The effect of heavy prenatal alcohol exposure on adolescent body mass index and waist-to-height ratio at 12-13 years.

BACKGROUND: Growing evidence suggests that prenatal alcohol exposure (PAE) has the potential to impact on a wide range of physical outcomes in offspring, including metabolism and body composition, although the evidence to-date is primarily from preclinical studies. The current clinical study examined the association between heavy PAE and indirect measures of adiposity in adolescence. METHODS: Analyses drew on data from the Longitudinal Study of Australian Children, a national prospective cohort of children and their families from birth to adolescence. Participants included children with heavy PAE (≥70 g/week; n = 46), measured via maternal self-report of alcohol use during pregnancy and a comparison group of children without any PAE (n = 782), frequency matched on sex, ethnicity and socio-economic position. Body mass index (BMI) z-scores, waist-to-height ratios and proportion overweight/obese were calculated from height, weight and waist circumference measured at age 12-13 years. Two (PAE) × two (sex) ANCOVA and logistic regression models were performed, controlling for matching variables, adolescent age, pubertal status and birthweight; maternal age at birth and smoking during pregnancy. RESULTS: Female adolescents with heavy PAE during late pregnancy had significantly higher BMI z-scores (M = 0.75, SD = 0.69) and proportion overweight/obese (38.5%) than females not exposed to any prenatal alcohol (M = 0.29, SD = 1.07, P = 0.04; 23.8%, P = 0.03, respectively). There was no significant effect of heavy PAE on male adolescent BMI z-scores and proportion overweight/obese or adolescent waist-to-height ratios (all P > 0.05). CONCLUSIONS: Heavy PAE had a sex-specific effect on measures of adiposity in early adolescence, with girls more likely to have increased BMI and overweight/obesity status. Further longitudinal follow-up of children exposed to PAE is required to confirm if maternal alcohol consumption is a risk factor for later life obesity.

Significance of Neoadjuvant Downstaging in Carcinoma of Esophagus and Gastroesophageal Junction.

OBJECTIVE: To determine the impact of downstaging on outcomes in esophageal cancer, the prognostic value of clinical and pathological stage, and the difference in survival in patients with similar pathological stages with and without neoadjuvant treatment. BACKGROUND: There is little data evaluating adenocarcinoma and squamous cell carcinoma (SCC) and difference in outcomes for similar pathological stage with and without neoadjuvant treatment. PATIENTS AND METHODS: Consecutive patients with esophageal cancer from a single center were evaluated. Patients with esophageal adenocarcinoma or SCC treated with transthoracic esophagectomy and two-field lymphadenectomy were included. Comparison of outcomes with those primarily treated with surgery was made. The cTNM and ypTNM 8th edition was used. RESULTS: This study included 992 patients, of whom 417 received surgery alone and 575 received neoadjuvant therapy and surgery. In the neoadjuvant group, 7 (1%) had cTNM stage 2 and 418 (73%) had cTNM stage 3. Downstaging rates were similar between adenocarcinoma and SCC (54% vs. 61%, p = 0.5). Downstaging was associated with longer survival than patients with no change (adenocarcinoma, median: 82 vs. 26 months, p < 0.001; SCC, median: NR vs. 29 months, p < 0.001). On Cox regression analysis, downstaging was associated with significantly longer survival in adenocarcinoma but not in SCC. For SCC and more advanced adenocarcinoma, overall survival was significantly better when comparing like-for-like ypTN to pTN groups. CONCLUSIONS: Pathological stage provides a better estimate of prognosis compared with clinical stage. Downstaged patients may have an improved outcome over those with comparable pathological stage who did not receive neoadjuvant treatment.

Anastomotic Leak Does Not Impact on Long-Term Outcomes in Esophageal Cancer Patients.

BACKGROUND: Esophagectomy is a technically demanding procedure associated with high levels of morbidity. Anastomotic leak (AL) is a common complication with potentially major ramifications for patients. It has also been associated with poorer long-term overall survival (OS) and disease recurrence. OBJECTIVE: The aim of this study was to determine whether AL contributes to poor OS and recurrence-free survival (RFS) for patients with esophageal cancer. METHODS: Consecutive patients undergoing a two-stage, two-field transthoracic esophagectomy from a single high-volume unit between 1997 and 2016 were evaluated. Clinicopathologic characteristics, along with oncological and postoperative outcomes, were stratified by no AL versus non-severe leak (NSL) versus severe esophageal AL (SEAL). SEAL was defined as ALs associated with Clavien-Dindo grade III/IV complications. RESULTS: This study included 1063 patients, of whom 8% (87/1063) developed AL; 45% of those who developed AL were SEALs (39/87). SEAL was associated with a prolonged critical care stay (median 8 vs. 3 vs. 2 days; p < 0.001) and prolonged hospital stay (median 43 vs. 27 vs. 15 days; p < 0.001) compared with NSL or no AL. There were no significant differences in number of lymph nodes harvested and rates of R1 resection between groups. OS and RFS were not affected by either NSL or SEAL, and Cox multivariate regression showed NSL and SEAL were not independently associated with OS and RFS. Sensitivity analysis in patients receiving neoadjuvant therapy followed by esophagectomy demonstrated similar findings. CONCLUSION: These results demonstrate that AL leads to prolonged critical care and in-hospital length of stay; however, contrary to previous reports, our results do not compromise long-term outcomes and are unlikely to have a detrimental oncological impact.

Delivering esophago-gastric cancer care during the COVID-19 pandemic in the United Kingdom: a surgical perspective.

BACKGROUND: The COVID-19 pandemic continues to have a significant impact on the provision of medical care. Planning to ensure there is capability to treat those that become ill with the virus has led to an almost complete moratorium on elective work. This study evaluates the impact of COVID-19 on cancer, in particular surgical intervention, in patients with esophago-gastric cancer at a high-volume tertiary center. METHODS: All patients undergoing potential management for esophago-gastric cancer from 12 March to 22 May 2020 had their outcomes reviewed. Multi-disciplinary team (MDT) decisions, volume of cases, and outcomes following resection were evaluated. RESULTS: Overall 191 patients were discussed by the MDT, with a 12% fall from the same period in 2019, including a fall in new referrals from 120 to 83 (P = 0.0322). The majority of patients (80%) had no deviation from the pre-COVID-19 pathway. Sixteen patients had reduced staging investigations, 4 had potential changes to their treatment only, and 10 had a deviation from both investigation and potential treatment. Only one patient had palliation rather than potentially curative treatment. Overall 19 patients underwent surgical resection. Eight patients (41%) developed complications with two (11%) graded Clavien-Dindo 3 or greater. Two patients developed COVID-19 within a month of surgery, one spending 4 weeks in critical care due to respiratory complications; both recovered. Twelve patients underwent endoscopic resections with no complications. CONCLUSION: Care must be taken not to compromise cancer treatment and outcomes during the COVID-19 pandemic. Excellent results can be achieved through meticulous logistical planning, good communication, and maintaining high-level clinical care.

Long-term outcomes of clinical and pathological-staged T3 N3 esophageal cancer.

Locally advanced esophageal cancer is associated with poor long-term survival. Pre- and post-treatment stages may differ because of neoadjuvant therapy and inaccuracies in staging. The aim of this study was to determine the outcomes of patients staged with clinical T3 N3 and pathological T3 N3 carcinoma of the esophagus and determine differences between the groups. Consecutive patients from a single unit between 2010 and 2018 were included with either clinical (cT3 N3) or pathological (pT3 N3) esophageal cancer. Outcomes were compared between patients that underwent esophagectomy with or without neoadjuvant treatment and those patients staged cT3 N3 treated non-surgically (NSR). Patients were staged using the TNM 8. This study included 156 patients, 63 patients were staged cT3 N3 initially and had NSR treatment, only three of these had radical treatment. Of the remaining 93 patients who underwent esophagectomy, 34 were initially staged as cT3 N3, 54 were found to be pT3 N3 having been staged earlier initially, and five were unchanged before and after treatment. Median overall survival (OS) for surgical cT3 N3 patients was significantly longer than pT3 N3 and NSR (median: NR vs 19 vs 8 months, P < 0.001). Twenty-seven patients with cT3 N3 had lower staging following treatment, while three had a higher stage. T3 N3 disease carries a poor prognosis. Within this cohort, cT3 N3 disease treated surgically has a high 5-year OS suggesting possible over-staging and stage migration due to neoadjuvant therapy. Those not having surgery, have a dismal prognosis. The impact of neoadjuvant treatment cannot be predicted and, current staging modalities may be inaccurate. Clinical stage should be used with caution when counseling patients regarding management and prognosis.

[Hospital costs estimation by micro and gross-costing approaches]. / Estimation du coût hospitalier : approches par « micro-costing ¼ et « gross-costing ¼.

Cost analysis has become increasingly commonplace in healthcare facilities in recent years. Regardless of the aim, the first consideration for a hospital costing process is to determine the point of view, or perspective, to adopt. Should the cost figures reflect the healthcare facility's point of view or enlighten perspectives for the public health insurance system? Another consideration is in regard to the method to adopt, as there are several. The two most widely used methods to determine the costs of hospital treatments in France are the micro-costing method and the gross-costing method. The aims of this work are: (1) to describe each of these methods (e.g. data collection, assignment of monetary value to resource consumption) with their advantages and shortcomings as they relate to the difficulties encountered with their implementation in hospitals; (2) to present a review of the literature comparing the two methods and their possible combination; and (3) to propose ways to address the questions that need to be asked before compiling resource consumption data and assigning monetary value to hospital costs. A final diagram summarizes methodologies to be preferred according to the evaluation strategy and the impact on patient care.

Management and outcomes of anastomotic leaks after oesophagectomy.

BACKGROUND: Leaks following oesophagectomy include true anastomotic leaks, leaks from the gastrotomy and gastric conduit necrosis. Historically, these complications were associated with high mortality rates. Recent improvements in outcome have been attributed to the wider use of oesophageal stents in patient management. This study examined outcomes of patients who developed a leak in a single high-volume institution that did not use stenting as a primary treatment modality. METHODS: All patients undergoing an oesophagectomy between January 2009 and December 2013 were included. Patients were identified from a prospectively maintained database. RESULTS: A total of 390 oesophagectomies were performed (median age 65 (range 32-81) years). In 96·7 per cent of patients this was a two-stage subtotal oesophagectomy. Overall in-hospital and 90-day mortality rates were both 2·1 per cent (8 patients). Some 31 patients (7·9 per cent) developed a leak (median age 64·5 (range 52-80) years), of whom 27 (87 per cent) were initially managed without surgery, whereas four (13 per cent) required immediate thoracotomy. The median length of stay for patients with a leak was 41·5 (range 15-159) days; none of these patients died. CONCLUSION: Leaks can be managed with excellent outcomes without using oesophageal stents. The results do not support the widespread adoption of endoscopic stenting.

Knowledge, Skills and Experience Managing Tracheostomy Emergencies: A Survey of Critical Care Medicine trainees >.

Since the development of percutaneous tracheostomy, the number of tracheostomy patients on hospital wards has increased. Problems associated with adequate tracheostomy care on the wards are well documented, particularly the management of tracheostomy-related emergencies. A survey was conducted among non-consultant hospital doctors (NCHDs) starting their Critical Care Medicine training rotation in a university affiliated teaching hospital to determine their basic knowledge and skills in dealing with tracheostomy emergencies. Trainees who had received specific tracheostomy training or who had previous experience of dealing with tracheostomy emergencies were more confident in dealing with such emergencies compared to trainees without such training or experience. Only a minority of trainees were aware of local hospital guidelines regarding tracheostomy care. Our results highlight the importance of increased awareness of tracheostomy emergencies and the importance of specific training for Anaesthesia and Critical Care Medicine trainees.

Online patient literature related to oesophageal surgery: the need for greater readability, accreditation and higher quality.

INTRODUCTION: Oesophageal cancer is the sixth most common cause of death worldwide but is treatable through surgery. As part of the consenting process, surgeons may guide patients towards online information leaflets to understand more about their condition and treatment. This review aimed to systematically analyse some of the current resources that can be accessed via the internet. METHODS: A stringent search criteria was used to select online patient information leaflets for oesophageal cancer surgery. Leaflets were scored based on the Flesch-Kincaid Reading Ease score, DISCERN score, Health on the Net Code of Conduct (HONcode) certification/Information Standard Certification and International Patient Decision Aid Standards (IPDAS) score. FINDINGS: Only five sites had achieved HONcode certification. Only three sources were deemed readable using the Flesch-Kincaid scoring system and no sources reached the recommended readability using IPDAS. No source reached a maximum score with DISCERN, with the mean overall quality being 2.98. There was no significant difference between accredited and unaccredited sources. From our sample, patient information sources on oesophageal cancer surgery have a low readability. CONCLUSIONS: More research is required to ascertain patient behaviour with regards to accessing the literature. Patients and healthcare professionals should liaise with each other to produce more readable, high-quality patient information on oesophageal cancer surgery.

The impact of age on long-term survival following gastrectomy for gastric cancer.

INTRODUCTION: Gastrectomy remains the primary curative treatment modality for patients with gastric cancer. Concerns exist about offering surgery with a high associated morbidity and mortality to elderly patients. The study aimed to evaluate the long-term survival of patients with gastric cancer who underwent gastrectomy comparing patients aged <70 years with patients aged ≥70 years. METHODS: Consecutive patients who underwent gastrectomy for adenocarcinoma with curative intent between January 2000 and December 2017 at a single centre were included. Patients were stratified by age with a cut-off of 70 years used to create two cohorts. Log rank test was used to compare overall survival and Cox multivariable regression used to identify predictors of long-term survival. RESULTS: During the study period, 959 patients underwent gastrectomy, 520 of whom (54%) were aged ≥70 years. Those aged <70 years had significantly lower American Society of Anesthesiologists grades (p<0.001) and were more likely to receive neoadjuvant chemotherapy (39% vs 21%; p<0.001). Overall complication rate (p=0.001) and 30-day postoperative mortality (p=0.007) were lower in those aged <70 years. Long-term survival (median 54 vs 73 months; p<0.001) was also favourable in the younger cohort. Following adjustment for confounding variables, age ≥70 years remained a predictor of poorer long-term survival following gastrectomy (hazard ratio 1.35, 95% confidence interval 1.09, 1.67; p=0.006). CONCLUSIONS: Low postoperative mortality and good long-term survival were demonstrated for both age groups following gastrectomy. Age ≥70 years was, however, associated with poorer outcomes. This should be regarded as important factor when counselling patients regarding treatment options.

Randomized clinical trial of omega-3 fatty acid-supplemented enteral nutrition versus standard enteral nutrition in patients undergoing oesophagogastric cancer surgery.

BACKGROUND: Oesophagogastric cancer surgery is immunosuppressive. This may be modulated by omega-3 fatty acids (O-3FAs). The aim of this study was to assess the effect of perioperative O-3FAs on clinical outcome and immune function after oesophagogastric cancer surgery. METHODS: Patients undergoing subtotal oesophagectomy and total gastrectomy were recruited and allocated randomly to an O-3FA enteral immunoenhancing diet (IED) or standard enteral nutrition (SEN) for 7 days before and after surgery, or to postoperative supplementation alone (control group). Clinical outcome, fatty acid concentrations, and HLA-DR expression on monocytes and activated T lymphocytes were determined before and after operation. RESULTS: Of 221 patients recruited, 26 were excluded. Groups (IED, 66; SEN, 63; control, 66) were matched for age, malnutrition and co-morbidity. There were no differences in morbidity (P = 0·646), mortality (P = 1·000) or hospital stay (P = 0·701) between the groups. O-3FA concentrations were higher in the IED group after supplementation (P < 0·001). The ratio of omega-6 fatty acid to O-3FA was 1·9:1, 4·1:1 and 4·8:1 on the day before surgery in the IED, SEN and control groups (P < 0·001). There were no differences between the groups in HLA-DR expression in either monocytes (P = 0·538) or activated T lymphocytes (P = 0·204). CONCLUSION: Despite a significant increase in plasma concentrations of O-3FA, immunonutrition with O-3FA did not affect overall HLA-DR expression on leucocytes or clinical outcome following oesophagogastric cancer surgery. REGISTRATION NUMBER: ISRCTN43730758 (http://www.controlled-trials.com).

Caregiver-reported physical health status of children and young people with fetal alcohol spectrum disorder.

While fetal alcohol spectrum disorder (FASD) has primarily been thought of as a neurodevelopmental condition, research is beginning to highlight its 'whole-body' implications. Accordingly, the current study sought to provide a snapshot of potential health issues. Caregivers of children (median age of 12 years) with an FASD diagnosis were invited to participate in an online survey. Information relating to sample demographics, FASD status of the child and health outcomes were collected. The prevalence of health conditions reported in the FASD sample was compared against national prevalence data. Multiple linear regression utilising a stepwise approach was used to investigate potential predictors of the number of diagnosed health conditions. Survey data were from an international cohort (n = 197), with the majority of respondents based in Australia (40.2%) or the United States (27.7%). The most commonly reported diagnosed health conditions were eye conditions (44.7%), asthma (34.5%), heart conditions (34.0%) and skin conditions (27.4%). Binomial testing indicated the proportion of children diagnosed with these disorders was generally higher in the current FASD population, compared to national prevalence data. Indicators of metabolic dysfunction including diabetes and obesity were not significantly different compared to national prevalence data. Age of FASD diagnosis, existence of comorbid mental health conditions and the primary caregiver being in paid work were identified as being associated with the prevalence of diagnosed health conditions. Overall, the study has provided an up-to-date snapshot of health problems reported in a sample of children with FASD, confirming their increased risk of adverse health outcomes.

Alterations to Placental Glucocorticoid Receptor Expression with Alcohol Consumption.

Maternal alcohol consumption during pregnancy results in elevated vulnerability to intrauterine growth restriction, preterm birth, miscarriage, and stillbirth. Many of the detrimental effects of fetal alcohol exposure may be mediated through placental dysfunction; however, the exact mechanisms remain unknown. Here, we aimed to determine the effect of maternal alcohol exposure prior to and during early pregnancy on placental glucocorticoid receptor (GR) isoforms, associated GR regulated genes, and infant outcomes. Participants carrying singleton fetuses (n = 113) were recruited during early pregnancy. Amount and type of alcohol consumed over the last 12 months were obtained at 18 weeks of gestation. The level of drinking was separated into none (0 g/day), low (< 10 g/day), moderate (10-100 g/day), and heavy (> 100 g/day). At delivery, placental weight, infant sex, birthweight, and head circumference were recorded. Placental GR isoforms and genes involved in downstream signalling pathways were quantified. The majority of women (70.8%) consumed alcohol. Of these, most consumed low (48.8%) or moderate (37.5%) amounts. Placental weight was unaffected by alcohol consumption, but infants born to heavy drinkers tended to be lighter at birth. In female, but not male, placentae, maternal alcohol consumption resulted in increased GRαC and decreased GRαD1 cytoplasmic expression. In both female and male placentae, a dampened inflammatory response was evident with maternal alcohol consumption, involving downregulated IL6R and upregulated POU2F2 gene expression, respectively. Maternal alcohol consumption in the months prior to, and/or during early, pregnancy alters placental GR isoform and expression of some inflammatory genes in a sex-specific manner.

Protein disulfide isomerase does not control recombinant IgG4 productivity in mammalian cell lines.

Post-translational limitations in the endoplasmic reticulum during recombinant monoclonal antibody production are an important factor in lowering the capacity for synthesis and secretion of correctly folded proteins. Mammalian protein disulfide isomerase (PDI) has previously been shown to have a role in the formation of disulfide bonds in immunoglobulins. Several attempts have been made to improve the rate of recombinant protein production by overexpressing PDI but the results from these studies have been inconclusive. Here we examine the effect of (a) transiently silencing PDI mRNA and (b) increasing the intracellular levels of members of the PDI family (PDI, ERp72, and PDIp) on the mRNA levels, assembly and secretion of an IgG4 isotype. Although transiently silencing PDI in NS0/2N2 cells suggests that PDI is involved in disulfide bond formation of this subclass of antibody, our results show that PDI does not control the overall IgG4 productivity. Furthermore, overexpression of members of the PDI family in a Chinese hamster ovary (CHO) cell line does not improve productivity and hence we conclude that the catalysis of disulfide bond formation is not rate limiting for IgG4 production.

Parent-reported sleep problems in school-aged children with fetal alcohol spectrum disorder: association with child behaviour, caregiver, and family functioning.

OBJECTIVE/BACKGROUND: Sleep problems are a common clinically reported area of concern for children and adolescents with fetal alcohol spectrum disorder (FASD). However, limited empirical research has been undertaken investigating sleep problems for children with FASD. The current study aimed to examine the associations between parent-reported sleep problems in children with FASD and child behaviour, caregiver mental health and health-related quality of life and family functioning. PARTICIPANTS: 163 caregivers of children diagnosed with FASD aged 5-17 years were included in the current study. METHOD: Cross-sectional online survey that collected information pertaining to child sleep problems (difficulty falling asleep, difficulty staying asleep and/or frequent waking during the night and waking early in the morning) and standardised caregiver reported measures of child behaviour, caregiver mental wellbeing, caregiver health-related quality of life, and family functioning. RESULTS: Sleep problems were common, affecting 65.6% (n = 107) of participants. Difficulty falling asleep (56.4%) was the most common sleep problem encountered, followed by difficulty staying asleep (44.8%) and waking early (29.4%). Sleep problems were associated with increased rates of child behaviour problems and caregiver anxiety and negative impacts on caregiver and family quality of life. CONCLUSION: Sleep problems in children and adolescents with FASD are common and associated with poorer child, caregiver and family outcomes. Future research needs to determine whether effective identification and management of sleep problems can reduce adverse outcomes.

Trainee performance in radical gastrectomy and its effect on outcomes.

BACKGROUND: This study aimed to determine whether trainee involvement in D2 gastrectomies was associated with adverse outcomes. METHODS: Data from a prospectively created database of consecutive patients undergoing open D2 total (TG) or subtotal (STG) gastrectomy with curative intent between January 2009 and January 2014 were reviewed. Short- and long-term clinical outcomes were compared in patients operated on by consultants and those treated by trainees under consultant supervision. RESULTS: A total of 272 D2 open gastrectomies were performed, 123 (45·2 per cent) by trainees. There was no significant difference between consultants and trainees in median duration of surgery (TG: 240 (range 102-505) versus 240 (170-375) min respectively, P = 0·452; STG: 225 (150-580) versus 212 (125-380) min, P = 0·192), number of resected nodes (TG: 30 (13-101) versus 30 (11-102), P = 0·681; STG: 26 (5-103) versus 25 (1-63), P = 0·171), length of hospital stay (TG: 15 (7-78) versus 15 (8-65) days, P = 0·981; STG: 10 (6-197) versus 14 (7-85) days, P = 0·242), overall morbidity (TG: 44 versus 49 per cent, P = 0·314; STG: 34 versus 25 per cent, P = 0·113) or mortality (TG: 4 versus 2 per cent; P = 0·293). No difference in predicted 5-year overall survival was noted between the two cohorts (TG: 68 per cent for consultants versus 77 per cent for trainees, P = 0·254; STG: 70 versus 75 per cent respectively, P = 0·512). The trainee cohort had lower median blood loss for both TG (360 (range 90-1200) ml versus 600 (70-2350) ml for consultants; P = 0·042) and STG (235 (50-1000) versus 360 (50-3000) ml respectively; P = 0·053). CONCLUSION: Clinical outcomes were not compromised by supervised trainee involvement in D2 open gastrectomy.

ANTECEDENTES: El hecho de que en operaciones complejas la experiencia quirúrgica sea limitada puede influir en los resultados. Esto puede ser especialmente relevante cuando estas operaciones son realizadas por cirujanos en formación bajo supervisión. El objetivo de este estudio fue determinar si la participación del cirujano en formación en las gastrectomías D2 se asociaba con resultados adversos. MÉTODOS: Se revisó la información recogida en una base de datos prospectiva de pacientes consecutivos sometidos a gastrectomía D2 abierta total (total gastrectomy, TG) o subtotal (subtotal gastrectomy, STG) con intención curativa desde enero de 2009 a enero de 2014. Los pacientes se dividieron en dos grupos, uno de pacientes operados por un cirujano consultor y otro, de pacientes operados por un cirujano en periodo formación bajo la supervisión de un cirujano consultor. Se compararon los resultados clínicos a corto y largo plazo incluyendo la supervivencia global esperada a los cinco años. RESULTADOS: Se realizaron un total de 272 gastrectomías D2 abiertas (45% por cirujanos en periodo de formación). Las características demográficas de los pacientes fueron similares en los grupos de los cirujanos en formación y cirujanos consultores. En la TG y STG, no se apreciaron diferencias significativas entre ambas cohortes en el tiempo operatorio (P = 0,45)y (P = 0,19), número de ganglios linfáticos extirpados (P = 0,68) y (P = 0,17), duración de la estancia hospitalaria (P = 0,98) y (P = 0,24), morbilidad global (P = 0,31) y (P = 0,11), mortalidad (P = 0,29) y supervivencia global esperada a los 5 años (P = 0,25) y (P = 0,51). La pérdida sanguínea en ambas TG y STG fue menor en la cohorte de cirujanos en formación (P < 0,05). CONCLUSIÓN: La práctica de una gastrectomía D2 abierta por cirujanos en periodo de formación supervisados por consultores no comprometían los resultados clínicos.

Physiologically relevant screening of polyphenol-rich commercial preparations for bioactivity in vascular endothelial cells and application to healthy volunteers: A viable workflow and a cautionary tale.

This study describes the screening of 13 commercially-available plant extracts for pharmacological activity modulating vascular function using an endothelial cell model. A French maritime pine bark extract (FMPBE) was found to have the greatest effect upon nitric oxide availability in control (181% ± 36% of untreated cells) and dysfunctional cells (132% ± 8% of untreated control cells). In healthy volunteers, the FMPBE increased plasma nitrite concentrations 8 h post-consumption compared to baseline (baseline corrected median 1.71 ± 0.38 (25% IQR) and 4.76 (75% IQR) µM, p < 0.05). This was followed by a placebo-controlled, healthy volunteer study, which showed no effects on plasma nitrite. It was confirmed that different batches of extract had been used in the healthy volunteer studies, and this second batch lacked bioactivity, assessed using the in vitro model. No difference in plasma catechin levels was seen at 8 h following supplementation between the studies (252 ± 194 nM versus 50 ± 64 nM, p > 0.05), however HPLC-UV fingerprinting showed that the new batch had a 5-15% in major constituents (including procyanidins A2, B1 and B2) compared to the original batch. This research describes a robust mechanism for screening bioactive extracts for vascular effects. It also highlights batch variability as a significant limitation when using complex extracts for pharmacological activity, and suggests the use of in vitro systems as a tool to identify this problem in future studies.

Differential effect of hormones on macromolecular synthesis and mitosis in chick embryo cells.

Exposure of serum-deprived confluent monolayers of chick embryo cells to fresh serum results in maximal stimulation of synthesis of RNA and protein followed by increased DNA synthesis and mitosis. The addition of insulin to quiescent cultures effects a similar acceleration of synthesis of RNA and protein, but little stimulation of DNA synthesis and mitosis is evident. However, the simultaneous addition of insulin and hydrocortisone to resting cells causes a significant increase in the rate of DNA synthesis although the level reached is considerably lower than that obtained with serum and still no mitosis occurs. Unexpectedly, insulin plus hydrocortisone prevents maximal synthesis of RNA and protein in contrast to insulin-treated cultures. Nuclear autoradiography and percent mitosis of cells incubated with various regulatory factors indicate that cell heterogeneity exists and is reflected in the metabolic responses of subpopulations to specific regulatory signals.