Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis

INTRODUCTION: Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis. METHODS: This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls. RESULTS: Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-alpha/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-alpha and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45). CONCLUSIONS: The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis

Expedition 361 summary

International Ocean Discovery Program Expedition 361 drilled six sites on the southeast African margin (southwest Indian Ocean) and in the Indian-Atlantic Ocean gateway, from 30 January to 31 March 2016. In total, 5175 m of core was recovered, with an average recovery of 102%, during 29.7 days of on-site operations. The sites, situated in the Mozambique Channel at locations directly influenced by discharge from the Zambezi and Limpopo River catchments, the Natal Valley, the Agulhas Plateau, and Cape Basin, were targeted to reconstruct the history of the greater Agulhas Current system over the past ~5 My. The Agulhas Current is the strongest western boundary current in the Southern Hemisphere, transporting some 70 Sv of warm, saline surface water from the tropical Indian Ocean along the East African margin to the tip of Africa. Exchanges of heat and moisture with the atmosphere influence southern African climates, including individual weather systems such as extratropical cyclone formation in the region and rainfall patterns. Recent ocean model and paleoceanographic data further point at a potential role of the Agulhas Current in controlling the strength and mode of the Atlantic Meridional Overturning Circulation (AMOC) during the Late Pleistocene. Spillage of saline Agulhas water into the South Atlantic stimulates buoyancy anomalies that may influence basin-wide AMOC, with implications for convective activity in the North Atlantic and global climate change. The main objectives of the expedition were to establish the role of the Agulhas Current in climatic changes during the Pliocene–Pleistocene, specifically to document the dynamics of the Indian-Atlantic Ocean gateway circulation during this time, to examine the connection of the Agulhas leakage and AMOC, and to address the influence of the Agulhas Current on African terrestrial climates and coincidences with human evolution. Additionally, the expedition set out to fulfill the needs of Ancillary Project Letter number 845, consisting of high-resolution interstitial water sampling to help constrain the temperature and salinity profiles of the ocean during the Last Glacial Maximum. The expedition made major strides toward fulfilling each of these objectives. The recovered sequences allowed generation of complete spliced stratigraphic sections that range from 0 to between ~0.13 and 7 Ma. This sediment will provide decadal- to millennial-scale climatic records that will allow answering the paleoceanographic and paleoclimatic questions set out in the drilling proposal

Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

Utilising caging techniques to investigate metal assimilation in Nucella lapillus, Mytilus edulis and Crassostrea gigas at three Irish coastal locations

Peer-reviewed.Pollution by metals has been of increasing concern for a number of decades but at present, the mechanism of metal accumulation in sentinel species is not fully understood and further studies are required for environmental risk assessment of metals in aquatic environments. The use of caging techniques has proven to be useful for assessment of water quality in coastal and estuarine environments. This study investigates the application of caging techniques for monitoring uptake of 20 elements [Li, Na, Mg, Al, P, K, Ca, V, Cr, Mn, Fe, Ni, Co, Cu, As, Sb, Pb, Hg, Cd and Zn] in three marine species namely Nucella lapillus, Mytilus edulis and Crassostrea gigas. Stable isotopes were used to determine predatory effects and also used for modelling metal uptake in test species and to track nutrient assimilation. Metal levels were monitored at three different coastal locations, namely Dublin Bay, Dunmore East and Omey Island over 18 weeks. Significant differences in concentrations of Mn, Co and Zn between mussels and oysters were found. Correlations between cadmium levels in N. lapillus and δ13C and δ15N suggest dietary influences in Cd uptake. Levels of Zn were highest in C. gigas compared to the other two species and levels of Zn were most elevated at the Dunmore East site. Copper levels were more elevated in all test species at both Dublin Bay and Dunmore East. Mercury was raised in all species at Dunmore East compared to the other two sites. Biotic accumulation of metals in the test species demonstrates that caging techniques can provide a valid tool for biomonitoring in metal impacted areas.Technology Sector Research: Strand III: Core Research Strengths and from Dublin Institute of Technology’s Capacity Building Scheme (CaBS) for Strategic Research