Comparative transcriptome analysis of matched primary and distant metastatic ovarian carcinoma.

BACKGROUND: High grade serous ovarian carcinoma (HGSOC) is the most common subtype of epithelial ovarian cancers (EOC) with poor prognosis. In most cases EOC is widely disseminated at the time of diagnosis. Despite the optimal cytoreductive surgery and chemotherapy most patients develop chemoresistance, and the 5-year overall survival being only 25-35%. METHODS: Here we analyzed the gene expression profiles of 10 primary HGSOC tumors and 10 related omental metastases using RNA sequencing and identified 100 differentially expressed genes. RESULTS: The differentially expressed genes were associated with decreased embryogenesis and vasculogenesis and increased cellular proliferation and organismal death. Top upstream regulators responsible for this gene signature were NR5A1, GATA4, FOXL2, TP53 and BMP7. A subset of these genes were highly expressed in the ovarian cancer among the cancer transcriptomes of The Cancer Genome Atlas. Importantly, the metastatic gene signature was suggestive of poor survival in TCGA data based on gene enrichment analysis. CONCLUSION: By comparing the gene expression profiles of primary HGSOC tumors and their matched metastasis, we provide evidence that a signature of 100 genes is able to separate these two sample types and potentially predict patient survival. Our study identifies functional categories of genes and transcription factors that could play important roles in promoting metastases and serve as markers for cancer prognosis.

Propofol causes more hypotension than etomidate in patients with severe aortic stenosis: a double-blind, randomized study comparing propofol and etomidate.

BACKGROUND: Vasodilatation and hypotension are thought to be harmful in patients with severe aortic stenosis. Etomidate is preferred to propofol for anaesthesia induction in haemodynamically unstable patients, but may disturb cortisol synthesis. We assessed the haemodynamic effects of etomidate vs. propofol as anaesthesia induction agents, and the effects of these drugs on cortisol concentrations, in patients with severe aortic stenosis. The main end-point of the study was the incidence of hypotension. METHODS: Sixty-six patients with severe aortic stenosis scheduled for elective aortic valve replacement were enrolled in the study. The patients were randomized to receive either propofol or etomidate for induction of anaesthesia. Haemodynamic parameters, i.e. mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP) and cardiac index (CI), were measured. If MAP decreased below 70 mmHg for more than 30 s, phenylephedrine was administered. Serum cortisol concentrations were also measured. RESULTS: MAP decreased in all patients (P < 0.001). MAP decreased to a greater extent in patients receiving propofol than in those receiving etomidate (P = 0.006). Patients receiving propofol needed phenylephedrine more often than those receiving etomidate (20/30 vs. 8/30, P = 0.002). CI and PCWP decreased in both groups (P < 0.001), with no difference between the groups. Patients receiving etomidate had a lower serum cortisol concentration immediately after the operation than those receiving propofol (P < 0.001), but no differences between the groups were observed on the first post-operative morning. CONCLUSION: Propofol is twice as likely as etomidate to evoke hypotension in anaesthesia induction of patients with severe aortic stenosis; however, etomidate transiently decreases post-operative serum cortisol concentrations.

A prospective, randomized study of goal-oriented hemodynamic therapy in cardiac surgical patients.

UNLABELLED: Organ dysfunction and multiple organ failure are the main causes of prolonged hospital stay after cardiac surgery, which increases resource use and health care costs. Increased levels of oxygen delivery and consumption are associated with improved outcome in different groups of postoperative patients. Cardiac surgical patients are at risk of inadequate perioperative oxygen delivery caused by extracorporeal circulation and limited cardiovascular reserves. The purpose of our study was to test whether increasing oxygen delivery immediately after cardiac surgery would shorten hospital and intensive care unit (ICU) stay. Four hundred three elective cardiac surgical patients were enrolled in the study and randomly assigned to either the control or the protocol group. Goals of the protocol group were to maintain SvO(2) >70% and lactate concentration < or =2.0 mmol/L from admission to the ICU and up to 8 h thereafter. Hemodynamics, oxygen transport data, and organ dysfunctions were recorded. The median hospital stay was shorter in the protocol group (6 vs 7 days, P < 0.05), and patients were discharged faster from the hospital than those in the control group (P < 0.05). Discharge from the ICU was similar between groups (P = 0. 8). Morbidity was less frequent at the time of hospital discharge in the protocol group (1.1% vs 6.1%, P < 0.01). Increasing oxygen delivery to achieve normal SvO(2) values and lactate concentration during the immediate postoperative period after cardiac surgery can shorten the length of hospital stay. IMPLICATIONS: Health care economics has challenged clinicians to reduce costs and improve resource use in cardiac surgery and anesthesia in a patient population increasing in age and in severity of disease. Optimizing cardiovascular function to maintain adequate oxygen delivery during the immediate postoperative period after cardiac surgery can decrease morbidity and reduce length of hospital stay.

Relationship between intra- and postoperative oxygen transport and prolonged intensive care after cardiac surgery: a prospective study.

BACKGROUND: Prolonged intensive care is a rare but serious complication of cardiac surgery. It is required in less than 10% of operated patients but they use more than 30% of all the intensive care resources needed for cardiac surgery. The aim of our study was to describe the clinical course of the patients who need prolonged intensive care following cardiac surgery and to assess whether the intra- and postoperative oxygen transport variables are different in these patients as compared to patients with an uncomplicated course. METHODS: The study patients were divided into two groups according to the length of stay in the intensive care unit (ICU) after the operation: Group I, n = 241, ICU-stay < 5 days and Group II, n 20, ICU-stay > or = 5 days. Hemodynamic and oxygen transport data were prospectively obtained intra- and postoperatively and postoperative organ dysfunctions were recorded. RESULTS: The patients in the prolonged intensive care group tended to be older, have lower ejection fraction and longer cardiopulmonary bypass time. Postoperatively, this group had significantly increased oxygen extraction rate (P = 0.035, repeated measures for ANOVA). In the logistic regression analysis, increased oxygen extraction (31% in Group I vs. 36% in Group II, P < 0.005) at 6 hours after arrival at the intensive care unit had the strongest independent association with the need for prolonged intensive care. CONCLUSIONS: There was no significant relationship between the factors conventionally assumed to be risk factors for prolonged intensive care. Instead, an increase in whole body oxygen extraction, reflecting a mismatch between the whole body oxygen demand and supply, was associated with the need for prolonged intensive care. Oxygen extraction increased to compensate for the reduced oxygen delivery, which in turn was caused by a lower arterial oxygen content.

Effect of digital edge-enhancement on the visibility of normal parenchymal lung markings.

Digital 'conventional-like' (C-L) and edge-enhanced (E-E) posteroanterior chest roentgenograms of 42 healthy individuals were ranked twice (interval of at least 5 days) in the order of increasing lung parenchymal markings (a total of four rankings). This was done by three radiologists, two residents, one medical student and one radiographer. There was a good general consistency of rankings for both the C-L and E-E images. The correlation coefficients were best (median 0.600) (P < 0.05) between the consequent rankings of C-L images compared to the subsequent rankings of E-E images (median 0.440) and to the various combinations between the rankings of both kinds of images. Subtle differences in normal lung parenchyma could, therefore, generally (five of the seven observers) best be demonstrated in C-L images, but two observers managed best with the E-E images.

Observed lung markings in normal chest roentgenograms.

The digital chest posterior-anterior roentgenograms of 42 healthy individuals were ranked twice (interval of at least 5 days) in the order of increasing lung parenchymal markings. The evaluations were made by three radiologists, two residents, a medical student and a radiographer. All observers regardless of their radiological experience showed good intraobserver correlations between their two subsequent rankings (p < 0.05-0.001). The interobserver agreement on rankings was generally poor, even if the radiologists were considered. Radiologic training seemed to eliminate the influence of false leading factors (the object's respiration and body constitution). "The golden standard of evaluation" (= the added-up rankings by the radiologists) did not correlate either with the patient's ages (19-54 years) or smoking habits (0-45 pack-years, mean 4.2).