Sex differences in patients with gastrointestinal stromal tumours: do they exist and does it affect survival?

BACKGROUND: Sex differences in cancer have gained attention in recent years. The role of sex as a prognostic factor in gastrointestinal stromal tumours (GIST) has not been well established. The aim of this research was to elucidate potential sex differences in GIST patients and the influence of sex on disease-specific survival (DSS). METHODS: A review of the literature was carried out to obtain an overview of all literature with sex as a covariate on GIST survival analyses. Furthermore, in the Dutch GIST Registry, GIST characteristics between males and females were compared and the influence of sex on DSS was analysed. RESULTS: A total of 118 articles from the review of the literature met our selection criteria; 58% of the articles found no sex difference in survival and 42% did find a sex difference. All differences favoured female patients, although there was substantial overlap of individual patients in the various reported groups. The Dutch GIST Registry cohort consisted of 1425 patients (46% female). Compared with female patients, male patients had larger tumours (mean 9.0 cm versus 7.9 cm) and higher mitotic rates (34.4% versus 28.0% >5 mitoses/5 mm2). GIST in males was more often metastasized at diagnosis (21.3% versus 13.7%) and incurable (38.5% versus 31.0%). Male patients less often received surgery of the primary tumour (71.7% versus 78.9%), but did experience more tumour ruptures (18.2% versus 13.3%). Male patients had a worse DSS than females. This was not statistically significant when corrected for differences in GIST characteristics. CONCLUSIONS: In case of sex differences in GIST in the literature, male patients have a worse outcome. In our Dutch GIST cohort a similar finding was made, but sex was shown not to be an independent factor. Male patients more often had aggressive GISTs, with larger tumours, higher mitotic rates, more tumour ruptures, and metastases, which could explain the sex differences in DSS.

Priorities and preferences of advanced soft tissue sarcoma patients starting palliative chemotherapy: baseline results from the HOLISTIC study.

INTRODUCTION: Palliative chemotherapy is the principal treatment of patients with advanced soft tissue sarcomas (STS); however prognosis is limited (median overall survival 12-19 months). In this setting, patient values and priorities are central to personalised treatment decisions. PATIENTS AND METHODS: The prospective HOLISTIC study was conducted in the UK and the Netherlands assessing health-related quality of life in STS patients receiving palliative chemotherapy. Participants completed a questionnaire before starting chemotherapy, including attitudes towards quality of life (QoL) versus length of life (LoL), decisional control preferences, and decisional conflict. Chi-square and Fisher's exact tests were used to evaluate associations between patient characteristics and preferences. RESULTS: One hundred and thirty-seven patients with advanced STS participated (UK: n = 72, the Netherlands: n = 65). Median age was 62 (27-79) years. Preference for extended LoL (n = 66, 48%) was slightly more common than preference for QoL (n = 56, 41%); 12 patients (9%) valued LoL and QoL equally (missing: n = 3). Younger patients (age <40 years) prioritised LoL, whereas two-thirds of older patients (aged ≥65 years) felt that QoL was equally or more important than LoL (P = 0.020). Decisional conflict was most common in patients who prioritised QoL (P = 0.024). Most patients preferred an active (n = 45, 33%) or collaborative (n = 59, 44%) role in treatment decisions. Gender, performance status, and country were significantly associated with preferred role. Concordance between preferred and actual role in chemotherapy decision was high (n = 104, 76%). CONCLUSIONS: Heterogeneous priorities and preferences among advanced STS patients support personalised decisions about palliative treatment. Considering individual differences during treatment discussions may enhance communication and optimise patient-centred care.

Mercury in sediment cores from the southern Gulf of Mexico: Preindustrial levels and temporal enrichment trends.

Spatial and temporal variability of mercury concentrations in sediments was evaluated in 210Pb-dated sediment cores from offshore and intertidal areas in the southern Gulf of Mexico. In offshore cores, mercury concentrations were comparable (11.2-69.2 ng g-1), and intermediate between concentrations in intertidal cores from the eastern (6.0-34.4 ng g-1) and the western (34.9-137.7 ng g-1) inlets of Términos Lagoon. The enrichment factor (EF) indicated minimal contamination (EF < 2) in most offshore cores, whereas in some intertidal cores steadily increasing mercury enrichment and fluxes were observed along the past century. No evidence of oil industry related mercury contamination was found, as the minor but increasing enrichment in intertidal cores is most likely related to land-derived sources such as catchment eroded soils and waste water runoff. Results highlight the importance to control catchment erosion and untreated sewage releases to reduce mercury loadings to the coastal zone.

Natural and anthropogenic oil impacts on benthic foraminifera in the southern Gulf of Mexico.

The Campeche Sound is the major offshore oil producing area in the Southern Gulf of Mexico (SGoM). To evaluate the impact of oil related activities in the ocean floor sediments, we analyzed the geochemical (major and trace element, organic carbon and hydrocarbon concentrations) and biological (benthic foraminifera) composition of 62 superficial sediment samples, from 13 to 1336 m water depth. Cluster and Factor analysis of all the variables indicate that their distribution patterns are mainly controlled by differences between the terrigenous and carbonate platforms in the SGoM. Benthic foraminiferal assemblages were abundant and diverse, and their distribution patterns are mainly determined by water depth and sedimentary environment. However, most of the abundant species are opportunistic and/or low-oxygen tolerant, and many of their tests show oil stains and infillings, characteristic of oil polluted locations, suggesting the environment has been modified by natural seepage or oil-related activities. To determine if these conditions are natural or anthropogenic in origin, pre - industrial settings should be studied. Organic carbon (Corg) content (0.6-2.9%) and total hydrocarbon concentrations (PAHs 1.0-29.5 µg kg-1) were usually higher around the oil platforms area, the natural hydrocarbon seeps ("chapopoteras") area and offshore rivers, but there is no accumulation of oil related trace elements in these areas. However, the comparison with international sediment quality benchmarks indicates that Cd, Cr and Ni concentrations are above the threshold effect level, and also As, Ba and Cu are above the probable effect level benchmarks, which indicate that these element concentrations might be of potential ecological concern. Comprehensive studies involving different proxies, and assessing pre-industrial conditions, must be undertaken before assessing environmental health of marine benthic ecosystems.

Predictive factors for toxicity and survival of second-line sunitinib in advanced gastrointestinal stromal tumours (GIST).

Introduction: Sunitinib is a standard second-line treatment in advanced gastrointestinal stromal tumours (GIST). We aimed to search for predictive factors for grade 3 and 4 toxicity, progression-free survival (PFS) and overall survival (OS) in a GIST reference center patient population, outside clinical trials.Methods: A retrospective analysis was performed of patients treated in two European Comprehensive Cancer Centers between January 2005 and December 2015. Demographic and clinical features, tumour characteristics and biological parameters were investigated. Logistic regression models were used to find factors associated with grade 3 and 4 toxicity. To identify predictive factors for PFS and OS, variables that were statistically significant in univariate analysis were used in the multivariate Cox proportional hazards model.Results: Ninety-one patients were included in this analysis. Age >60 years (HR 5.0, p = .006) and body weight ≤70 kg (HR 4.7, p = .009) were predictive factors for grade 3 and 4 toxicity. When divided into two categories, non-haematological grade 3 and 4 toxicity was predicted by age >60 years (HR 3.8, p = .012) and body weight ≤70 kg (HR 3.3, p = .025) whereas haematological toxicity had no significantly associated predictive factors. The median PFS and OS with sunitinib were 8.8 months and 27.5 months, respectively. The use of imatinib less than six months compared to 6-12 months (HR 0.2, p = .013) and to >12 months (HR 0.3, p = .016) and liver and/or peritoneal metastases (HR 0.1, p < .001, HR 0.2, p = .003 and HR 0.2, p = .004) compared to locally advanced disease only were predictive for longer PFS. High neutrophil (HR 3.1, p = 0.04) and platelet count (HR 2.4, p = .046) predicted a shorter OS. Flexible sunitinib dosing was associated with superior OS (p = .021).Conclusion: In advanced GIST patients treated with sunitinib, older and low-weight patients are at risk for grade 3 and 4 toxicity. Clinical (prior imatinib use and metastases), biological (neutrophil and platelet count) and treatment characteristics independently predict PFS and OS.

Constraining the Spatial Extent of Marine Oil Snow Sedimentation and Flocculent Accumulation Following the Deepwater Horizon Event Using an Excess 210Pb Flux Approach.

Following the Deepwater Horizon (DWH) event in 2010, there were several lines of evidence indicating the presence of marine oil snow sedimentation and flocculent accumulation (MOSSFA). A significant amount of marine oil snow formed in the water column of the northern Gulf of Mexico (nGoM), settled rapidly, and ultimately accumulated in the sediments of the nGoM. This study utilized a commonly used radioisotope tracer (excess 210Pb, 210Pbxs) from 32 sediment cores collected from 2010 to 2013 to characterize the spatial extent of MOSSFA on the seafloor. Relative to pre-DWH conditions, an increase in 210Pbxs flux occurred in two distinct regions: (1) in the western portion of the study area on an east-northeast to west-southwest axis, stretching 230 km southwest and 140 km northeast of the DWH wellhead, and (2) in the eastern portion of the study area on a 70 km northeast to southwest axis near the DeSoto Canyon. The total sedimentary spatial extent of MOSSFA, as calculated by increased 210Pbxs flux after 2010, ranged from 12 805 to 35 425 km2. 210Pbxs flux provides a valuable tool for documenting the spatial extent of MOSSFA following DWH and will continue to aid in the determination of advective transport and ultimate depocenters of MOSSFA material.

Characterizing the variability of benthic foraminifera in the northeastern Gulf of Mexico following the Deepwater Horizon event (2010-2012).

Following the Deepwater Horizon (DWH) event in 2010 subsurface hydrocarbon intrusions (1000-1300 m) and an order of magnitude increase in flocculent hydrocarbon deposition caused increased concentrations of hydrocarbons in continental slope sediments. This study sought to characterize the variability [density, Fisher's alpha (S), equitability (E), Shannon (H)] of benthic foraminifera following the DWH event. A series of sediment cores were collected at two sites in the northeastern Gulf of Mexico from 2010 to 2012. At each site, three cores were utilized for benthic faunal analysis, organic geochemistry, and redox metal chemistry, respectively. The surface intervals (∼0-10 mm) of the sedimentary records collected in December 2010 at DSH08 and February 2011 at PCB06 were characterized by significant decreases in foraminiferal density, S, E, and H, relative to the down-core intervals as well as previous surveys. Non-metric multidimensional scaling (nMDS) analysis suggested that a 3-fold increase in polycyclic aromatic hydrocarbon (PAH) concentration in the surface interval, relative to the down-core interval, was the environmental driver of benthic foraminiferal variability. These records suggested that the benthic foraminiferal recovery time, following an event such as the DWH, was on the order of 1-2 years.

Severe blunt thoracic trauma: differences between adults and children in a level I trauma centre.

BACKGROUND: Trauma is a leading cause of death in the developing world. Blunt thoracic trauma represents a major burden of disease in both adults and children. Few studies have investigated the differences between these two patient groups. OBJECTIVE: To compare mechanism of injury, presentation, management and outcome in children and adults with blunt thoracic trauma. METHODS: Patients were identified from the database of the trauma intensive care unit at Inkosi Albert Luthuli Central Hospital, Durban, South Africa. Demographics and relevant data were extracted from a pre-existing database. RESULTS: Of 415 patients admitted to the unit, 331 (79.7%) were adults and 84 (20.2%) children aged < 18 years. The median injury severity score (ISS) was similar for both age groups (32 v. 34; p = 0.812). Adults had a higher lactate level at presentation (3.94 v. 2.60 mmol/L; p = 0.001). Of the children, 96.4% were injured in motor vehicle collisions, 75.0% as pedestrians. Compared with adults, children had significantly fewer rib fractures (20.2% v. 42.0%; p < 0.001), flail chests (2.4% v. 26.3%; p<0.001) and.blunt cardiac injuries (BCIs) (9.5% v. 23.6%; p = 0.004), but sustained more lung contusions (79.8% v. 65.6%; p = 0.013). Mortality in children was significantly lower than in adults (16.7% v. 27.8%; p = 0.037). CONCLUSION: Thoracic injuries in children are the result of pedestrian collisions more often than in adults. They suffer fewer rib fractures and BCIs, but more lung contusions. Despite similar ISSs, children have significantly lower mortality than adults. More effort needs to be concentrated on child safety and preventing pedestrian injury.

Direct admission versus inter-hospital transfer to a level I trauma unit improves survival: an audit of the new Inkosi Albert Luthuli Central Hospital trauma unit.

OBJECTIVE: To audit the performance of a new level I trauma unit and trauma intensive care unit. METHODS: Data on patients admitted to the level I trauma unit and trauma intensive care unit at Inkosi Albert Luthuli Central Hospital, Durban, from March 2007 to December 2008 were retrieved from the hospital informatics system and an independent database in the trauma unit. RESULTS: Four hundred and seven patients were admitted; 71% of admissions were inter-hospital transfers (IHT) and 29% direct from scene (DIR). The median age was 27 years (range 1 - 83), and 71% were male. Blunt injury accounted for 66.3% of admissions and penetrating trauma for 33.7%. Of the former, motor vehicle-related injury accounted for 87.4%, with 81% of paediatric admissions due to pedestrian-related injuries. The median injury severity score (ISS) for the entire cohort was 22 (survivors 18, deaths 29; p<0.001). Patients in the DIR group had a significantly higher mean ISS compared with the IHT group (DIR 25, IHT 20; p<0.02). The overall mortality rate was 26.3%. There were 37 deaths (31.1%) in the DIR group and 70 (24.3%) in the IHT group (p=0.19). In patients surviving more than 12 hours the overall mortality rate was 21.1% (DIR 13.7%, IHT 23.5%; p=0.042). CONCLUSIONS: Trauma is a major cause of premature death in the young. Despite a significantly higher median ISS in direct admissions, there was no difference in mortality. Of those surviving more than 12 hours, patients admitted directly had a significant decrease in mortality. Dedicated trauma units improve outcome in the critically injured.

Efficacy and tolerability of bimatoprost versus travoprost in patients previously on latanoprost: a 3-month, randomised, masked-evaluator, multicentre study.

AIM: To evaluate the efficacy and safety of replacing latanoprost with another prostaglandin analogue (PGA) in patients with glaucoma or ocular hypertension requiring additional intraocular pressure (IOP) lowering while on latanoprost. METHODS: Prospective, randomised, investigator-masked, multicentre clinical trial. Patients on latanoprost 0.005% monotherapy requiring additional IOP lowering discontinued latanoprost and were randomised to bimatoprost 0.03% (n = 131) or travoprost 0.004% (n = 135). IOP was measured at latanoprost-treated baseline and after 1 month and 3 months of replacement therapy. RESULTS: Baseline mean diurnal IOP on latanoprost was similar between groups. The mean diurnal IOP was significantly lower with bimatoprost than with travoprost at 1 month (p = 0.009) and 3 months (p = 0.024). Overall, 22.0% of bimatoprost patients versus 12.1% of travoprost patients achieved a > or =15% reduction in diurnal IOP from latanoprost-treated baseline at both months 1 and 3 (p = 0.033). At month 3, the additional mean diurnal IOP reduction from latanoprost-treated baseline was 2.1 (95% CI 1.7 to 2.5) mm Hg (11.0%) with bimatoprost and 1.4 (95% CI 0.9 to 1.8) mm Hg (7.4%) with travoprost (p = 0.024). At 3 months, 11.5% of bimatoprost and 16.5% of travoprost patients demonstrated a > or =1-grade increase in physician-graded conjunctival hyperaemia (p = 0.288). Hyperaemia was reported as a treatment-related adverse event in 3.1% of bimatoprost and 1.5% of travoprost patients (p = 0.445). CONCLUSION: Patients on latanoprost requiring lower IOP achieved a greater additional short-term diurnal IOP reduction when latanoprost was replaced by bimatoprost compared with travoprost. Low rates of hyperaemia were observed in patients treated with bimatoprost or travoprost after switching from latanoprost.

Resistance exercise effects on blood glutathione status and plasma protein carbonyls: influence of partial vascular occlusion.

Seven weight-trained males performed both light resistance with partial occlusion (LRO: 30% 1 RM) and moderate resistance (MR: 70% 1 RM) to failure to ascertain whether blood protein carbonyls (PC) and glutathione status was altered compared to partial occlusion (PO) in a counterbalanced fashion. PO was identical in duration to the LRO session and all sessions were on separate days. PC did not differ for the three conditions at PRE (0.05 nM mg protein(-1)). PC significantly increased for PO and MR over time and was greater than the LRO treatment at POST (0.13 nM mg protein(-1)). The GSSG/TGSH ratio at PRE did not differ across treatments (8%) whereas the ratio at POST was significantly elevated for PO and MR treatments (17%). In contrast, no change occurred for the LRO session at any time. These results indicate that MR to failure and PO can significantly increase blood oxidative stress but LRO did not elicit oxidative stress.