Activity

Technical success was achieved in all cases. Adverse events were border-line significantly more common in the Group

4/7 (57%) (pain n=3; pain and rectal bleeding n=1) compared with the Group

0/5 (0%), p=0.08, which resulted in preterm termination of the study. The clinical success rate was Group

6/7 (86%) vs Group

1/5 (20%), p=0.07.

Patients with strictures related to Crohn’s disease may benefit from treatment with self-expandable metal stents rather than dilatation. However, there seems to be an increased risk for patient pain after stenting, which has to be considered and handled.

The study was registered at Clinical Trials (NCT04718493).

The study was registered at Clinical Trials (NCT04718493).Inflammatory bowel diseases such as ulcerative colitis (UC) may be complicated by several extraintestinal manifestations. These involve joints, skin, eyes and less commonly lungs and heart. Myocarditis may result from the toxic effect of drugs (ie, mesalazine) commonly used for the treatment of UC or due to infections (eg, Coxsackieviruses, enteroviruses, adenovirus). Here, we report a case of a 26-year old man affected by UC and complicated by two episodes of myocarditis. Both episodes occurred during two severe exacerbations of UC. However, in both cases the aetiology of myocarditis remains uncertain being ascribable to extraintestinal manifestation, drug toxicity or both.Understanding energy use is central to understanding an animal’s physiological and behavioural ecology. However, directly measuring energy expenditure in free-ranging animals is inherently difficult. The doubly labelled water (DLW) method is widely used to investigate energy expenditure in a range of taxa. Although reliable, DLW data collection and analysis is both financially costly and time consuming. Dynamic body acceleration (e.g. VeDBA) calculated from animal-borne accelerometers has been used to determine behavioural patterns, and is increasingly being used as a proxy for energy expenditure. Still its performance as a proxy for energy expenditure in free-ranging animals is not well established and requires validation against established methods. In the present study, the relationship between VeDBA and the at-sea metabolic rate calculated from DLW was investigated in little penguins (Eudyptula minor) using three approaches. Both in a simple correlation and activity-specific approaches were shown to be good predictors of at-sea metabolic rate. The third approach using activity-specific energy expenditure values obtained from literature did not accurately calculate the energy expended by individuals. However, all three approaches were significantly strengthened by the addition of mean horizontal travel speed. These results provide validation for the use of accelerometry as a proxy for energy expenditure and show how energy expenditure may be influenced by both individual behaviour and environmental conditions.

To assess the accuracy of real-time telemedicine to diagnose and manage paediatric eye conditions.

Prospective, non-inferiority study analysing agreement in diagnoses and management plans between telemedicine and in-person examinations.

Paediatric ophthalmology clinic.

Children 0-17 years, English-speaking or Spanish-speaking, able to participate in age-appropriate manner, either previously seen by the optometrist and required ophthalmology referral or newly referred from outside source.

Paediatric optometrist conducted examinations using digital equipment and streamed live to a paediatric ophthalmologist who recorded diagnoses and management plans, then re-examined patients in-person. Subjects were masked to the fact they would see the ophthalmologist in-person, same-day.

Discrepancy in management plan or diagnosis between telemedicine and in-person examinations. Non-inferiority threshold was <1.5% for management plan or <15% for diagnosis discrepancies.

210 patients participated in n ophthalmologists and optometrists using this technology.Specific mutations in the RET proto-oncogene are associated with multiple endocrine neoplasia type 2A, a hereditary syndrome characterized by tumorigenesis in multiple glandular elements. In rare instances, MEN2A-associated germline RET mutations have also occurred with non-MEN2A associated cancers. SB203580 in vivo One such germline mutant RET mutation occurred concomitantly in a young adult diagnosed with alveolar rhabdomyosarcoma, a pediatric and young adult soft-tissue cancer with a generally poor prognosis. Although tumor tissue samples were initially unable to provide a viable cell culture for study, tumor tissues were sequenced for molecular characteristics. Through a hierarchical clustering approach, the index case sample was matched to several genetically similar cell models, which were transformed to express the same mutant RET as the index case and used to explore potential therapeutic options for mutant RET-bearing alveolar rhabdomyosarcoma. We also determined whether the RET mutation associated with the index case caused synthetic lethality to select clinical agents. From our investigation, we did not identify synthetic lethality associated with the expression of that patient’s RET variant, and overall we did not find experimental evidence for the role of RET in rhabdomyosarcoma progression.Immunotherapeutic manipulation of the antitumor immune response offers an attractive strategy to target genomic instability in cancer. A subset of tumor-specific somatic mutations can be translated into immunogenic and HLA-bound epitopes called neoantigens, which can induce the activation of helper and cytotoxic T lymphocytes. However, cancer immunoediting and immunosuppressive mechanisms often allow tumors to evade immune recognition. Recent evidence also suggests that the tumor neoantigen landscape extends beyond epitopes originating from nonsynonymous single-nucleotide variants in the coding exome. Here we review emerging approaches for identifying, prioritizing, and immunologically targeting personalized neoantigens using polyvalent cancer vaccines and T-cell receptor gene therapy. SIGNIFICANCE Several major challenges currently impede the clinical efficacy of neoantigen-directed immunotherapy, such as the relative infrequency of immunogenic neoantigens, suboptimal potency and priming of de novo tumor-specific T cells, and tumor cell-intrinsic and -extrinsic mechanisms of immune evasion.