ratio: 0,661; i.c. del 95%: 0,286-1,525, P = 0,329). CONCLUSIÓN: El índice de masa muscular esquelética disminuyó durante el tratamiento neoadyuvante, pero no se asoció con complicaciones postoperatorias.

International standards for fetal brain structures based on serial ultrasound measurements from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project.

OBJECTIVE: To create prescriptive growth standards for five fetal brain structures, measured using ultrasound, in healthy, well-nourished women at low risk of impaired fetal growth and poor perinatal outcome, taking part in the Fetal Growth Longitudinal Study (FGLS) of the INTERGROWTH-21st Project. METHODS: This was a complementary analysis of a large, population-based, multicenter, longitudinal study. The sample analyzed was selected randomly from the overall FGLS population, ensuring an equal distribution among the eight diverse participating sites and of three-dimensional (3D) ultrasound volumes across pregnancy (range: 15-36 weeks' gestation). We measured, in planes reconstructed from 3D ultrasound volumes of the fetal head at different timepoints in pregnancy, the size of the parieto-occipital fissure (POF), Sylvian fissure (SF), anterior horn of the lateral ventricle, atrium of the posterior horn of the lateral ventricle (PV) and cisterna magna (CM). Fractional polynomials were used to construct the standards. Growth and development of the infants were assessed at 1 and 2 years of age to confirm their adequacy for constructing international standards. RESULTS: From the entire FGLS cohort of 4321 women, 451 (10.4%) were selected at random. After exclusions, 3D ultrasound volumes from 442 fetuses born without a congenital malformation were used to create the charts. The fetal brain structures of interest were identified in 90% of cases. All structures, except the PV, showed increasing size with gestational age, and the size of the POF, SF, PV and CM showed increasing variability. The 3rd , 5th , 50th , 95th and 97th smoothed centiles are presented. The 5th centiles for the POF and SF were 3.1 mm and 4.7 mm at 22 weeks' gestation and 4.6 mm and 9.9 mm at 32 weeks, respectively. The 95th centiles for the PV and CM were 8.5 mm and 7.5 mm at 22 weeks and 8.6 mm and 9.5 mm at 32 weeks, respectively. CONCLUSIONS: We have produced prescriptive size standards for fetal brain structures based on prospectively enrolled pregnancies at low risk of abnormal outcome. We recommend these as international standards for the assessment of measurements obtained using ultrasound from fetal brain structures. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Image-scoring system for umbilical and uterine artery pulsed-wave Doppler ultrasound measurement.

OBJECTIVES: To develop an objective image-scoring system for pulsed-wave Doppler measurement of maternal uterine and fetal umbilical arteries, and evaluate how this compares with subjective assessment. METHODS: As an extension to the INTERGROWTH-21st Project, we developed a scoring system based on six predefined criteria for uterine and umbilical artery pulsed-wave Doppler measurements. Objective evaluation using the scoring system was compared with subjective assessment which consisted of classifying an image as simply acceptable or unacceptable. Based on sample size estimation, a total of 120 umbilical and uterine artery Doppler images were selected randomly from the INTERGROWTH-21st image database. Two independent reviewers evaluated all images in a blinded fashion, both subjectively and using the six-point scoring system. Percentage agreement and kappa statistic were compared between the two methods. RESULTS: The overall agreement between reviewers was higher for objective assessment using the scoring system (agreement, 85%; adjusted kappa, 0.70) than for subjective assessment (agreement, 70%; adjusted kappa, 0.47). For the six components of the scoring system, the level of agreement (adjusted kappa) was 0.97 for anatomical site, 0.88 for sweep speed, 0.77 for magnification, 0.68 for velocity scale, 0.68 for image clarity and 0.65 for angle of insonation. CONCLUSION: In quality assessment of umbilical and uterine artery pulsed-wave Doppler measurements, our proposed objective six-point image-scoring system is associated with greater reproducibility than is subjective assessment. We recommend this as the preferred method for quality control, auditing and teaching. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Quality control of ultrasound for fetal biometry: results from the INTERGROWTH-21st Project.

OBJECTIVE: To assess a comprehensive package of ultrasound quality control in the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project, a large multicenter study of fetal growth. METHODS: Quality control (QC) measures were performed for 20 313 ultrasound scan images obtained prospectively from 4321 fetuses at 14-41 weeks' gestation in eight geographical locations. At the time of each ultrasound examination, three fetal biometric variables (head circumference (HC), abdominal circumference (AC) and femur length (FL)) were measured in triplicate on separately generated images. All measurements were taken in a blinded fashion. QC had two elements: (1) qualitative QC: visual assessment by sonographers at each study site of their images based on specific criteria, with 10% of images being re-assessed at the Oxford-based Ultrasound Quality Unit (compared using an adjusted kappa statistic); and (2) quantitative QC: assessment of measurement data by comparing the first, second and third measurements (intraobserver variability), remeasurement of caliper replacement in 10% (interobserver variability), both by Bland-Altman plots and plotting frequency histograms of the SD of triplicate measurements and assessing how many were above or below 2 SD of the expected distribution. The system allowed the sonographers' performances to be monitored regularly. RESULTS: A high level of agreement between self- and external scoring was demonstrated for all measurements (κ = 0.99 (95% CI, 0.98-0.99) for HC, 0.98 (95% CI, 0.97-0.99) for AC and 0.96 (95% CI, 0.95-0.98) for FL). Intraobserver 95% limits of agreement (LoA) of ultrasound measures for HC, AC and FL were ± 3.3%, ± 5.6% and ± 6.2%, respectively; the corresponding values for interobserver LoA were ± 4.4%, ± 6.0% and ± 5.6%. The SD distribution of triplicate measurements for all biometric variables showed excessive variability for three of 31 sonographers, allowing prompt identification and retraining. CONCLUSIONS: Qualitative and quantitative QC monitoring was feasible and highly reproducible in a large multicenter research study, which facilitated the production of high-quality ultrasound images. We recommend that the QC system we developed is implemented in future research studies and clinical practice. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Optimizing the process of fertility preservation in pediatric female cancer patients - a multidisciplinary program.

BACKGROUND: Current evidence indicates sub-optimal incidence of fertility preservation (FP) in eligible patients. We present herein our designated multidisciplinary program for FP in pediatric and adolescent population and present our data on FP in female patients. METHODS: Pediatric patients (age 0-18) who were candidate for highly gonadotoxic treatments were referred to FP program for a multidisciplinary discussion and gonadal risk-assessment followed by either oocyte cryopreservation or ovarian cryopreservation (OCP) for female patients, and sperm banking for male patients. The OCP protocol consists of aspiration of oocytes from small antral follicles and in-vitro maturation followed by cryopreservation, as well as ovarian tissue cryopreservation. RESULTS: The establishment of a designated FP program resulted in a significant increase in referral and subsequent FP procedures of all eligible patients. Sixty-two female patients were referred for FP discussion during a period of 36 months; 41 underwent OCP; 11 underwent oocyte cryopreservation and six were declined due to parental decision. The median age was 13.2y (range 18 months-18y). Thirty-two (51.6 %) were chemotherapy-naïve. Seventeen patients (27 %) had sarcoma, 16 patients (26 %) had acute leukemia. The mean number of mature oocytes that were eventually vitrified was significantly higher in chemotherapy-naïve patients compared with chemotherapy-exposed patients (mean 12 oocytes (1-42) versus 2 (0-7)). CONCLUSION: Multidisciplinary programs that encompass experts of all relevant fields, skilled laboratory resources and a facilitated path appear to maximize the yield. We observed a considerable higher referral rates following launching a designated program and earlier OCP in chemo-naïve patients that culminated in a better fertility preservation procedure.

Cryopreservation of in vitro matured oocytes in addition to ovarian tissue freezing for fertility preservation in paediatric female cancer patients before and after cancer therapy.

STUDY QUESTION: Is a protocol that combines in vitro maturation of germinal vesicle-stage oocytes and their vitrification with freezing of cortical ovarian tissue feasible for use in fertility preservation for both chemotherapy-naive paediatric patients as well as patients after initiation of cancer therapy? SUMMARY ANSWER: Follicle-containing ovarian tissue as well as oocytes that can undergo maturation in vitro can be obtained from paediatric patients (including prepubertal girls) both before and after cancer therapy. WHAT IS KNOWN ALREADY: Anticancer therapy reduces the number of follicles/oocytes but this effect is less severe in young patients, particularly the paediatric age group. Autotransplantation of ovarian tissue has yielded to date 60 live births, including one from tissue that was cryostored in adolescence. However, it is assumed that autografting cryopreserved-thawed ovarian cortical tissue poses a risk of reseeding the malignancy. Immature oocytes can be collected from very young girls without hormonal stimulation and then matured in vitro and vitrified. We have previously shown that there is no difference in the number of ovarian cortical follicles between paediatric patients before and after chemotherapy. STUDY DESIGN, SIZE, DURATION: A prospective study was conducted in a cohort of 42 paediatric females with cancer (before and after therapy initiation) who underwent fertility preservation procedures in 2007-2014 at a single tertiary medical centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: The study group included girls and adolescent females with cancer: 22 before and 20 after chemotherapy. Following partial or complete oophorectomy, immature oocytes were either aspirated manually ex vivo from visible small antral follicles or filtered from spent media. Oocytes were incubated in oocyte maturation medium, and those that matured at 24 or 48 h were vitrified. Ovarian cortical tissue was cut and prepared for slow-gradual cryopreservation. Anti-Mullerian hormone (AMH) levels were measured in serum before and after oophorectomy. MAIN RESULTS AND ROLE OF CHANCE: Ovarian tissue was successfully collected from 78.7% of the 42 patients. Oocytes were obtained from 20 patients before chemotherapy and 13 after chemotherapy. The youngest patients from whom oocytes were retrieved were aged 2 years (two atretic follicles) and 3 years. Of the 395 oocytes collected, ∼30% were atretic (29.6% in the pre-chemotherapy group, 37% in the post-chemotherapy group). One hundred twenty-one oocytes (31%) were matured in vitro and vitrified: 67.8% from patients before chemotherapy, the rest after chemotherapy. Mature oocytes suitable for vitrification were obtained from 16/20 patients before chemotherapy and from 12/13 patients after chemotherapy (maturation rate, 32 and 26.4%, respectively). There were significant correlations of the number of vitrified oocytes with patient age (more matured oocytes with older age) (P = 0.001) and with pre-oophorectomy AMH levels (P = 0.038 pre-chemotherapy group, P = 0.029 post-chemotherapy group). Oocytes suitable for vitrification were obtained both by manual aspiration of antral follicles (45%) and from rinse solutions after dissection. There were significantly more matured oocytes in the pre-chemotherapy group from aspiration than in the post-chemotherapy group after both aspiration (P < 0.033) and retrieval from rinsing fluids (P < 0.044). The number of pre-antral follicles per histological section did not differ in the pre- versus post-chemotherapy. AMH levels dropped by approximately 50% after ovarian removal in both groups, with a significant correlation between pre- and post-oophorectomy levels (P = 0.002 pre-chemotherapy group, P = 0.001 post-chemotherapy group). LIMITATIONS, REASONS FOR CAUTION: There were no patients between 5 years and 10 years old in the post-chemotherapy group, which might have affected some results and correlations. Oocytes from patients soon after chemotherapy might be damaged, and caution is advised when using them for fertility-restoration purposes. The viability, development capability and fertilization potential of oocytes from paediatric patients, especially prepubertal and after chemotherapy, are unknown, in particular oocytes recovered from the media after the tissue dissection step. WIDER IMPLICATIONS OF THE FINDINGS: Although more oocytes were collected and matured from chemotherapy-naïve paediatric patients, ovarian tissue and immature oocytes were also retrieved from young girls in whom cancer therapy has already been initiated. Our centre has established a protocol for potential maximal fertility preservation in paediatric female patients with cancer. Vitrified-in vitro-matured oocytes may serve as an important gamete source in paediatric female patients with cancer because the risk of reseeding the disease is avoided. Further studies are needed on the fertility-restoring potential of oocytes from paediatric and prepubertal patients, especially after exposure to chemotherapy. STUDY FUNDING/COMPETING INTERESTS: The study was conducted as part of the routine procedures for fertility preservation at our IVF unit. No funding outside of the IVF laboratory was received. Funding for the AMH measurements was obtained by a research grant from the Israel Science Foundation (to B.-A.I., ISF 13-1873). None of the authors have competing interests. TRIAL REGISTRATION NUMBER: N/A.

A randomised controlled trial using the Epidrum for labour epidurals.

The aim of our study was to determine if using the Epidrum to site epidurals improves success and reduces morbidity. Three hundred parturients requesting epidural analgesia for labour were enrolled. 150 subjects had their epidural sited using Epidrum and 150 using standard technique. We recorded subject demographics, operator experience, number of attempts, Accidental Dural Puncture rate, rate of failure to site epidural catheter, rate of failure of analgesia, Post Dural Puncture Headache and Epidural Blood Patch rates. Failure rate in Epidrum group was 9/150 (6%) vs 0 (0%) in the Control group (P = 0.003). There were four (2.66%) accidental dural punctures in the Epidrum group and none in the Control group (P = 0.060), and 2 epidurals out of 150 (1.33%) in Epidrum group were re-sited, versus 3/150 (2%) in the control group (P = 1.000). The results of our study do not suggest that using Epidrum improves success or reduces morbidity.

Serum 25-hydroxy vitamin D concentrations are more deficient/insufficient in peritoneal dialysis than haemodialysis patients in a sunny climate.

BACKGROUND: Research has identified associations between serum 25(OH)D and a range of clinical outcomes in chronic kidney disease and wider populations. The present study aimed to investigate vitamin D deficiency/insufficiency in dialysis patients and the relationship with vitamin D intake and sun exposure. METHODS: A cross-sectional study was used. Participants included 30 peritoneal dialysis (PD) (43.3% male; 56.87 ± 16.16 years) and 26 haemodialysis (HD) (80.8% male; 63.58 ± 15.09 years) patients attending a department of renal medicine. Explanatory variables were usual vitamin D intake from diet/supplements (IU day(-1) ) and sun exposure (min day(-1) ). Vitamin D intake, sun exposure and ethnic background were assessed by questionnaire. Weight, malnutrition status and routine biochemistry were also assessed. Data were collected during usual department visits. The main outcome measure was serum 25(OH)D (nm). RESULTS: Prevalence of inadequate/insufficient vitamin D intake differed between dialysis modality, with 31% and 43% found to be insufficient (<50 nm) and 4% and 33% found to be deficient (<25 nm) in HD and PD patients, respectively (P < 0.001). In HD patients, there was a correlation between diet and supplemental vitamin D intake and 25(OH)D (ρ = 0.84, P < 0.001) and average sun exposure and 25(OH)D (ρ = 0.50, P < 0.02). There were no associations in PD patients. The results remained significant for vitamin D intake after multiple regression, adjusting for age, gender and sun exposure. CONCLUSIONS: The results highlight a strong association between vitamin D intake and 25(OH)D in HD but not PD patients, with implications for replacement recommendations. The findings indicate that, even in a sunny climate, many dialysis patients are vitamin D deficient, highlighting the need for exploration of determinants and consequences.

Xenon decreases cell migration and secretion of a pro-angiogenesis factor in breast adenocarcinoma cells: comparison with sevoflurane.

BACKGROUND: While volatile agents have been implicated in metastasis-enhancing effects on cancer cells, the effects of xenon are unknown. We investigated xenon- and sevoflurane-mediated effects on migration and expression of angiogenesis biomarkers in human breast adenocarcinoma cells. METHODS: MDA-MB-231 and MCF-7 cells were exposed to xenon 70% with O2 25%, CO2 5%; control gas containing O2 25%, CO2 5%, N2 70%; or sevoflurane 2.5 vol% administered in O2 60%, N2 37%, or control gas. Cell viability was determined by the MTT assay. Migration at 24 h was determined using the Oris™ Cell Migration Assay. Secretion of angiogenesis factors was measured using a membrane-based immunoassay array. RESULTS: Xenon reduced MDA-MB-231 migration to 59 (13%) after 1-h exposure (P=0.02), 64 (10%) after 3 h (P=0.01), and 71 (9%) after 5 h (P=0.04) compared with control gas, without affecting viability. Similarly, MCF-7 migration was significantly reduced at all timepoints [to 58 (12%) at 1 h, 65 (12%) at 3 h, and 65% (12%) at 5 h]. Sevoflurane did not affect migration when delivered in control gas. Glycine, an N-methyl-d-aspartate receptor co-agonist, antagonized the effects of xenon on migration. Expression of the pro-angiogenesis factor regulated on activation, normal T cell expressed and secreted (RANTES) was reduced in conditioned medium from xenon-exposed MDA-MB-231 cells compared with cells exposed to either control gas or sevoflurane [mean dot density 2.0 (0.2) compared with 3.0 (0.1) and 3.1 (0.3), respectively (P=0.02)]. CONCLUSION: Xenon, but not sevoflurane, inhibited migration in both oestrogen receptor positive and negative breast adenocarcinoma cells. Furthermore, xenon decreased release of the pro-angiogenic factor RANTES from MDA-MB-231 cells.

Negative selection by apoptosis enriches progenitors in naïve and expanded human umbilical cord blood grafts.

The influence of TNF-α and Fas-ligand (FasL) on viability and function was evaluated in fresh- and expanded-umbilical cord blood (UCB) cells. CD34(+) progenitors and T cells display outstanding survival, whereas ~30% and >50% B lymphocytes and myeloid cells undergo spontaneous apoptosis within 24 and 48 h, respectively. Although the impact of exposure to toxic doses of FasL and TNF-α was undetectable in measurements of apoptosis; removal of dead cells after 2 days of incubation with the ligands revealed a twofold increase in frequency of colony-forming cells (CFU). The sensitivity of progenitors to apoptosis was also unaffected by Fas cross-linking following TNF-induced upregulation of the receptor, increasing CFU frequency without impairing SCID repopulating cell (SRC) activity. Most significant enrichment in CD34(+) progenitors and corresponding increase in CFU frequency were observed when FasL was applied during the final week of ex vivo expansion under the influence of nicotinamide, without impairing SRC activity. These data emphasize differential sensitivities of UCB progenitors and lineage-positive cells to apoptotic signaling mediated by the Fas and TNF receptors, which might be useful in improving the efficiency of ex vivo expansion and improving UCB cell engraftment.

Apoptotic signaling through Fas and TNF receptors ameliorates GVHD in mobilized peripheral blood grafts.

Mobilized peripheral blood (mPB) is a prevalent source of hematopoietic progenitors for transplantation; however, allogeneic and haploidentical transplants are often accompanied by severe GVHD. Following the observation that murine GVHD is ameliorated by pretransplant donor cell exposure to Fas-ligand (FasL) without host-specific sensitization, we assessed the susceptibility of mPB cells to spontaneous and receptor-induced apoptosis as a possible approach to GVHD prophylaxis. Short incubation for 4 h resulted in spontaneous apoptosis of 50% of the T and B lymphocytes and 60% myeloid cells. Although expression of Fas and TNF-R1 was proportionate to fractional apoptosis, cell death was dominated by spontaneous apoptosis. Functional assays revealed that the death receptors modulated mPB graft composition as compared with incubation in medium, without detectable quantitative variations. Removal of dead cells increased the frequency of mPB myeloid progenitors (P<0.001 vs medium), and recipients of mPB exposed to death ligands displayed reduced GVHD (P<0.01 vs medium) and improved survival following lipopolysacharide stimulation. mPB grafts exposed to the apoptotic challenge retained SCID reconstituting potential and graft versus tumor activity. These data emphasize that short-term exposure of mPB grafts to an apoptotic challenge is effective in reduction of GVHD effector activity.

Work-based assessment: qualitative perspectives of novice nutrition and dietetics educators.

BACKGROUND: The assessment of competence for health professionals including nutrition and dietetics professionals in work-based settings is challenging. The present study aimed to explore the experiences of educators involved in the assessment of nutrition and dietetics students in the practice setting and to identify barriers and enablers to effective assessment. METHODS: A qualitative research approach using in-depth interviews was employed with a convenience sample of inexperienced dietitian assessors. Interviews explored assessment practices and challenges. Data were analysed using a thematic approach within a phenomenological framework. Twelve relatively inexperienced practice educators were purposefully sampled to take part in the present study. RESULTS: Three themes emerged from these data. (i) Student learning and thus assessment is hindered by a number of barriers, including workload demands and case-mix. Some workplaces are challenged to provide appropriate learning opportunities and environment. Adequate support for placement educators from the university, managers and their peers and planning are enablers to effective assessment. (ii) The role of the assessor and their relationship with students impacts on competence assessment. (iii) There is a lack of clarity in the tasks and responsibilities of competency-based assessment. CONCLUSIONS: The present study provides perspectives on barriers and enablers to effective assessment. It highlights the importance of reflective practice and feedback in assessment practices that are synonymous with evidence from other disciplines, which can be used to better support a work-based competency assessment of student performance.

Anaesthesia for parturients with severe cystic fibrosis: a case series.

Cystic fibrosis affects 1 in 1600-2500 live births and is inherited in an autosomal recessive manner. It primarily involves the respiratory, gastrointestinal and reproductive tracts, with impaired clearance of, and obstruction by, increasingly viscous secretions. Severe respiratory disease, diabetes and gastro-oesophageal reflux may result. Improvements in medical management and survival of cystic fibrosis patients means more are committing to pregnancies. Although guidance for anaesthesia in this patient group is available, management and outcome data associated with more severe cases are sparse. Patients with severe cystic fibrosis require multidisciplinary input and should be managed in a tertiary referral centre. Close monitoring of respiratory function and preoperative optimisation during pregnancy are mandatory. The risk of preterm labour and delivery is increased. Pregnancy and delivery can be managed successfully, even in patients with FEV1 <40% predicted. Neuraxial anaesthesia and analgesia should be the technique of choice for delivery. Postoperative care should be carried out in a critical care setting with the provision of postoperative ventilation if necessary.

Early immunisation with dendritic cells after allogeneic bone marrow transplantation elicits graft vs tumour reactivity.

BACKGROUND: Perspectives of immunotherapy to cancer mediated by bone marrow transplantation (BMT) in conjunction with dendritic cell (DC)-mediated immune sensitisation have yielded modest success so far. In this study, we assessed the impact of DC on graft vs tumour (GvT) reactions triggered by allogeneic BMT. METHODS: H2K(a) mice implanted with congenic subcutaneous Neuro-2a neuroblastoma (NB, H2K(a)) tumours were irradiated and grafted with allogeneic H2K(b) bone marrow cells (BMC) followed by immunisation with tumour-inexperienced or tumour-pulsed DC. RESULTS: Immunisation with tumour-pulsed donor DC after allogeneic BMT suppressed tumour growth through induction of T cell-mediated NB cell lysis. Early post-transplant administration of DC was more effective than delayed immunisation, with similar efficacy of DC inoculated into the tumour and intravenously. In addition, tumour inexperienced DC were equally effective as tumour-pulsed DC in suppression of tumour growth. Immunisation of DC did not impact quantitative immune reconstitution, however, it enhanced T-cell maturation as evident from interferon-γ (IFN-γ) secretion, proliferation in response to mitogenic stimulation and tumour cell lysis in vitro. Dendritic cells potentiate GvT reactivity both through activation of T cells and specific sensitisation against tumour antigens. We found that during pulsing with tumour lysate DC also elaborate a factor that selectively inhibits lymphocyte proliferation, which is however abolished by humoral and DC-mediated lymphocyte activation. CONCLUSION: These data reveal complex involvement of antigen-presenting cells in GvT reactions, suggesting that the limited success in clinical application is not a result of limited efficacy but suboptimal implementation. Although DC can amplify soluble signals from NB lysates that inhibit lymphocyte proliferation, early administration of DC is a dominant factor in suppression of tumour growth.

Nutritional status in Parkinson's disease patients undergoing deep brain stimulation surgery: a pilot study.

OBJECTIVES: People with Parkinson's disease (PD) are at higher risk of malnutrition due to PD symptoms and pharmacotherapy side effects. When pharmacotherapy is no longer effective for symptom control, deep-brain stimulation (DBS) surgery may be considered. The aim of this study was to assess the nutritional status of people with PD who may be at higher risk of malnutrition related to unsatisfactory symptom management with optimised medical therapy. DESIGN: This was an observational study using a convenience sample. SETTING: Participants were seen during their hospital admission for their deep brain stimulation surgery. PARTICIPANTS: People with PD scheduled for DBS surgery were recruited from a Brisbane neurological clinic (n=15). MEASUREMENTS: The Patient-Generated Subjective Global Assessment (PG-SGA), weight, height and body composition were assessed to determine nutritional status. RESULTS: Six participants (40%) were classified as moderately malnourished (SGA-B). Eight participants (53%) reported previous unintentional weight loss (average loss of 13%). On average, participants classified as well-nourished (SGA-A) were younger, had shorter disease durations, lower PG-SGA scores, higher body mass (BMI) and fat free mass indices (FFMI) when compared to malnourished participants (SGA-B). Five participants had previously received dietetic advice but only one in relation to unintentional weight loss. CONCLUSION: Malnutrition remains unrecognised and untreated in this group despite unintentional weight loss and presence of nutrition impact symptoms. Improving nutritional status prior to surgery may improve surgical outcomes.

Cost effectiveness of nutrition support in the prevention of pressure ulcer in hospitals.

BACKGROUND/OBJECTIVES: This study estimates the economic outcomes of a nutrition intervention to at-risk patients compared with standard care in the prevention of pressure ulcer. SUBJECTS/METHODS: Statistical models were developed to predict 'cases of pressure ulcer avoided', 'number of bed days gained' and 'change to economic costs' in public hospitals in 2002-2003 in Queensland, Australia. Input parameters were specified and appropriate probability distributions fitted for: number of discharges per annum; incidence rate for pressure ulcer; independent effect of pressure ulcer on length of stay; cost of a bed day; change in risk in developing a pressure ulcer associated with nutrition support; annual cost of the provision of a nutrition support intervention for at-risk patients. A total of 1000 random re-samples were made and the results expressed as output probability distributions. RESULTS: The model predicts a mean 2896 (s.d. 632) cases of pressure ulcer avoided; 12, 397 (s.d. 4491) bed days released and corresponding mean economic cost saving of euros 2 869 526 (s.d. 2 078 715) with a nutrition support intervention, compared with standard care. CONCLUSION: Nutrition intervention is predicted to be a cost-effective approach in the prevention of pressure ulcer in at-risk patients.