Evaluation of a laparoscopic liver resection in the setting of cirrhosis

Introduction: Patients presenting with cirrhosis and hepatic tumours represent a fragile group that have typically been avoided in early series of laparoscopic liver resection. This study was undertaken to evaluate the results of a laparoscopic hepatectomy in the setting of cirrhosis.Methods: Subgroup analysis of patients with cirrhosis within a series of 327 patients undergoing a laparoscopic resection was performed. Comparisons were made with patients without cirrhosis where appropriate to highlight differences in patient selection and outcomes. Specific variables assessed included operative details and short-term outcomes including length of stay (LOS), morbidity and mortality. Outcomes specific to hepatocellular carcinoma (HCC) were also assessed.Results: There were 52 patients with cirrhosis undergoing a laparoscopic hepatic resection. Ninety per cent of patients were Childs class A, with a median model for end-stage liver disease (MELD) score of 8. Hepatitis C was the most common cause of cirrhosis (88.5%), whereas the most common indication for an operation was HCC (71.2%). Resections were generally limited, with the median number of segments resected being 2 (range: 1–4). Complications occurred in 13 (25%) patients, with a 90-day mortality of 5.8%. The median LOS was 3 days.Conclusions: A laparoscopic hepatectomy is safe in the setting of cirrhosis, provided the application of appropriate selection criteria and sufficient experience with the procedure.     

Antibiotics and lactation: An overview of relative infant doses and a systematic assessment of clinical studies

Breastfeeding is important for the development of the child. Many antibiotics are considered safe during breastfeeding. The aim of the study was to assess the quality of lactation studies with antibiotics using the FDA and International Lactation Consultant Association quality guidelines for lactation studies. The secondary goal was to determine the exposure of the breastfed infant to antibiotics in relation to bacterial resistance and the developing microbiome. A literature search was performed and the included studies were scored on methodology, parameters concerning maternal exposure to antibiotics, maternal plasma and milk sampling. The infant exposure has been calculated and expressed as a percentage of a normal infant therapeutic dose. Sixty‐six studies were included in five antibiotic groups (broad‐spectrum penicillin, cephalosporins, macrolides and lincosamides, quinolones and sulphonamides). Cephalosporins were the most studied group of antibiotics (n = 21). Fifteen studies met all the criteria of “mother exposure to antibiotic”. Six studies met every criterion related to “plasma sampling”. Only one case report met all listed criteria for lactation studies. The correct calculation of infant exposure to antibiotics via the milk:plasma ratio (AUC) varies between 13% for macrolides and 38% for broad‐spectrum penicillin. The highest assessed exposure as a percentage of infant therapeutic dose was for metronidazole (11%). The studies meet to a limited extent with the quality standards for lactation research. The breastfed infants are exposed to a subtherapeutic concentration of antibiotics.     

Family history differs between young women with myocardial infarction and ischemic stroke: results from the RATIO case-control study

BackgroundFamily history may help in risk stratification, especially in the young. This study assesses the predictive value of a positive family history of cardiovascular disease for myocardial infarction (MI) and ischemic stroke (IS).Methods/ResultsThe RATIO study case–control study includes women with MI (N = 248), IS (N = 203) and 925 healthy matched controls. Odds ratios (ORs) and 95% confidence intervals (95%CI) were calculated with logistic regression. The risk of MI was almost fourfold increased in women with a family history positive for MI (OR 3.70, 95%CI 2.68–5.10), whereas the risk of IS was, if anything, only slightly elevated (1.25, 0.83–1.87). A family history of stroke (ischemic and hemorrhagic) was associated with a twofold increase in MI risk (2.00, 1.29–3.12), whereas the IS risk was again not clearly associated (1.37, 0.79–2.40).ConclusionsThe predictive value of a family history for cardiovascular disease differs between MI and IS.     

The urgency of the development of CO2 capture from ambient air

CO(2) capture and storage (CCS) has the potential to develop into an important tool to address climate change. Given society's present reliance on fossil fuels, widespread adoption of CCS appears indispensable for meeting stringent climate targets. We argue that for conventional CCS to become a successful climate mitigation technology-which by necessity has to operate on a large scale-it may need to be complemented with air capture, removing CO(2) directly from the atmosphere. Air capture of CO(2) could act as insurance against CO(2) leaking from storage and furthermore may provide an option for dealing with emissions from mobile dispersed sources such as automobiles and airplanes.     

Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML

Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.     

High VWF, low ADAMTS13, and oral contraceptives increase the risk of ischemic stroke and myocardial infarction in young women

VWF and ADAMTS13 are major determinants of platelet adhesion after vessel injury. In the present study, we aimed to determine whether VWF or ADAMTS13 plasma antigen levels influence the risks of ischemic stroke (IS) or myocardial infarction (MI) in young women and how these risks are affected by oral contraceptive (OC) use. VWF and ADAMTS13 plasma antigen levels were measured in a frequency-matched case-control study of 1018 young (18-49 years) women including 175 IS patients and 205 MI patients. Increasing levels of VWF and decreasing levels of ADAMTS13 were associated with the risk of IS and MI in a dose-dependent manner. Having both high VWF and low ADAMTS13 resulted in an odds ratio (OR) of 6.9 (95% confidence interval [95% CI], 2.0-23.0) for IS and 11.3 (95% CI, 3.6-35.2) for MI. Use of OCs increased the risk of IS and MI associated with high VWF (OR = 12; 95% CI, 5.5-26.2 and OR = 7.5, 95% CI, 3.6-15.7, respectively) and the risk of IS associated with low ADAMTS13 (OR = 5.8, 95% CI, 2.7-12.4). We conclude that high VWF and low ADAMTS13 plasma levels both increase the risk of IS and MI. The risks associated with high VWF or low ADAMTS13 levels are further increased by the use of OCs.     

Osteopontin is a prognostic factor for survival of acute myeloid leukemia patients

Osteopontin (OPN) is a glycoprotein that is secreted by osteoblasts and hematopoietic cells. OPN suppresses the proliferation of hematopoietic stem cells in vitro and may regulate the hematopoietic stem cell pool. Increased serum OPN concentrations occur in chronic myeloid leukemia, multiple myeloma, and acute myeloid leukemia (AML). In the present study, we analyzed the prognostic impact of OPN in AML by investigating the expression and relevance of OPN in newly diagnosed AML patients from 2 large study groups (the German AML Cooperative Group and the Dutch-Belgian Hematology Oncology Cooperative group). IHC (n = 84), ELISAs of blood/BM sera (n = 41), and microarray data for mRNA levels (n = 261) were performed. Expression of OPN protein was increased in AML patients both in BM blasts (IHC) and in BM serum (ELISA) compared with healthy controls. Patients expressing high levels of OPN within the BM (IHC) experienced shortened overall survival (OS; P = .025). Multivariate analysis identified karyotype, blast clearance (day 16), and the level of OPN expression as independent prognostic factors for OS. This prompted us to analyze microarray data from 261 patients from a third cohort. The analysis confirmed OPN as a prognostic marker. In summary, high OPN mRNA expression indicated decreased event-free survival (P = .0002) and OS (P = .001). The prognostic role of OPN was most prominent in intermediate-risk AML. These data provide evidence that OPN expression is an independent prognostic factor in AML.