Haemostatics in surgery and our experience in the enucleoresection of renal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>30 patients, with T1 renal cell carcinomas (RCC) who underwent open enucleoresection of the tumour, were randomized to the use of a topical haemostatic agent (Floseal) or to an infrared-sapphire coagulator (ISC), to compare their efficacy in achieving haemostasis. Methods: Successful intra-operative haemostasis, intra- and post-operative bleeding, operative time, hospital discharge were evaluated.</p> <p>Results</p> <p>Statistically higher rates of successful haemostasis and shorter time-to-haemostasis (8,1 vs 12,9 min) were observed in the FloSeal group (p < 0.001 both). Patients operative time was not different between Group 1 vs 2 (58.7 ± 12 vs 62.4 ± 15; p > 0.05). The average blood loss during surgery was less (60 +/- 25.5 mL) for the FloSeal group than for the ISC group (85 +/- 40.5 mL) (p < 0.05). Postoperative blood loss was 25 +/- 5 mL and 40 +/- 45 mL for Floseal and ISC respectively, (p < 0.05). Length of the postoperative hospital discharge was 2.5 +/- 1.2 days for FloSeal group and 3.5 +/- 1.3 for the Group 2 (p < 0.05). No major immediate or delayed complications were observed in either Groups.</p> <p>Conclusions</p> <p>The use of Floseal and ISC offer a safe and efficacy haemostasis in the enucleoresection of RCC. Moreover, our results show a less intra-operative and post-operative blood loss as well as a shorter time to haemostasis of Floseal in respect to ISC.</p

High Post-Capture Survival for Sharks, Rays and Chimaeras Discarded in the Main Shark Fishery of Australia?

Most sharks, rays and chimaeras (chondrichthyans) taken in commercial fisheries are discarded (i.e. returned to the ocean either dead or alive). Quantifying the post-capture survival (PCS) of discarded species is therefore essential for the improved management and conservation of this group. For all chondrichthyans taken in the main shark fishery of Australia, we quantified the immediate PCS of individuals reaching the deck of commercial shark gillnet fishing vessels and applied a risk-based method to semi-quantitatively determine delayed and total PCS. Estimates of immediate, delayed and total PCS were consistent, being very high for the most commonly discarded species (Port Jackson shark, Australian swellshark, and spikey dogfish) and low for the most important commercial species (gummy and school sharks). Increasing gillnet soak time or water temperature significantly decreased PCS. Chondrichthyans with bottom-dwelling habits had the highest PCS whereas those with pelagic habits had the lowest PCS. The risk-based approach can be easily implemented as a standard practice of on-board observing programs, providing a convenient first-step assessment of the PCS of all species taken in commercial fisheries

Accommodating Dynamic Oceanographic Processes and Pelagic Biodiversity in Marine Conservation Planning

Pelagic ecosystems support a significant and vital component of the ocean's productivity and biodiversity. They are also heavily exploited and, as a result, are the focus of numerous spatial planning initiatives. Over the past decade, there has been increasing enthusiasm for protected areas as a tool for pelagic conservation, however, few have been implemented. Here we demonstrate an approach to plan protected areas that address the physical and biological dynamics typical of the pelagic realm. Specifically, we provide an example of an approach to planning protected areas that integrates pelagic and benthic conservation in the southern Benguela and Agulhas Bank ecosystems off South Africa. Our aim was to represent species of importance to fisheries and species of conservation concern within protected areas. In addition to representation, we ensured that protected areas were designed to consider pelagic dynamics, characterized from time-series data on key oceanographic processes, together with data on the abundance of small pelagic fishes. We found that, to have the highest likelihood of reaching conservation targets, protected area selection should be based on time-specific data rather than data averaged across time. More generally, we argue that innovative methods are needed to conserve ephemeral and dynamic pelagic biodiversity

Genomic signatures of local adaptation reveal source-sink dynamics in a high gene flow fish species

Understanding source-sink dynamics is important for conservation management, particularly when climatic events alter species' distributions. Following a 2011 'marine heatwave' in Western Australia, we observed high recruitment of the endemic fisheries target species Choerodon rubescens, towards the cooler (southern) end of its distribution. Here, we use a genome wide set of 14 559 single-nucleotide polymorphisms (SNPs) to identify the likely source population for this recruitment event. Most loci (76%) showed low genetic divergence across the species' range, indicating high levels of gene flow and confirming previous findings using neutral microsatellite markers. However, a small proportion of loci showed strong patterns of differentiation and exhibited patterns of population structure consistent with local adaptation. Clustering analyses based on these outlier loci indicated that recruits at the southern end of C. rubescens' range originated 400 km to the north, at the centre of the species' range, where average temperatures are up to 3 °C warmer. Survival of these recruits may be low because they carry alleles adapted to an environment different to the one they now reside in, but their survival is key to establishing locally adapted populations at and beyond the range edge as water temperatures increase with climate change

The effects of warming on the ecophysiology of two co-existing kelp species with contrasting distributions

The northeast Atlantic has warmed significantly since the early 1980s, leading to shifts in species distributions and changes in the structure and functioning of communities and ecosystems. This study investigated the effects of increased temperature on two co-existing habitat-forming kelps: Laminaria digitata, a northern boreal species, and Laminaria ochroleuca, a southern Lusitanian species, to shed light on mechanisms underpinning responses of trailing and leading edge populations to warming. Kelp sporophytes collected from southwest United Kingdom were maintained under 3 treatments: ambient temperature (12 °C), +3 °C (15 °C) and +6 °C (18 °C) for 16 days. At higher temperatures, L. digitata showed a decline in growth rates and Fv/Fm, an increase in chemical defence production and a decrease in palatability. In contrast, L. ochroleuca demonstrated superior growth and photosynthesis at temperatures higher than current ambient levels, and was more heavily grazed. Whilst the observed decreased palatability of L. digitata held at higher temperatures could reduce top-down pressure on marginal populations, field observations of grazer densities suggest that this may be unimportant within the study system. Overall, our study suggests that shifts in trailing edge populations will be primarily driven by ecophysiological responses to high temperatures experienced during current and predicted thermal maxima, and although compensatory mechanisms may reduce top-down pressure on marginal populations, this is unlikely to be important within the current biogeographical context. Better understanding of the mechanisms underpinning climate-driven range shifts is important for habitat-forming species like kelps, which provide organic matter, create biogenic structure and alter environmental conditions for associated communities

Antiangiogenic therapy for breast cancer

Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria

Mechanisms and management of loss of response to anti-TNF therapy for patients with Crohn's disease: 3-year data from the prospective, multicentre PANTS cohort study

This is the final version. Available from Elsevier via the DOI in this record. Background We sought to report the effectiveness of infliximab and adalimumab over the first 3 years of treatment and to define the factors that predict anti-TNF treatment failure and the strategies that prevent or mitigate loss of response. Methods Personalised Anti-TNF therapy in Crohn’s disease (PANTS) is a UK-wide, multicentre, prospective observational cohort study reporting the rates of effectiveness of infliximab and adalimumab in anti-TNF-naive patients with active luminal Crohn’s disease aged 6 years and older. At the end of the first year, sites were invited to enrol participants still receiving study drug into the 2-year PANTS-extension study. We estimated rates of remission across the whole cohort at the end of years 1, 2, and 3 of the study using a modified survival technique with permutation testing. Multivariable regression and survival analyses were used to identify factors associated with loss of response in patients who had initially responded to anti-TNF therapy and with immunogenicity. Loss of response was defined in patients who initially responded to anti-TNF therapy at the end of induction and who subsequently developed symptomatic activity that warranted an escalation of steroid, immunomodulatory, or anti-TNF therapy, resectional surgery, or exit from study due to treatment failure. This study was registered with ClinicalTrials.gov, NCT03088449, and is now complete. Findings Between March 19, 2014, and Sept 21, 2017, 389 (41%) of 955 patients treated with infliximab and 209 (32%) of 655 treated with adalimumab in the PANTS study entered the PANTS-extension study (median age 32·5 years [IQR 22·1–46·8], 307 [51%] of 598 were female, and 291 [49%] were male). The estimated proportion of patients in remission at the end of years 1, 2, and 3 were, for infliximab 40·2% (95% CI 36·7–43·7), 34·4% (29·9–39·0), and 34·7% (29·8–39·5), and for adalimumab 35·9% (95% CI 31·2–40·5), 32·9% (26·8–39·2), and 28·9% (21·9–36·3), respectively. Optimal drug concentrations at week 14 to predict remission at any later timepoints were 6·1–10·0 mg/L for infliximab and 10·1–12·0 mg/L for adalimumab. After excluding patients who had primary non-response, the estimated proportions of patients who had loss of response by years 1, 2, and 3 were, for infliximab 34·4% (95% CI 30·4–38·2), 54·5% (49·4–59·0), and 60·0% (54·1–65·2), and for adalimumab 32·1% (26·7–37·1), 47·2% (40·2–53·4), and 68·4% (50·9–79·7), respectively. In multivariable analysis, loss of response at year 2 and 3 for patients treated with infliximab and adalimumab was predicted by low anti-TNF drug concentrations at week 14 (infliximab: hazard ratio [HR] for each ten-fold increase in drug concentration 0·45 [95% CI 0·30–0·67], adalimumab: 0·39 [0·22–0·70]). For patients treated with infliximab, loss of response was also associated with female sex (vs male sex; HR 1·47 [95% CI 1·11–1·95]), obesity (vs not obese 1·62 [1·08–2·42]), baseline white cell count (1·06 [1·02–1·11) per 1 × 10⁹ increase in cells per L), and thiopurine dose quartile. Among patients treated with adalimumab, carriage of the HLA-DQA1*05 risk variant was associated with loss of response (HR 1·95 [95% CI 1·17–3·25]). By the end of year 3, the estimated proportion of patients who developed anti-drug antibodies associated with undetectable drug concentrations was 44·0% (95% CI 38·1–49·4) among patients treated with infliximab and 20·3% (13·8–26·2) among those treated with adalimumab. The development of antidrug antibodies associated with undetectable drug concentrations was significantly associated with treatment without concomitant immunomodulator use for both groups (HR for immunomodulator use: infliximab 0·40 [95% CI 0·31–0·52], adalimumab 0·42 [95% CI 0·24–0·75]), and with carriage of HLA-DQA1*05 risk variant for infliximab (HR for carriage of risk variant: infliximab 1·46 [1·13–1·88]) but not for adalimumab (HR 1·60 [0·92–2·77]). Concomitant use of an immunomodulator before or on the day of starting infliximab was associated with increased time without the development of anti-drug antibodies associated with undetectable drug concentrations compared with use of infliximab alone (HR 2·87 [95% CI 2·20–3·74]) or introduction of an immunomodulator after anti-TNF initiation (1·70 [1·11–2·59]). In years 2 and 3, 16 (4%) of 389 patients treated with infliximab and 11 (5%) of 209 treated with adalimumab had adverse events leading to treatment withdrawal. Nine (2%) patients treated with infliximab and two (1%) of those treated with adalimumab had serious infections in years 2 and 3. Interpretation Only around a third of patients with active luminal Crohn’s disease treated with an anti-TNF drug were in remission at the end of 3 years of treatment. Low drug concentrations at the end of the induction period predict loss of response by year 3 of treatment, suggesting higher drug concentrations during the first year of treatment, particularly during induction, might lead to better long-term outcomes. Anti-drug antibodies associated with undetectable drug concentrations of infliximab, but not adalimumab, can be predicted by carriage of HLA-DQA1*05 and mitigated by concomitant immunomodulator use for both drugs.Guts UKCrohn’s and Colitis UKCure Crohn’s ColitisAbbVieMerck Sharp and DohmeNapp PharmaceuticalsPfizerCelltrion Healthcar