In order to detect the misuse of testosterone (T), urinary steroid concentrations and concentration ratios are quantified and monitored in a longitudinal manner to enable the identification of ...samples exhibiting atypical test results. These suspicious samples are then forwarded to isotope ratio mass spectrometry (IRMS)–based methods for confirmation. Especially concentration ratios like T over epitestosterone (E) or 5α-androstanediol over E proved to be valuable markers. Unfortunately, depending on the UGT2B17 genotype and/or the gender of the athlete, these markers may fail to provide evidence for T administrations when focusing exclusively on urine samples. In recent years, the potential of plasma steroids has been investigated and were found to be suitable to detect T administrations especially in female volunteers. A current drawback of this approach is the missing possibility to confirm that elevated steroid concentrations are solely derived from an administration of T and cannot be attributed to confounding factors. Therefore, an IRMS method for plasma steroids was developed and validated taking into account the comparably limited sample volume. As endogenous reference compounds, unconjugated cholesterol and dehydroepiandrosterone sulfate were found suitable, while androsterone and epiandrosterone (both sulfo-conjugated) were chosen as target analytes. The developed method is based on multi-dimensional gas chromatography coupled to IRMS in order to optimize the overall assay sensitivity. The approach was validated, and a reference population encompassing n = 65 males and females was investigated to calculate population-based thresholds. As proof-of-concept, samples from volunteers receiving T replacement therapies and excretion study samples were investigated.
Graphical abstract
We evaluated the safety and efficacy of fully closed-loop insulin therapy compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis. In an open-label, multinational, ...two-center, randomized crossover trial, 26 adults with type 2 diabetes requiring dialysis (17 men, 9 women, average age 68 ± 11 years (mean ± s.d.), diabetes duration of 20 ± 10 years) underwent two 20-day periods of unrestricted living, comparing the Cambridge fully closed-loop system using faster insulin aspart ('closed-loop') with standard insulin therapy and a masked continuous glucose monitor ('control') in random order. The primary endpoint was time in target glucose range (5.6-10.0 mmol l
). Thirteen participants received closed-loop first and thirteen received control therapy first. The proportion of time in target glucose range (5.6-10.0 mmol l
; primary endpoint) was 52.8 ± 12.5% with closed-loop versus 37.7 ± 20.5% with control; mean difference, 15.1 percentage points (95% CI 8.0-22.2; P < 0.001). Mean glucose was lower with closed-loop than control (10.1 ± 1.3 versus 11.6 ± 2.8 mmol l
; P = 0.003). Time in hypoglycemia (<3.9 mmol l
) was reduced with closed-loop versus control (median (IQR) 0.1 (0.0-0.4%) versus 0.2 (0.0-0.9%); P = 0.040). No severe hypoglycemia events occurred during the control period, whereas one severe hypoglycemic event occurred during the closed-loop period, but not during closed-loop operation. Fully closed-loop improved glucose control and reduced hypoglycemia compared with standard insulin therapy in adult outpatients with type 2 diabetes requiring dialysis. The trial registration number is NCT04025775.
and
are highly abundant human gut microbes in healthy individuals, and reduced levels are associated with inflammation and alterations of metabolic processes involved in the development of type 2 ...diabetes. Dietary factors can influence the abundance of
and
, but the evidence is not clear. We systematically searched PubMed and Embase to identify clinical trials investigating any dietary intervention in relation to
and
. Overall, 29 unique trials were included, of which five examined
19 examined
, and six examined both, in a total of 1444 participants. A caloric restriction diet and supplementation with pomegranate extract, resveratrol, polydextrose, yeast fermentate, sodium butyrate, and inulin increased the abundance of
, while a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols decreased the abundance of
. For
, the main studied intervention was prebiotics (e.g. fructo-oligosaccharides, inulin type fructans, raffinose); seven studies reported an increase after prebiotic intervention, while two studies reported a decrease, and four studies reported no difference. Current evidence suggests that some dietary factors may influence the abundance of
and
However, more research is needed to support these microflora strains as targets of microbiome shifts with dietary intervention and their use as medical nutrition therapy in prevention and management of chronic disease.
Blast-induced lung injury is associated with inflammatory, which are characterised by disruption of the alveolar-capillary barrier, haemorrhage, pulmonary infiltrateration causing oedema formation, ...pro-inflammatory cytokine and chemokine release, and anti-inflammatory counter-regulation. The objective of the current study was to define sequence of such alterations in with establishing blast-induced lung injury in rats using an advanced blast generator.
Rats underwent a standardized blast wave trauma and were euthanised at defined time points. Non-traumatised animals served as sham controls. Obtained samples from bronchoalveolar lavage fluid (BALF) at each time-point were assessed for histology, leukocyte infiltration and cytokine/chemokine profile.
After blast lung injury, significant haemorrhage and neutrophil infiltration were observed. Similarly, protein accumulation, lactate dehydrogenase activity (LDH), alveolar eicosanoid release, matrix metalloproteinase (MMP)-2 and -9, pro-Inflammatory cytokines, including tumour necrosis factor (TNF) and interleukin (IL) -6 raised up. While declining in the level of anti-inflammatory cytokine IL-10 occurred. Ultimately, pulmonary oedema developed that increased to its maximum level within the first 1.5 h, then recovered within 24 h.
Using a stablished model, can facilitate the study of inflammatory response to blast lung injury. Following the blast injury, alteration in cytokine/chemokine profile and activity of cells in the alveolar space occurs, which eventuates in alveolar epithelial barrier dysfunction and oedema formation. Most of these parameters exhibit time-dependent return to their basal status that is an indication to resilience of lungs to blast-induced lung injury.
Despite its well-established health benefits, exercise imposes challenges on glucose control in individuals with type 1 diabetes due to the complex interactions between exerciseinduced effects on ...glucose metabolism and exogenous insulin therapy. Although clinical guidelines for exercise management in type 1 diabetes are available, implementation is challenging in daily life. The risk of exercise-induced dysglycaemia deters many people with type 1 diabetes from participating and benefitting from exercise. Rapid progress has been made in the development of closed-loop systems, also known as the artificial pancreas. The autonomous modulation of insulin delivery in a glucoseresponsive manner by closed-loop systems may be beneficial in addressing and overcoming the risk and burden of exercise-induced dysglycaemia.
A summative overview of closed-loop application during exercise in type 1 diabetes is discussed, outlining current evidence and limitations, our perspectives in the field and future outlook.
Outcomes from clinical studies evaluating both single- and dual-hormone closed-loop during exercise are reported. Current approaches to enhance closed-loop performance during exercise are described.
Closed-loop system has the potential to ameliorate exercise management in type 1 diabetes. Promising results have been shown, however innovative approaches are still needed to overcome inherent limitations of closed-loop performance during exercise. Future studies in larger generalizable patient population during real-life settings are still needed, to further evaluate its clinical applicability.
Malnutrition is a common condition in hospitalized patients that is often underdiagnosed and undertreated. Hospital malnutrition has multifactorial causes and is associated with negative clinical and ...economic outcomes. There is now growing evidence from clinical trials for the efficiency and efficacy of nutritional support in the medical inpatient population. Since many medical inpatients at nutritional risk or malnourished are polymorbid (i.e., suffer from multiple comorbidities), this makes the provision of adequate nutritional support a challenging task, given that most of the clinical nutrition guidelines are dedicated to single diseases. This review summarizes the current level of evidence for nutritional support in not critically ill polymorbid medical inpatients.
The increasing importance to determine bioactive peptide hormones such as insulin, its synthetic analogs, and C-peptide in urine samples represents an analytical challenge. The physiological ...concentrations of insulin in urine are commonly found at sub-ng/mL levels and thus represent a complex analytical task. C-peptide concentrations, on the other hand, tend to be in the moderate ng/mL range and are hence much easier to determine. Insulin and C-peptide are important in the diagnostics and management of metabolic disorders such as diabetes mellitus and are also particularly relevant target analytes in professional sports and forensics. All insulins are classified on the World Anti-Doping Agency’s (WADA) list of prohibited substances and methods in sports with a minimum required performance level (MRPL) of 50 pg/mL. Until now, methods combining immunoextraction and subsequent mass spectrometric detection have mostly been used for this purpose. With the method developed here, sample preparation has been simplified considerably and does not require an antibody-based sample purification. This was achieved by a sophisticated mixed-mode solid-phase extraction and subsequent separation with liquid chromatography coupled to high-resolution mass spectrometry. Included target insulins were human, lispro, glulisine, aspart, glargine metabolite, degludec, and additionally, human C-peptide. The method was validated for the synthetic insulin analogs considering WADA requirements including specificity, limit of detection (10–25 pg/mL), limit of identification, recovery (25–100%), robustness, carry over (<2%), and matrix effects. All sample preparation steps were controlled by two stable isotope-labeled internal standards, namely, 2H10 LeuB6, B11, B15, B17-insulin and 13C6 Leu26, 30 C-peptide. Finally, the method was applied to samples from patients with diabetes mellitus treated with synthetic insulins.
Tight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve ...glucose control while alleviating the risk of hypoglycaemia in adults with HbA1c below 7·5% (58 mmol/mol).
In this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2–4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2–4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9–10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed.
Between March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6–13·4; p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% SD 8·1 when participants used usual pump therapy vs 76·2% 6·4 when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (53–74, p<0·0001) and below 2·8 mmol/L by 76% (59–86, p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred.
Use of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted.
Swiss National Science Foundation (P1BEP3_165297), JDRF, UK National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z).
Malnutrition is frequent in patients during a hospital admission and may further worsen during the hospital stay without appropriate nutritional support. Malnutrition causes greater complication ...rates, morbidity, and mortality rates, which increases the length of hospital stay and prolongs rehabilitation. Early recognition of individual nutritional risk and timely initiation of a tailored nutritional therapy are crucial. Recent evidence from large-scale trials suggests that efficient nutritional management not only improves the nutritional status, but also prevents negative clinical outcomes and increases patients' quality of life. Multifaceted clinical knowledge is required to ensure optimal nutritional support, according to a patient's individual situation and to avoid potential complications. Furthermore, clear definition of responsibilities and structuring of patient, and work processes are indispensable. Interdisciplinary and multiprofessional nutritional support teams have been built up to ensure and improve the quality and safety of nutritional treatments. These teams continuously check and optimize the quality of procedures in the core areas of nutritional management by implementing nutritional screening processes using a validated tool, nutritional status assessment, an adequate nutritional care plan development, prompt and targeted nutritional treatment delivery, and provision of accurate monitoring to oversee all aspects of care, from catering to artificial nutrition. The foundation of any nutritional care plan is the identification of patients at risk. The aim of this narrative review is to provide an overview about composition, tasks, and challenges of nutritional support teams, and to discuss the current evidence regarding their efficiency and efficacy in terms of clinical outcome and cost effectiveness.
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