There are currently two million cancer survivors in the United Kingdom, and in recent years this number has grown by 3% per annum. The aim of this paper is to provide long-term projections of cancer ...prevalence in the United Kingdom.
National cancer registry data for England were used to estimate cancer prevalence in the United Kingdom in 2009. Using a model of prevalence as a function of incidence, survival and population demographics, projections were made to 2040. Different scenarios of future incidence and survival, and their effects on cancer prevalence, were also considered. Colorectal, lung, prostate, female breast and all cancers combined (excluding non-melanoma skin cancer) were analysed separately.
Assuming that existing trends in incidence and survival continue, the number of cancer survivors in the United Kingdom is projected to increase by approximately one million per decade from 2010 to 2040. Particularly large increases are anticipated in the oldest age groups, and in the number of long-term survivors. By 2040, almost a quarter of people aged at least 65 will be cancer survivors.
Increasing cancer survival and the growing/ageing population of the United Kingdom mean that the population of survivors is likely to grow substantially in the coming decades, as are the related demands upon the health service. Plans must, therefore, be laid to ensure that the varied needs of cancer survivors can be met in the future.
This review presents an update on the current knowledge of the secondary metabolite potential of the major fungal species used in industrial biotechnology, i.e.,
Aspergillus niger
,
Aspergillus ...oryzae
, and
Trichoderma reesei
. These species have a long history of safe use for enzyme production. Like most microorganisms that exist in a challenging environment in nature, these fungi can produce a large variety and number of secondary metabolites. Many of these compounds present several properties that make them attractive for different industrial and medical applications. A description of all known secondary metabolites produced by these species is presented here. Mycotoxins are a very limited group of secondary metabolites that can be produced by fungi and that pose health hazards in humans and other vertebrates when ingested in small amounts. Some mycotoxins are species-specific. Here, we present scientific basis for (1) the definition of mycotoxins including an update on their toxicity and (2) the clarity on misclassification of species and their mycotoxin potential reported in literature, e.g.,
A. oryzae
has been wrongly reported as an aflatoxin producer, due to misclassification of
Aspergillus flavus
strains. It is therefore of paramount importance to accurately describe the mycotoxins that can potentially be produced by a fungal species that is to be used as a production organism and to ensure that production strains are not capable of producing mycotoxins during enzyme production. This review is intended as a reference paper for authorities, companies, and researchers dealing with secondary metabolite assessment, risk evaluation for food or feed enzyme production, or considerations on the use of these species as production hosts.
Obesity surgery and risk of cancer Mackenzie, H.; Markar, S. R.; Askari, A. ...
British journal of surgery,
November 2018, Letnik:
105, Številka:
12
Journal Article
Recenzirano
Odprti dostop
Background
Obesity increases the risk of several types of cancer. Whether bariatric surgery influences the risk of obesity‐related cancer is not clear. This study aimed to uncover the risk of ...hormone‐related (breast, endometrial and prostate), colorectal and oesophageal cancers following obesity surgery.
Methods
This national population‐based cohort study used data from the Hospital Episode Statistics database in England collected between 1997 and 2012. Propensity matching on sex, age, co‐morbidity and duration of follow‐up was used to compare cancer risk among obese individuals undergoing bariatric surgery (gastric bypass, gastric banding or sleeve gastrectomy) and obese individuals not undergoing such surgery. Conditional logistic regression provided odds ratios (ORs) with 95 per cent confidence intervals.
Results
In the study period, from a cohort of 716 960 patients diagnosed with obesity, 8794 patients who underwent bariatric surgery were matched exactly with 8794 obese patients who did not have surgery. Compared with the no‐surgery group, patients who had bariatric surgery exhibited a decreased risk of hormone‐related cancers (OR 0·23, 95 per cent c.i. 0·18 to 0·30). This decrease was consistent for breast (OR 0·25, 0·19 to 0·33), endometrium (OR 0·21, 0·13 to 0·35) and prostate (OR 0·37, 0·17 to 0·76) cancer. Gastric bypass resulted in the largest risk reduction for hormone‐related cancers (OR 0·16, 0·11 to 0·24). Gastric bypass, but not gastric banding or sleeve gastrectomy, was associated with an increased risk of colorectal cancer (OR 2·63, 1·17 to 5·95). Longer follow‐up after bariatric surgery strengthened these diverging associations.
Conclusion
Bariatric surgery is associated with decreased risk of hormone‐related cancers, whereas gastric bypass might increase the risk of colorectal cancer.
Obesity affects cancer risk
Summary
Background
Activation of Kupffer cells may be involved in the pathogenesis of portal hypertension by release of vasoconstrictive substances and fibrosis due to co‐activation of hepatic ...stellate cells.
Aim
To study soluble plasma (s) CD163, a specific marker of activated macrophages, as a biomarker for portal hypertension in patients with liver cirrhosis.
Methods
We measured sCD163 concentration and the hepatic venous pressure gradient (HVPG) by liver vein catheterisation in 81 cirrhosis patients (Child–Pugh CP‐A: n = 26, CP‐B: n = 29, CP‐C: n = 26) and 22 healthy subjects. We also measured their cardiac output (CO), cardiac index and systemic vascular resistance (SVR). Liver status was examined by Child–Pugh and MELD‐score.
Results
In cirrhosis, sCD163 concentration was nearly three times higher than in controls (4.7 ± 2.5 vs. 1.6 ± 0.5 mg/L, P < 0.001). sCD163 was also higher, as measured in steps by CP‐score (P < 0.001). The HVPG rose steeply to an asymptote of 22 mmHg with sCD163 up to about 5 mg/L and not to higher values with higher sCD163. In a multivariate analysis, sCD163 was the only independent predictor of the HVPG but did not predict any of the systemic circulatory findings. sCD163 > 3.95 mg/L (upper normal limit) predicted HVPG ≥ 10 mmHg with a positive predictive value of 0.99.
Conclusions
Circulating sCD163 originating from activated Kupffer cells is increased in cirrhosis with increasing Child–Pugh score and with increasing HVPG, and it is an independent predictor for HVPG. These findings support a primary role of macrophage activation in portal hypertension, and may indicate a target for biological intervention.
Systematic review of studies investigating interleukin‐18 (IL‐18) in hemophagocytic lymphohistiocytosis (HLH) and macrophage activation syndrome (MAS).Serum IL‐18 appears to discriminate well between ...HLH/MAS and other inflammatory conditions.
Summary
Hemophagocytic lymphohistiocytosis (HLH) is a life‐threatening, hyperinflammatory disorder, characterized by multiorgan failure, fever and cytopenias. The diagnosis of HLH and its subtype Macrophage Activation Syndrome (MAS) remains a challenge. Interleukin 18 (IL‐18) is emerging as a potential biomarker for HLH/MAS but is currently not a part of diagnostic criteria. This systematic review aimed to assess the potential role of IL‐18 in the diagnosis and monitoring of HLH and MAS, and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. PubMed and Embase were searched on 30 January 2020. Studies included all subtypes of HLH and a range of underlying disorders in both children and adults. A total of 14 studies were included. Generally, serum IL‐18 was elevated in both primary and secondary HLH (> 1000 pg/ml) compared with other inflammatory conditions and with healthy individuals; thus, serum IL‐18 may be able to discriminate between HLH and other inflammatory conditions. Significantly increased IL‐18 (> 10 000 pg/ml) was also consistently described in MAS compared with other subtypes of HLH. The ability of IL‐18 to distinguish MAS from systemic juvenile idiopathic arthritis (JIA) is less unambiguous, as IL‐18 levels > 100 000 pg/ml were described in sJIA patients both with and without MAS. IL‐18 may help to differentiate between HLH subtypes and other inflammatory conditions. As HLH and MAS are rare disorders, only few and relatively small studies exist on the subject. Larger, prospective multi‐center studies are called for to assess the diagnostic precision of IL‐18 for HLH and MAS.
Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease. Studies suggest that pro-inflammatory cytokines may be attenuated by the vagus nerve through the cholinergic ...anti-inflammatory pathway. We aimed to evaluate the anti-inflammatory effects of short-term transcutaneous non-invasive vagus nerve stimulation (n-VNS) applied to the cervical vagus nerve in patients with RA.
Method: We conducted a single-centre, open-label, preliminary proof-of-concept study of n-VNS in two cohorts of participants with RA: one with high disease activity (n = 16) and one with low disease activity (n = 20). Disease Activity Score based on 28-joint count-C-reactive protein (DAS28-CRP), cardiac vagal tone, and pro-inflammatory cytokines were measured at baseline and after 1 and 4 days of n-VNS.
Results: In the high disease activity group, n-VNS resulted in reductions in DAS28-CRP (4.1 to 3.8, p = 0.02), CRP (8.2 to 6 mg/mL, p = 0.01), and interferon-γ (29.8 to 22.5 pg/mL, p = 0.02). In the low disease activity group, there was no effect on DAS28-CRP, and n-VNS was associated with a decrease in cardiac vagal tone (p = 0.03) and a reduction in interleukin-10 (0.8 to 0.6 pg/mL, p = 0.02). Participants with high disease activity had lower baseline cardiac vagal tone than those with low disease activity (3.6 ± 2 vs 4.9 ± 3 linear vagal scale, p = 0.03). Cardiac vagal tone was negatively associated with DAS28-CRP (r = −0.37, p = 0.03). Overall, n-VNS was well tolerated.
Conclusion: This study provides preliminary support for an anti-inflammatory effect of n-VNS in patients with RA. These findings warrant further investigation in larger placebo-controlled trials.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Background
Morbidity and mortality following perforated peptic ulcer (PPU) remain substantial. Surgical delay is a well established negative prognostic factor, but evidence derives from studies with ...a high risk of bias. The aim of the present nationwide cohort study was to evaluate the adjusted effect of hourly surgical delay on survival after PPU.
Methods
This was a cohort study including all Danish patients treated surgically for PPU between 1 February 2003 and 31 August 2009. Medically treated patients and those with a malignant ulcer were excluded. The associations between surgical delay and 30‐day survival are presented as crude and adjusted relative risks (RRs) with 95 per cent confidence intervals (c.i.).
Results
A total of 2668 patients were included. Their median age was 70·9 (range 16·2–104·2) years and 55·4 per cent (1478 of 2668) were female. Some 67·5 per cent of the patients (1800 of 2668) had at least one of six co‐morbid diseases and 45·6 per cent had an American Society of Anesthesiologists fitness grade of III or more. A total of 708 patients (26·5 per cent) died within 30 days of surgery. Every hour of delay from admission to surgery was associated with an adjusted 2·4 per cent decreased probability of survival compared with the previous hour (adjusted RR 1·024, 95 per cent c.i. 1·011 to 1·037).
Conclusion
Limiting surgical delay in patients with PPU seems of paramount importance.
Minimize delay before surgery
The aim of this Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) is to formulate an evidence-based guidance for the use of neuromuscular blocking agents (NMBA) in adults with acute ...respiratory distress syndrome (ARDS). The panel comprised 20 international clinical experts from 12 countries, and 2 patient representatives. We adhered to the methodology for trustworthy clinical practice guidelines and followed a strict conflict of interest policy. We convened panelists through teleconferences and web-based discussions. Guideline experts from the guidelines in intensive care, development, and evaluation Group provided methodological support. Two content experts provided input and shared their expertise with the panel but did not participate in drafting the final recommendations. We followed the Grading of Recommendations Assessment, Development, and Evaluation approach to assess the certainty of evidence and grade recommendations and suggestions. We used the evidence to decision framework to generate recommendations. The panel provided input on guideline implementation and monitoring, and suggested future research priorities. The overall certainty in the evidence was low. The ICM-RPG panel issued one recommendation and two suggestions regarding the use of NMBAs in adults with ARDS. Current evidence does not support the early routine use of an NMBA infusion in adults with ARDS of any severity. It favours avoiding a continuous infusion of NMBA for patients who are ventilated using a lighter sedation strategy. However, for patients who require deep sedation to facilitate lung protective ventilation or prone positioning, and require neuromuscular blockade, an infusion of an NMBA for 48 h is a reasonable option.
Background
Stress ulcer prophylaxis (SUP) may decrease the incidence of gastrointestinal bleeding in patients in the intensive care unit (ICU), but the risk of infection may be increased. In this ...study, we aimed to describe SUP practices in adult ICUs. We hypothesised that patient selection for SUP varies both within and between countries.
Methods
Adult ICUs were invited to participate in the survey. We registered country, type of hospital, type and size of ICU, preferred SUP agent, presence of local guideline, reported indications for SUP, criteria for discontinuing SUP, and concerns about adverse effects. Fisher's exact test was used to assess differences between groups.
Results
Ninety‐seven adult ICUs in 11 countries participated (eight European). All but one ICU used SUP, and 64% (62/97) reported having a guideline for the use of SUP. Proton pump inhibitors were the most common SUP agent, used in 66% of ICUs (64/97), and H2‐receptor antagonists were used 31% (30/97) of the units. Twenty‐three different indications for SUP were reported, the most frequent being mechanical ventilation. All patients were prescribed SUP in 26% (25/97) of the ICUs. Adequate enteral feeding was the most frequent reason for discontinuing SUP, but 19% (18/97) continued SUP upon ICU discharge. The majority expressed concern about nosocomial pneumonia and Clostridium difficile infection with the use of SUP.
Conclusions
In this international survey, most participating ICUs reported using SUP, primarily proton pump inhibitors, but many did not have a guideline; indications varied considerably and concern existed about infectious complications.
Atmospheric Autoxidation of Amines Møller, Kristian H; Berndt, Torsten; Kjaergaard, Henrik G
Environmental science & technology,
09/2020, Letnik:
54, Številka:
18
Journal Article
Recenzirano
Autoxidation has been acknowledged as a major oxidation pathway in a broad range of atmospherically important compounds including isoprene, monoterpenes, and very recently, dimethyl sulfide. Here, we ...present a high-level theoretical multiconformer transition-state theory study of the atmospheric autoxidation in amines exemplified by the atmospherically important trimethylamine (TMA) and dimethylamine and generalized by the study of the larger diethylamine. Overall, we find that the initial hydrogen shift reactions have rate coefficients greater than 0.1 s–1 and autoxidation is thus an important atmospheric pathway for amines. This autoxidation efficiently leads to the formation of hydroperoxy amides, a new type of atmospheric nitrogen-containing compounds, and for TMA, we experimentally confirm this. The conversion of amines to hydroperoxy amides may have important implications for nucleation and growth of atmospheric secondary organic aerosols and atmospheric OH recycling.
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