Rationale and design of a proof-of-concept trial investigating the effect of uninterrupted perioperative (par)enteral nutrition on amino acid profile,cardiomyocytes structure,and cardiac perfusion and metabolism of patients undergoing coronary artery bypass grafting

Background  

Malnutrition is very common in patients undergoing cardiac surgery. Malnutrition can change myocardial substrate utilization which can induce adverse effects on myocardial metabolism and function. We aim to investigate the hypothesis that there is a disturbed amino acids profile in the cardiac surgical patient which can be normalized by (par)enteral nutrition before, during and after surgery, subsequently improving cardiomyocyte structure, cardiac perfusion and glucose metabolism.     

A randomized trial to assess the biological activity of short-term (pre-surgical) fulvestrant 500 mg plus anastrozole versus fulvestrant 500 mg alone or anastrozole alone on primary breast cancer

Introduction

Fulvestrant shows dose-dependent biological activity. Greater estrogen-receptor (ER) blockade may feasibly be achieved by combining fulvestrant with anastrozole. This pre-surgical study compared fulvestrant plus anastrozole versus either agent alone in patients with ER-positive breast cancer.

Methods

In this double-blind, multicenter trial, 121 patients received fulvestrant 500 mg on Day 1 plus anastrozole 1 mg/day for 14 to 21 days (F + A); fulvestrant plus anastrozole placebo (F); or fulvestrant placebo plus anastrozole (A), 2 to 3 weeks before surgery. ER, progesterone-receptor (PgR) and Ki67 expression were determined from tumor biopsies before treatment and at surgery.

Results

A total of 103 paired samples were available (F, n = 35; F+A, n = 31; A, n = 37). All treatments significantly reduced mean ER expression from baseline (F: -41%, P = 0.0001; F + A: -39%, P = 0.0001; A: -13%, P = 0.0034). F and F + A led to greater reductions in ER versus A (both P = 0.0001); F + A did not lead to additional reductions versus F. PgR and Ki67 expression were significantly reduced with all treatments (means were -34% to -45%, and -75% to -85%, respectively; all P = 0.0001), with no differences between groups.

Conclusions

In this short-term study, all treatments reduced ER expression, although F and F + A showed greater reductions than A. No significant differences were detected between the treatment groups in terms of PgR and Ki67 expression. No additional reduction in tumor biomarkers with combination treatment was observed, suggesting that F + A is unlikely to have further clinical benefit over F alone.

Trial registration

Clinicaltrials.gov NCT00259090.     

Surgery in (pre)malignant celiac disease

AIM: To report the outcome of surgery in patients with (pre)malignant conditions of celiac disease (CD) and the impact on survival.METHODS: A total of 40 patients with (pre)malignant conditions of CD, ulcerative jejunitis (n = 5) and enteropathy associated T-cell lymphoma (EATL) (n = 35), who underwent surgery between 2002 and 2013 were retrospectively evaluated. Data on indications, operative procedure, post-operative morbidity and mortality, adjuvant therapy and overall survival (OS) were collected. Eleven patients with EATL who underwent chemotherapy without resection were included as a control group for survival analysis. Patients were followed-up every three months during the first year and at 6-mo intervals thereafter.RESULTS: Mean age at resection was 62 years. The majority of patients (63%) underwent elective laparotomy. Functional stenosis (n = 13) and perforation (n = 12) were the major indications for surgery. In 70% of patients radical resection was performed. Early postoperative complications, mainly due to leakage or sepsis, occurred in 14/40 (35%) of patients. Eight patients required reoperation. More patients who underwent resection in the acute setting (n = 3, 20%) died compared to patients treated in the elective setting. With a median follow-up of 20 mo, seven patients (18%) required reoperation due to long-term complications. Significantly more patients who underwent acute surgery could not be treated with adjuvant chemotherapy. Patients who first underwent surgical resection showed significantly better OS than patients who received chemotherapy without resection.CONCLUSION: Although the complication rate is high, the preferred first step of treatment in (pre)malignant CD consists of local resection as early as possible to improve survival.     

Cardio-pulmonary resuscitation training, knowledge and attitudes of newly-qualified doctors in New Zealand in 2003

OBJECTIVE: To assess the resuscitation knowledge and confidence of newly-qualified doctors in New Zealand (NZ) in 2003. DESIGN: Anonymous questionnaires were distributed to all newly-qualified doctors in NZ (n=279). PARTICIPANTS: Two hundred and thirty-three respondents from hospitals throughout NZ (84% response rate). MAIN OUTCOME MEASURES: Resuscitation training received during medical school and use of recommended text (Level 7 of NZ resuscitation manual), confidence in resuscitation skills and core knowledge of basic and advanced resuscitation. RESULTS: 98.3% of doctors received advanced resuscitation training during their final year of medical school, of these 64.6% had received training in the previous 6 months. The mean knowledge score was 56.6% and 45% of doctors made 'fatal errors'. Eighty-four percentage of doctors had read the Level 7 manual and 72.6% found it very or extremely useful. Those who had read the manual had higher scores and were less likely to make a 'fatal error'. Having attended a cardiac arrest and having received training within the last 6 months improved doctor confidence in resuscitation. CONCLUSIONS: The resuscitation knowledge and confidence of newly-qualified doctors in NZ are sub-optimal, with some doctors displaying dangerous deficiencies. Our results suggest mandatory attainment of an advanced resuscitation certificate, six-monthly practical resuscitation sessions and increased exposure to real resuscitation situations should be implemented to improve undergraduate resuscitation training.     

Association between antidepressant drug use during pregnancy and child healthcare utilisation

Objective  To evaluate healthcare utilisation by children who were exposed to antidepressant drug use during pregnancy and those whose mothers stopped using antidepressants before pregnancy compared with a control group.
Design  Cohort study.
Setting  Health insurance records in the Netherlands.
Population  A total of 38 602 children born between 2000 and 2005.
Methods  Survey of child healthcare utilisation in relation to gestational antidepressant use.
Main outcome measure  Healthcare utilisation rates during the first year of life, with special emphasis to medical care related to cardiac disease.
Results  Children of mothers who used antidepressants during pregnancy showed increased healthcare use during the first year of life, independent of the mother's healthcare use. The relative risk of more than two visits to general practitioners was 1.5 (95% confidence interval, CI: 1.3–1.8) in the continuous antidepressant users group and 1.3 (95% CI: 1.2–1.5) in the group of children whose mothers stopped taking medication. In both study groups there was a trend towards more drug use for infections and inflammation compared with the control group. Children continuously exposed to antidepressants had an increased risk of cardiac interventions such as cardiovascular surgery or heart catheterisation, relative risk of 5.6 (95% CI: 1.8–17.4). The risk of physiotherapy was twice as high in the antidepressant group compared with the control group (relative risk 2.0; 95% CI: 1.5–2.6).
Conclusion  Antidepressant use during pregnancy is associated with increased child healthcare utilisation and increased risk of major cardiac interventions in early childhood.     

Paradigm shift in gastrointestinal surgery − combating sarcopenia with prehabilitation: Multimodal review of clinical and scientific data

A growing body of evidence has demonstrated the prognostic significance of sarcopenia in surgical patients as an independent predictor of postoperative complications and outcomes. These included an increased risk of total complications, major complications, re-admissions, infections, severe infections, 30 d mortality, longer hospital stay and increased hospitalization expenditures. A program to enhance recovery after surgery was meant to address these complications; however, compliance to the program since its introduction has been less than ideal. Over the last decade, the concept of prehabilitation, or “pre-surgery rehabilitation”, has been discussed. The presurgical period represents a window of opportunity to boost and optimize the health of an individual, providing a compensatory “buffer” for the imminent reduction in physiological reserve post-surgery. Initial results have been promising. We review the literature to critically review the utility of prehabilitation, not just in the clinical realm, but also in the scientific realm, with a resource management point-of-view.