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The survival of acute myeloid leukaemia (AML) patients aged over 60 has been suboptimal historically, whether they are treated using hypomethylating agents, low-dose cytarabine (LDAC) or venetoclax-based regimens. Progress is being made, however, for subgroups with favourable molecular or cytogenetic findings. Arginine metabolism plays a key role in AML pathophysiology. We report the only randomised study of LDAC with recombinant arginase BCT-100 versus LDAC alone in older AML patients unsuitable for intensive therapy. Eighty-three patients were randomised to the study. An overall response rate was seen in 19.5% (all complete remission [CR]) and 15% (7.5% each in CR and CR without evidence of adequate count recovery [CRi]) of patients in the LDAC+BCT-100 and LDAC arms respectively (odds ratio 0.73, confidence interval 0.23-2.33; p = 0.592). No significant difference in overall or median survival between treatment arms was seen. The addition of BCT-100 to LDAC was well tolerated.

The diagnosis of mild traumatic brain injury or sports-related concussion is a challenge for all clinicians, players, coaches and parents involved in contact sports. Currently, there is no validated objective biomarker available to assess the presence or severity of concussion in sport, and so it is necessary to rely on subjective measures like self-reporting of symptoms which depend on the cooperation of the athlete. There is a significant health risk associated with repetitive injury if the diagnosis is missed, and so there is great value in an objective biomarker to assist diagnostic and prognostic decisions. To establish a panel of non-invasive MicroRNA biomarkers in urine and saliva for the rapid diagnosis of sports-related concussion and investigate the kinetics and clinical utility of these biomarkers in assisting diagnostic, prognostic and return-to-play decisions. Observational, prospective, multicentre cohort study recruiting between the 2017-2018 and 2018-2019 Rugby Union seasons. Professional rugby players in the two highest tiers of senior professional domestic rugby competition in England will be recruited prospectively to the study. During the season, three groups will be identified: athletes entering the World Rugby Head Injury Assessment (HIA) protocol, uninjured control athletes and control athletes with musculoskeletal injuries. Saliva and urine will be collected from these athletes at multiple timepoints, coinciding with key times in the HIA protocol and return-to-play process. Ethics approval has been obtained. The compiled and analysed results will be presented at national and international conferences concerning the care of patients with traumatic brain injury. Results will also be submitted for peer review and publication in the subject journals/literature. [Abstract copyright: © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.]

Traumatic brain injury (TBI) is a serious problem that causes high morbidity and mortality around the world. Currently, no reliable biomarkers are used to assess the severity and predict the recovery. Many protein biomarkers were extensively studied for diagnosis and prognosis of different TBI severities such as S-100β, glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE), neurofilament light chain (NFL), cleaved tau protein (C-tau), and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, none of these candidates is currently used in the clinical practice, due to relatively low sensitivity, for the diagnosis of mild TBI (mTBI) or mild to moderate TBI (MMTBI) patients who are clinically well and do not have a detectable intracranial pathology on the scans. MicroRNAs (miRNAs or miRs) are a class of small endogenous molecular regulators, which showed to be altered in different pathologies, including TBI and for this reason, their potential role in diagnosis, prognosis and therapeutic applications, is explored. Promising miRNAs such as miR-21, miR-16 or let-7i were identified as suitable candidate biomarkers for TBI and can differentiate mild from severe TBI. Also, they might represent new potential therapeutic targets. Identification of miRNA signature in tissue or biofluids, for several pathological conditions, is now possible thanks to the introduction of new high-throughput technologies such as microarray platform, Nanostring technologies or Next Generation Sequencing. This review has the aim to describe the role of microRNA in TBI and to explore the most commonly used techniques to identify microRNA profile. Understanding the strengths and limitations of the different methods can aid in the practical use of miRNA profiling for diverse clinical applications, including the development of a point-of-care device.

Rivers host a wealth of biodiversity and play critical ecological functions, so monitoring their environmental status and tracking its changes has paramount importance for appropriate management. Although some biological groups, and especially benthic macroinvertebrates, are employed routinely to achieve this goal, the quest for bioindicators of river quality is far from over, because finding further suitable organisms may improve indication performances and inform habitat management. Using organisms that are at risk for bioindication also fulfills the goal of providing important information for the conservation of the taxon (or taxa) used for bioindication. Bats are a diverse, threatened mammal group whose characteristics make them potentially suitable bioindicators in many ecosystem types, but research in this field is still limited. In this study, set in Central and Southern Italy, we hypothesize that assemblages of foraging bats will respond to environmental status and quality of riverine ecosystems and that therefore bats may serve as effective bioindicators. We established the environmental status of 50 sampling sites selected along 10 rivers using two indices officially adopted in the country, i.e. the STAR_ICMi (evaluating water quality from macrobenthic invertebrate assemblages) and the fluvial functionality index (Indice di Funzionalita Fluviale, IFF), which incorporates several biotic and abiotic components and represents a functional indicator of river ecosystem health. At the sampling sites, we also recorded bat activity with operator-independent real-time bat recorders and classified bat passes to species or phonic groups. We examined 167,371 macroinvertebrates and 55,157 bat passes, corresponding to 15 species or phonic groups. The activity of Miniopterus schreibersii/Pipistrellus pygmaeus and Myotis daubentonii/capaccinii declined with increasing values of STAR_ICMi and IFF, while the activity of Nyctalus/Eptesicus serotinus increased with both indices. The activity of P. kuhlii also declined as IFF values increased, while we observed the opposite for Pipistrellus pipistrellus, Myotis emarginatus, Myotis nattereri and Barbastella barbastellus. Pooling together species whose activity respectively increased or decreased as the values of quality indices increased improved indication performances by strengthening statistical significance. Our work constitutes a significant step towards the use of bats as bioindicators in river ecosystems as we show that differences in bat activity may reveal changes in environmental conditions and may thus demonstrate the effects of habitat alteration on the river biota. We highlight that locally adapted bat populations may show differences in foraging behaviour and food preferences; hence our findings warrant confirmation from other regions. Further constraints are given by the variable degree of taxonomic resolution achieved in bat sound analysis, which may represent an issue especially in species-rich bat assemblages such as those of southern Europe.