Loss of incretin effect contributes to postprandial hyperglycaemia in cystic fibrosis-related diabetes.

AIM: To investigate the incretin axis in people with cystic fibrosis. METHODS: Adults with cystic fibrosis-related diabetes, cystic fibrosis without diabetes, and controls (adults without cystic fibrosis and without diabetes) underwent an oral glucose tolerance test and then a closely matched isoglycaemic i.v. glucose infusion. On each occasion, glucose, insulin, C-peptide, total and active glucagon-like peptide-1 and gastric inhibitory polypeptide responses were recorded and incremental areas under curves were calculated for 60 and 240 min. RESULTS: Five adults with cystic fibrosis-related diabetes, six with cystic fibrosis without diabetes and six controls, matched for age and BMI, completed the study. Glucose during oral glucose tolerance test closely matched those during isoglycaemic i.v. glucose infusion. The calculated incretin effect was similar in the control group and the cystic fibrosis without diabetes group (28% and 29%, respectively), but was lost in the cystic fibrosis-related diabetes group (cystic fibrosis-related diabetes vs control group: -6% vs 28%; p=0.03). No hyposecretion of glucagon-like peptide-1 or gastric inhibitory polypeptide was observed; conversely, 60-min incremental area under the curve for total glucagon-like peptide-1 was significantly higher in the cystic fibrosis-related diabetes group than in the control group [1070.4 (254.7) vs 694.97 (308.1); p=0.03] CONCLUSIONS: The incretin effect was lost in cystic fibrosis-related diabetes despite adequate secretion of the incretin hormones. These data support the concept that reduced incretin hormone insulinotropic activity contributes significantly to postprandial hyperglycaemia in cystic fibrosis-related diabetes.

ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted.

Managing an adult CF population in the COVID-19 pandemic-1 year on.

BACKGROUND: The advent of the COVID-19 pandemic in 2020 required an alteration in the routine care of people with CF (pwCF), deemed to be extremely vulnerable. AIM: We wished to report the alterations in clinical practice, including the introduction of remote video-assisted clinics, made to manage the adult pwCF attending our large centre. METHODS: We studied clinical records over a period of 2 years (March 2019 to February 2021) by comparing 19th March to 20th February (Y1) with 20th March to 21st February (Y2). RESULTS: We have shown out of hospital Multi Disciplinary Team (MDT) support increased and a greater proportion of IV therapy was administered at home. The VAC model of care increased clinical activity while reducing clinic non-attendance rates, suggesting more individuals engage with their carers. CONCLUSIONS: This new model of care has allowed greater engagement with pwCF.

Level-set segmentation of pulmonary nodules in megavolt electronic portal images using a CT prior.

PURPOSE: Pulmonary nodules present unique problems during radiation treatment due to nodule position uncertainty that is caused by respiration. The radiation field has to be enlarged to account for nodule motion during treatment. The purpose of this work is to provide a method of locating a pulmonary nodule in a megavolt portal image that can be used to reduce the internal target volume (ITV) during radiation therapy. A reduction in the ITV would result in a decrease in radiation toxicity to healthy tissue. METHODS: Eight patients with nonsmall cell lung cancer were used in this study. CT scans that include the pulmonary nodule were captured with a GE Healthcare LightSpeed RT 16 scanner. Megavolt portal images were acquired with a Varian Trilogy unit equipped with an AS1000 electronic portal imaging device. The nodule localization method uses grayscale morphological filtering and level-set segmentation with a prior. The treatment-time portion of the algorithm is implemented on a graphical processing unit. RESULTS: The method was retrospectively tested on eight cases that include a total of 151 megavolt portal image frames. The method reduced the nodule position uncertainty by an average of 40% for seven out of the eight cases. The treatment phase portion of the method has a subsecond execution time that makes it suitable for near-real-time nodule localization. CONCLUSIONS: A method was developed to localize a pulmonary nodule in a megavolt portal image. The method uses the characteristics of the nodule in a prior CT scan to enhance the nodule in the portal image and to identify the nodule region by level-set segmentation. In a retrospective study, the method reduced the nodule position uncertainty by an average of 40% for seven out of the eight cases studied.

Hyperconnectivity is a fundamental response to neurological disruption.

OBJECTIVE: In the cognitive and clinical neurosciences, the past decade has been marked by dramatic growth in a literature examining brain "connectivity" using noninvasive methods. We offer a critical review of the blood oxygen level dependent functional MRI (BOLD fMRI) literature examining neural connectivity changes in neurological disorders with focus on brain injury and dementia. The goal is to demonstrate that there are identifiable shifts in local and large-scale network connectivity that can be predicted by the degree of pathology. We anticipate that the most common network response to neurological insult is hyperconnectivity but that this response depends upon demand and resource availability. METHOD: To examine this hypothesis, we initially reviewed the results from 1,426 studies examining functional brain connectivity in individuals diagnosed with multiple sclerosis, traumatic brain injury, mild cognitive impairment, and Alzheimer's disease. Based upon inclusionary criteria, 126 studies were included for detailed analysis. RESULTS: RESULTS from 126 studies examining local and whole brain connectivity demonstrated increased connectivity in traumatic brain injury and multiple sclerosis. This finding is juxtaposed with findings in mild cognitive impairment and Alzheimer's disease where there is a shift to diminished connectivity as degeneration progresses. CONCLUSION: This summary of the functional imaging literature using fMRI methods reveals that hyperconnectivity is a common response to neurological disruption and that it may be differentially observable across brain regions. We discuss the factors contributing to both hyper- and hypoconnectivity results after neurological disruption and the implications these findings have for network plasticity.

Applying graphics processor units to Monte Carlo dose calculation in radiation therapy.

We investigate the potential in using of using a graphics processor unit (GPU) for Monte-Carlo (MC)-based radiation dose calculations. The percent depth dose (PDD) of photons in a medium with known absorption and scattering coefficients is computed using a MC simulation running on both a standard CPU and a GPU. We demonstrate that the GPU's capability for massive parallel processing provides a significant acceleration in the MC calculation, and offers a significant advantage for distributed stochastic simulations on a single computer. Harnessing this potential of GPUs will help in the early adoption of MC for routine planning in a clinical environment.

Effect of ultrasound probe on dose delivery during real-time ultrasound-guided tumor tracking.

Ultrasound is a noninvasive and less costly modality for real-time imaging of soft tissues. It has the capability of tracking soft tissue at levels of submillimeter precision even in the presence of radiation beams. The effect of a transducer on radiation dose is not fully known. The best imaging location for an ultrasound transducer happens to coincide with the path of an anterior-posterior beam in intensity modulated radiation therapy (IMRT). This study indicates a significant change in dose when this juxtaposition occurs. If the anterior-posterior beam is avoided in IMRT planning, however, the effect of the transducer on radiotherapy is found to be negligible.

Heart rate variability and baroreflex sensitivity are reduced in chronically undernourished, but otherwise healthy, human subjects.

Alterations in autonomic nerve activity in subjects in a chronically undernourished state have been proposed, but have been inadequately documented. The present study evaluated heart rate and systolic blood pressure variability in the frequency domain in two underweight groups, one of which was undernourished and recruited from the lower socio-economic strata [underweight, undernourished (UW/UN); n =15], while the other was from a high class of socio-economic background [underweight, well nourished (UW/WN); n =17], as well as in normal-weight controls [normal weight, well nourished (NW/WN); n =27]. Baroreflex sensitivity, which is a determinant of heart rate variability, was also assessed. The data indicate that total power (0-0.4 Hz), low-frequency power (0.04-0.15 Hz) and high-frequency power (0.15-0.4 Hz) of RR interval variability were significantly lower in the UW/UN subjects ( P <0.05) than in the NW/WN controls when expressed in absolute units, but not when the low- and high-frequency components were normalized for total power. Baroreflex sensitivity was similarly lower in the UW/UN group ( P <0.05). Heart rate variability parameters in the UW/WN group were generally between those of the UW/UN and NW/WN groups, but were not statistically different from either. The mechanisms that contribute to the observed differences between undernourished and normal-weight groups, and the implications of these differences, remain to be elucidated.