Emerging Lipid Targets in Glioblastoma.

GBM accounts for most of the fatal brain cancer cases, making it one of the deadliest tumor types. GBM is characterized by severe progression and poor prognosis with a short survival upon conventional chemo- and radiotherapy. In order to improve therapeutic efficiency, considerable efforts have been made to target various features of GBM. One of the targetable features of GBM is the rewired lipid metabolism that contributes to the tumor's aggressive growth and penetration into the surrounding brain tissue. Lipid reprogramming allows GBM to acquire survival, proliferation, and invasion benefits as well as supportive modulation of the tumor microenvironment. Several attempts have been made to find novel therapeutic approaches by exploiting the lipid metabolic reprogramming in GBM. In recent studies, various components of de novo lipogenesis, fatty acid oxidation, lipid uptake, and prostaglandin synthesis have been considered promising targets in GBM. Emerging data also suggest a significant role hence therapeutic potential of the endocannabinoid metabolic pathway in GBM. Here we review the lipid-related GBM characteristics in detail and highlight specific targets with their potential therapeutic use in novel antitumor approaches.

The patient safety practices of emergency medical teams in disaster zones: a systematic analysis.

INTRODUCTION: Disaster zone medical relief has been criticised for poor quality care, lack of standardisation and accountability. Traditional patient safety practices of emergency medical teams (EMTs) in disaster zones were not well understood. Improving the quality of healthcare in disaster zones has gained importance within global health policy. Ascertaining patient safety practices of EMTs in disaster zones may identify areas of practice that can be improved. METHODS: A systematic search of OvidSP, Embase and Medline databases; key journals of interest; key grey literature texts; the databases of the WHO, Médecins Sans Frontieres and the International Committee of the Red Cross; and Google Scholar was performed. Descriptive studies, case reports, case series, prospective trials and opinion pieces were included with no limitation on date or language of publication. RESULTS: There were 9685 records, evenly distributed between the peer-reviewed and grey literature. Of these, 30 studies and 9 grey literature texts met the inclusion criteria and underwent qualitative synthesis. From these articles, 302 patient safety statements were extracted. Thematic analysis categorised these statements into 84 themes (total frequency 632). The most frequent themes were limb injury (9%), medical records (5.4%), surgery decision-making (4.6%), medicines safety (4.4%) and protocol (4.4%). CONCLUSION: Patient safety practices of EMTs in disaster zones are weighted toward acute clinical care, particularly surgery. The management of non-communicable disease is under-represented. There is widespread recognition of the need to improve medical record-keeping. High-quality data and institutional level patient safety practices are lacking. There is no consensus on disaster zone-specific performance indicators. These deficiencies represent opportunities to improve patient safety in disaster zones.

Perioperative Enteral Immunonutrition Modulates Systemic and Mucosal Immunity and the Inflammatory Response in Patients With Periampullary Cancer Scheduled for Pancreaticoduodenectomy: A Randomized Clinical Trial.

OBJECTIVES: Nutritional deficiencies and immune dysfunction in cancer patients may contribute to postoperative septic morbidity. This trial compared the effects of perioperative enteral immunonutrition (EIN) versus standard enteral nutrition (SEN) on systemic and mucosal immunity in patients undergoing pancreaticoduodenectomy for periampullary cancer. METHODS: Thirty-seven patients were randomized (EIN, n = 17; SEN, n = 20) to receive feed for 14 days preoperatively and 7 days postoperatively. Mediators of systemic immunity (interleukin 1α, tumor necrosis factor α, lymphocytes subsets, and complement components) and of mucosal immunity in duodenal biopsies, nutritional markers and parameters were evaluated. RESULTS: The groups were comparable for demographics, the concentrations of mediators of systemic and mucosal immunity at time of recruitment, and for the duration and amount of feed received. Preoperative EIN rather than SEN was associated with significant reductions in plasma tumor necrosis factor α and total hemolytic complement. Enteral immunonutrition-fed patients had significantly higher total lymphocyte count on the third postoperative day and significantly greater rise in CD4/CD8 ratio from day 3 to day 7 postoperatively compared with SEN-fed patients. CONCLUSIONS: The perioperative administration of EIN rather than SEN is associated with a favorable modulation of the inflammatory response and enhancement of systemic immunity in patients undergoing pancreaticoduodenectomy for periampullary cancer.

Multifocal necrotising fasciitis: an overlooked entity?

OBJECTIVE: The aim of the study is to report a case of multi-focal necrotising fasciitis, review research on this subject to identify common aetiological factors and highlight suggestions to improve management. CONTEXT: Necrotising fasciitis is a severe, life-threatening soft tissue infection that typically arises from a single area, usually secondary to a minor penetrating injury. Multi-focal necrotising fasciitis, where there is more than one non-contiguous area of necrosis, is much less commonly reported. There are no guidelines specific to the management of multi-focal necrotising fasciitis, and its under-reporting may lead to missed management opportunities. DESIGN: A systematic literature review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. DATA SOURCES: A search of MEDLINE, OLD MEDLINE and the Cochrane Collaboration was performed from 1966 to March 2011 using 16 search terms. DATA EXTRACTION: All articles were screened for genuine non-contiguous multi-focal necrotising fasciitis. Of the papers that met this criterion, data on patient demographics, likely inciting injury, presentation time-line, microbial agents, sites affected, objective assessment scores, treatment and outcome were extracted. DATA SYNTHESIS: A total of 31 studies met our inclusion criteria and 33 individual cases of multi-focal necrotising fasciitis were included in the quantitative analysis. About half (52%) of cases were type II necrotising fasciitis; 42% of cases had identifiable inciting injuries; 21% of cases developed multi-focal lesions non-synchronously, of which 86% were type II. Nearly all (94%) of cases had incomplete objective assessment scores. One case identified inflammatory imaging findings prior to clinical necrosis. CONCLUSIONS: Multifocality in necrotising fasciitis is likely to be associated with type II disease. We postulate that validated objective tools will aid necrotising fasciitis management pathways that will identify high-risk groups for multifocality and advise early pre-emptive imaging. We recommend the adoption of regional multi-focal necrotising fasciitis registers.

Predictors of remission of type 2 diabetes mellitus after laparoscopic gastric banding and bypass.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with obesity and results in considerable morbidity and mortality. Our objectives were to evaluate the effect of laparoscopic bariatric surgery on the control of T2DM in morbidly obese patients in a U.K. population and to determine the predictors of T2DM remission after bariatric surgery. The study was performed at teaching university hospitals and affiliated private hospitals. METHODS: Of 487 patients who underwent laparoscopic bariatric procedures from 2002 to 2007, 74 patients (15.2%) had established T2DM. The results are presented as the mean values. Multivariate analysis was used to identify the factors predictive of remission of T2DM after bariatric surgery. RESULTS: The body mass index before laparoscopic gastric bypass (LGB; n = 48) and laparoscopic adjustable gastric banding (LAGB; n = 26) were comparable (52 versus 51 kg/m(2), P = .508). At a mean follow-up of 16.9 months, 41% had remission and 59% had experienced improvement in T2DM. Although the duration of follow-up was significantly longer for the patients who had undergone LAGB than for those who had undergone LGB (23 versus 13.4 months, P = .001), the percentage of excess weight loss (%EWL) was significantly greater after LGB than after LAGB (59.4% versus 48.8%, P = .031), with an associated greater remission rate of T2DM (50% versus 24%, P = .034). Multivariate analysis revealed a greater %EWL and younger age to be independent predictors of postoperative remission of T2DM, and LGB, longer follow-up, and female gender were independent predictors of a greater %EWL. CONCLUSION: The %EWL was the only predictor of remission of T2DM that was influenced by the choice of bariatric procedure. In our study, LGB offered greater weight loss and a chance of remission of T2DM compared with LAGB and within 2 years of surgery.

Gut barrier dysfunction in critically ill surgical patients with abdominal compartment syndrome.

OBJECTIVES: This study investigated the effects of intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) on gut barrier function in critically ill surgical patients. METHODS: A prospective observational cohort study on patients with severe acute pancreatitis or abdominal sepsis admitted to an intensive care or high-dependency unit. Intra-abdominal pressure (IAP) and plasma levels of immunoglobulin G (IgG) and IgM antiendotoxin core antibodies (EndoCAb) and procalcitonin (ProCT) were measured serially. RESULTS: Among 32 recruited patients, 24 (75%) and 8 patients (25%) developed IAH and ACS, respectively. The state of ACS was associated with significant reductions in plasma IgG EndoCAb (P = 0.015) and IgM EndoCAb (P = 0.016) and higher concentrations of plasma ProCT (P = 0.056) compared with absence of ACS. Resolution of IAH and ACS was associated with significant recovery of plasma IgG EndoCAb (P = 0.003 and P = 0.009, respectively) and IgM EndoCAb (P = 0.002 and P = 0.003, respectively) and reduction in plasma ProCT concentration (P = 0.049 and P = 0.019, respectively). Negative correlations were observed between IAP and plasma IgG EndoCAb (P = 0.003) and IgM EndoCAb (P = 0.002). CONCLUSIONS: Intra-abdominal hypertension and ACS are associated with significantly higher endotoxin exposure and ProCT concentrations, suggestive of gut barrier dysfunction. Resolution of IAH and ACS is associated with evidence for recovery of gut barrier function.

Revision laparoscopic gastric bypass: an effective approach following failure of primary bariatric procedures.

BACKGROUND: The laparoscopic approach plays an important role in the primary surgical management of morbid obesity. This study evaluated the potential role of the laparoscopic approach to revision Roux-en-Y gastric bypass (LRYGB) in the management of selected patients who fail to lose adequate weight or regain weight after primary bariatric surgery. METHODS: Revision LRYGB was carried out to remedy early or delayed failure of primary bariatric procedures. Patients who underwent laparoscopic revision surgery to re-establish a functioning gastric band were not included in this report. The results are presented as mean (SD). RESULTS: Between April 2002 and March 2009, 21 patients underwent 21 laparoscopic revision procedures. The initial bariatric operations were laparoscopic gastric band (n = 10), open vertical banded gastroplasty (n = 6), open Magenstrasse and Mill (n = 2), open gastric bypass with pouch dilatation (n = 2), and open gastric band (n = 1). All revision procedures were completed laparoscopically and included conversion to LRYGB (n = 19), and others (n = 2). The postoperative hospital stay was 2.0 (1.3) days. The anastomotic leak, morbidity, and mortality rates were 0%, 4.8%, and 0% respectively. At a follow-up of 12.9 (7.9) months, the prerevision body mass index has decreased significantly from 43.9 (7.4) to 32.7 (6.6) kg/m(2) (p < 0.001) with a percentage excess weight loss of 61.1 (21.2). CONCLUSIONS: The laparoscopic approach to revision Roux-en-Y gastric bypass is safe and effective even in patients with previous open bariatric surgery and is associated with rapid recovery and short hospital stay.

Pseudoaneurysm of the anterior tibial artery after ankle arthroscopy.

Ankle arthroscopy is believed to have the least vascular complications compared with other types of arthroscopies. We present a case of traumatic pseudoaneurysm of the anterior tibial artery after ankle arthroscopy, an extremely rare complication that was treated surgically and had an uneventful recovery.