Summary
Background
Nonresponse and loss of response to anti‐TNF therapies in Crohn's disease represent significant clinical problems for which clear management guidelines are lacking.
Aim
To review ...the incidence, mechanisms and predictors of primary nonresponse and secondary loss of response to formulate practical clinical algorithms to guide management.
Methods
Through a systematic literature review, 503 articles were identified which fit the inclusion criteria.
Results
Primary nonresponse to anti‐TNF treatment affects 13–40% of patients. Secondary loss of response to anti‐TNF occurs in 23–46% of patients when determined according to dose intensification, and 5–13% of patients when gauged by drug discontinuation rates. Recent evidence suggests that the mechanisms underlying primary nonresponse and secondary loss of response are multifactorial and include disease characteristics (phenotype, location, severity); drug (pharmacokinetic, pharmacodynamic or immunogenicity) and treatment strategy (dosing regimen) related factors. Clinical algorithms that employ therapeutic drug monitoring (using anti‐TNF tough levels and anti‐drug antibody levels) may be used to determine the underlying cause of primary nonresponse and secondary loss of response respectively and guide clinicians as to which patients are most likely to respond to anti‐TNF therapy and help optimise drug therapy for those who are losing response to anti‐TNF therapy.
Conclusions
Nonresponse or loss of response to anti‐TNF occurs commonly in Crohn's disease. Clinical algorithms utilising therapeutic drug monitoring may establish the mechanisms for treatment failure and help guide the subsequent therapeutic approach.
Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of ...reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.
Summary
Background
Acute severe ulcerative colitis (ASUC) is a life‐threatening condition for which optimal management strategies remain ill‐defined.
Aim
To review the evidence regarding the natural ...history, diagnosis, monitoring and treatment of ASUC to inform an evidence‐based approach to management.
Methods
Relevant articles addressing the management of ASUC were identified from a search of MEDLINE, the Cochrane Library and conference proceedings.
Results
Of ASUC, 31–35% is steroid‐refractory. Infliximab and ciclosporin salvage therapies have improved patient outcomes in randomised controlled trials. Short‐term response rates (within 3 months) have ranged from 40% – 54% for ciclosporin and 46–83% for infliximab. Long‐term clinical response rates (≥1 year) have ranged from 42%–50% for ciclosporin and 50–65% for infliximab. Short‐term and long‐term colectomy rates have been respectively: 26–47% and 36–58% for ciclosporin, and 0–50% and 35–50% for infliximab. Mortality rates for ciclosporin and infliximab‐treated patients have been: 0–5% and 0–2%, respectively. At present, management challenges include the selection, timing and assessment of response to salvage therapy, utilisation of therapeutic drug monitoring and long‐term maintenance of remission.
Conclusions
Optimal management of acute severe ulcerative colitis should be guided by risk stratification using predictive indices of corticosteroid response. Timely commencement and assessment of response to salvage therapy is critical to reducing morbidity and mortality. Emerging pharmacokinetic models and therapeutic drug monitoring may assist clinical decision‐making and facilitate a shift towards individualised acute severe ulcerative colitis therapies.
Food fraud in herbs and spices is an important topic, which has led to new technologies being studied as potential tools for fraud identification. Nontargeted technologies have proven to be a useful ...tool for the authentication of herbs and spices. The present review focuses on the use of near‐infrared, hyperspectral imaging, Fourier‐transform infrared, Raman, nuclear magnetic resonance, and electron spin resonance spectroscopy for the authentication of spices, which includes the determination of origin and irradiated spices and the identification of adulterants. The methods developed based on vibrational spectroscopy combined with chemometric techniques seem to be promising tools for determining the presence of adulterants and contaminants in herbs and spices. On the other hand, nuclear magnetic resonance seems to be the most efficient technology to determine the origin of herbs and spices although, for some cases, studies with near‐infrared spectroscopy can be a viable substitute. Electron spin resonance spectroscopy is the technique par excellence used for the authentication of irradiated herbs and spices, so its use should be expanded to many more spices’ varieties. Portable devices are preferred by those involved in the food industry, due to its manageability and low cost. Data fusion and big data are shown as promising tools for spice fraud control. In conclusion, spectroscopic techniques show a great efficiency to authenticate spices, although their evaluation must be expanded to other spice varieties, to new strategies of data analysis (as data fusion and big data), and to the use of portable devices.
Abstract
Estuaries are highly productive ecosystems, which are strongly affected by several anthropogenic pressures. Phytoplankton is a key element for assessing the ecological quality status in ...these transitional waters. Moreover, understanding physico-chemical and biological drivers is crucial to disentangle their effect on the structure of phytoplankton community. The present work aims to study the effect of the main physico-chemical drivers on the phytoplankton community structure and dynamics in a temperate well-mixed estuary (Sado Estuary). Four sampling stations were analyzed monthly in three regions of the estuary, from 2018 to 2019. Surface water samples were collected to analyze the phytoplankton community and several concomitant physico-chemical parameters. Temperature, turbidity, salinity, and nutrients availability were the drivers that best explained the spatio-temporal patterns observed in the phytoplankton community. The upper estuary was characterized by higher phytoplankton cell abundances and biomass. Three phytoplankton groups stood out in the characterization of the estuarine assemblages: diatoms, cryptophytes, and dinoflagellates. Diatoms were the dominant group most of the year, being dominated by small cell species (single and chain-forming) upstream, and by larger chain-forming species downstream. Cryptophytes had a high contribution to the community in the inner regions of the estuary, while dinoflagellates contributed more for the community composition downstream, where high abundances of harmful algal species were sporadically found. Previous studies on the phytoplankton community dynamics in this estuary are limited to the 1990s. Thus, the present study provides insight into changes in the dominant phytoplankton groups of the Sado Estuary in the last 25 years, namely an increase in cryptophytes over diatoms in the inner estuarine regions, and an increase in dinoflagellates near the estuary mouth.
Recent studies report the immunomodulatory lung-protective role of halogenated anaesthetics during lung resection surgery (LRS) but have not investigated differences in clinical postoperative ...pulmonary complications (PPCs). The main goal of the present study was to compare the effect of sevoflurane and propofol on the incidence of PPCs in patients undergoing LRS. The second aim was to compare pulmonary and systemic inflammatory responses to LRS.
Of 180 patients undergoing LRS recruited, data from 174 patients were analysed. Patients were randomized to two groups (propofol or sevoflurane) and were managed otherwise using the same anaesthetic protocol. Bronchoalveolar lavage (BAL) was performed in both lungs before and after one-lung ventilation for analysis of cytokines. Arterial blood was drawn for measurement of the cytokines analysed in the BAL fluid at five time points. Intraoperative haemodynamic and respiratory parameters, PPCs (defined following the ARISCAT study), and mortality during the first month and yr were recorded.
More PPCs were detected in the propofol group (28.4% vs 14%, OR 2.44 95% CI, 1.14–5.26). First-yr mortality was significantly higher in the propofol group (12.5% vs 2.3%, OR 5.37 95% CI, 1.23–23.54). Expression of lung and systemic pro-inflammatory cytokines was greater in the propofol group than in the sevoflurane group. Pulmonary and systemic IL-10 release was less in the propofol group.
Our results suggest that administration of sevoflurane during LRS reduces the frequency of the PPCs recorded in our study and attenuates the pulmonary and systemic inflammatory response.
NCT 02168751; EudraCT 2011-002294-29.
We demonstrate the room-temperature control of magnetization reversal with an electric field in an epitaxial nanostructure consisting of ferrimagnetic nanopillars embedded in a ferroelectric matrix. ...This was achieved by combining a weak, uniform magnetic field with the switching electric field to selectively switch pillars with only one magnetic configuration. On the basis of these experimental results, we propose to use an electric field to assist magnetic recording in multiferroic systems with high perpendicular magnetic anisotropy.
Summary
Background
Excessive visceral adipose tissue has been associated with poorer outcomes in patients with inflammatory bowel disease.
Aim
To determine whether body composition is associated with ...outcome in a prospective study of post‐operative Crohn's disease patients.
Methods
The POCER study evaluated management strategies for prevention of post‐operative Crohn's disease recurrence; subjects were enrolled after resection of all macroscopic Crohn's disease and were randomised to early endoscopy and possible treatment escalation, or standard care. The primary endpoint was endoscopic recurrence at 18 months. 44 subjects with cross‐sectional abdominal imaging were studied, and body composition analysis performed using established techniques to measure visceral adipose tissue area, subcutaneous adipose tissue area, and skeletal muscle area.
Results
The body composition parameter with the greatest variance was visceral adipose tissue. Regardless of treatment, all subjects with visceral adipose tissue/height2 >1.5 times the gender‐specific mean experienced endoscopic recurrence at 18 months (compared to 47%) relative risk 2.1, 95% CI 1.5–3.0, P = 0.012. Waist circumference correlated strongly with visceral adipose tissue area (ρ = 0.840, P < 0.001). Low skeletal muscle was prevalent (41% of patients), but did not predict endoscopic recurrence; however, appendicular skeletal muscle indices correlated inversely with faecal calprotectin (ρ = 0.560, P = 0.046).
Conclusions
Visceral adiposity is an independent risk factor for endoscopic recurrence of Crohn's disease after surgery. Sarcopenia correlates with inflammatory biomarkers. Measures of visceral adipose tissue may help to stratify risk in post‐operative management strategies.
Linked ContentThis article is linked to Holt et al, and Stidham and Waljee papers. To view these articles visit https://doi.org/10.1111/apt.14102 and https://doi.org/10.1111/apt.14069.
To establish effective water quality monitoring strategies in estuaries, it is imperative to identify and understand the main drivers for the variation of water quality parameters. The tidal effect ...is an important factor of the daily and fortnightly variability in several estuaries. However, the extent of that influence on the different physicochemical and biological parameters is still overlooked in some estuarine systems, such as the Sado Estuary, a mesotidal estuary located on the west coast of Portugal. The main objective of this study was to determine how the water quality parameters of the Sado Estuary varied with the fortnightly and the semidiurnal tidal variation. To achieve this goal, sampling campaigns were conducted in May/18, Nov/18 and Jun/19, under neap and spring tidal conditions, with data collection over the tidal cycle. Results were observed to be significantly influenced by the tidal variation, in a large area of the estuary. Flood seemed to mitigate possible effects of nutrient enrichment in the water column. Additionally, significant differences were also observed when considering the different sampling stations. Temperature, Suspended Particulate Matter (SPM) and nutrients showed the highest values at low water. Lastly, the implications of the tidal variability in the evaluation of the water quality according to Water Framework Directive were also discussed, highlighting the importance of studying short-time scale variations and the worst-case scenario to ensure water quality is maintained. These findings are relevant for the implementation of regional management plans and to promote sustainable development.
The increasing demand on diagnostic assays that are sensitive and specific for pathogenic antibodies, and the interest in identifying new antigens, prompted the development of cell-based assays for ...the detection of autoantibodies in myasthenia gravis and other autoimmune disorders. Cell-based assays were initially used to show that clustering the AChR improved the positivity in myasthenia gravis, and similar assays have now been applied to detection of antibodies to neuromuscular junction candidate proteins such as LRP4 and agrin. In addition cell-based assays have been used in the routine detection of antibodies to proteins expressed on the surface of neurons (NMDAR, LGI1, CASPR2, AMPAR, GABA-A/B, GlyR, and DPPX) and glia (AQP4, MOG). Here, we summarize the findings in myasthenia and discuss the advantages, disadvantages and controversial issues of using cell-based assays in the detection of these antibodies, and their relevance to the testing of preclinical models of disease.
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