ABSTRACT
BACKGROUND: The clinical utility of radiomics is hampered by a high correlation between the large number of features analysed which may result in the "bouncing beta" phenomenon which could in part explain why in a similar patient population texture features identified and/or cut-off values of prognostic significance differ from one study to another. Principal component analysis (PCA) is a technique for reducing the dimensionality of large datasets containing highly correlated variables, such as texture feature datasets derived from FDG PET images, increasing data interpretability whilst at the same time minimizing information loss by creating new uncorrelated variables that successively maximize variance. Here, we report on PCA of a texture feature dataset derived from 123 malignant melanoma lesions with a significant range in lesion size using the freely available LIFEx software. RESULTS: Thirty-eight features were derived from all lesions. All features were standardized. The statistical assumptions for carrying out PCA analysis were met. Seven principal components with an eigenvalue > 1 were identified. Based on the "elbow sign" of the Scree plot, only the first five were retained. The contribution to the total variance of these components derived using Varimax rotation was, respectively, 30.6%, 23.6%, 16.1%, 7.4% and 4.1%. The components provided summarized information on the locoregional FDG distribution with an emphasis on high FDG uptake regions, contrast in FDG uptake values (steepness), tumour volume, locoregional FDG distribution with an emphasis on low FDG uptake regions and on the rapidity of changes in SUV intensity between different regions. CONCLUSIONS: PCA allowed to reduce the dataset of 38 features to a set of 5 uncorrelated new variables explaining approximately 82% of the total variance contained within the dataset. These principal components may prove more useful for multiple regression analysis considering the relatively low numbers of patients usually included in clinical trials on FDG PET texture analysis. Studies assessing the superior differential diagnostic, predictive or prognostic value of principal components derived using PCA as opposed to the initial texture features in clinical relevant settings are warranted.
ABSTRACT
The COVID-19 pandemic has disrupted life throughout the world. Newly developed vaccines promise relief to people who live in high-income countries, although vaccines and expensive new treatments are unlikely to arrive in time to help people who live in low-and middle-income countries. The pathogenesis of COVID-19 is characterized by endothelial dysfunction. Several widely available drugs like statins, ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have immunometabolic activities that (among other things) maintain or restore endothelial cell function. For this reason, we undertook an observational study in four Belgian hospitals to determine whether in-hospital treatment with these drugs could improve survival in 959 COVID-19 patients. We found that treatment with statins and ACEIs/ARBs reduced 28-day mortality in hospitalized COVID-19 patients. Moreover, combination treatment with these drugs resulted in a 3-fold reduction in the odds of hospital mortality (OR=0.33; 95% CI 0.17-0.69). These findings were in general agreement with other published studies. Additional observational studies and clinical trials are needed to convincingly show that in-hospital treatment with statins, ACEIs/ARBs, and especially their combination saves lives.
ABSTRACT
Rising population density and global mobility are among the reasons why pathogens such as SARS-CoV-2, the virus that causes COVID-19, spread so rapidly across the globe. The policy response to such pandemics will always have to include accurate monitoring of the spread, as this provides one of the few alternatives to total lockdown. However, COVID-19 diagnosis is currently performed almost exclusively by Reverse Transcription Polymerase Chain Reaction (RT-PCR). Although this is efficient, automatable and acceptably cheap, reliance on one type of technology comes with serious caveats, as illustrated by recurring reagent and test shortages. We therefore developed an alternative diagnostic test that detects proteolytically digested SARS-CoV-2 proteins using Mass Spectrometry (MS). We established the Cov-MS consortium, consisting of fifteen academic labs and several industrial partners to increase applicability, accessibility, sensitivity and robustness of this kind of SARS-CoV-2 detection. This in turn gave rise to the Cov-MS Digital Incubator that allows other labs to join the effort, navigate and share their optimizations, and translate the assay into their clinic. As this test relies on viral proteins instead of RNA, it provides an orthogonal and complementary approach to RT-PCR, using other reagents that are relatively inexpensive and widely available, as well as orthogonally skilled personnel and different instruments. Data are available via ProteomeXchange with identifier PXD022550.
ABSTRACT
Background.COVID-19 infection has limited preventive or therapeutic drug options at this stage. Some of common existing drugs like angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and the HMG-CoA reductase inhibitors ( statins) have been hypothesised to impact on disease severity. However, up till now, no studies investigating this association were conducted in the most vulnerable and affected population groups, i.e. older people residing in nursing homes. The purpose of this study has been to explore the association of ACEi/ARB and/or statins with clinical manifestations in COVID-19 infected older people residing in nursing homes. Methods and Findings.We undertook a retrospective multi-centre cohort study in two Belgian nursing homes that experienced similar COVID-19 outbreaks. COVID-19 diagnoses were based on clinical suspicion and/or viral presence using PCR of nasopharyngeal samples. A total of 154 COVID-19 positive subjects was identified. The outcomes were 1) serious COVID-19 defined as a long-stay hospital admission (length of stay [≥] 7 days) or death (at hospital or nursing home) within 14 days of disease onset, and 2) asymptomatic, i.e. no disease symptoms in the whole study-period while still being PCR diagnosed. Disease symptoms were defined as any COVID-19-related clinical symptom (e.g. coughing, dyspnoea, sore throat) or sign (low oxygen saturation and fever) for [≥] 2 days out of 3 consecutive days. Logistic regression models with Firth corrections were applied on these 154 subjects to analyse the association between ACEi/ARB and/or statin use with the outcomes. Age, sex, functional status, diabetes and hypertension were used as covariates. Sensitivity analyses were conducted to evaluate the robustness of our statistical significant findings. We found a statistically significant association between statin intake and the absence of symptoms during COVID-19 infection (unadjusted OR 2.91; CI 1.27-6.71; p=0.011), which remained statistically significant after adjusting for age, sex, functional status, diabetes mellitus and hypertension. The strength of this association was considerable and clinically important. Although the effects of statin intake on serious clinical outcome (long-stay hospitalisation or death) were in the same beneficial direction, these were not statistically significant (OR 0.75; CI 0.25-1.85; p=0.556). There was also no statistically significant association between ACEi/ARB and asymptomatic status (OR 1.52; CI 0.62-3.50; p=0.339) or serious clinical outcome (OR 0.79; CI 0.26-1.95; p=0.629). Conclusions.Our data indicate that statin intake in old, frail people could be associated with a considerable beneficial effect on COVID-19 related clinical symptoms. The role of statins and any interaction with renin-angiotensin system drugs need to be further explored in larger observational studies as well as randomised clinical trials.
ABSTRACT
Obestatin is a ghrelin-associated peptide hormone with presumed anorexigenic and inhibitory effect on gastric propulsive motility activity. Recent literature, however, discloses much contestation over satiety and gastrointestinal motility-related functionalities of obestatin. In addition, antidipsinogenic effects in rodents by obestatin were recently reported. The present study was set up to bring more clarity into the contested effects of obestatin on food and water intake. Additionally, the stability of obestatin in brain tissue homogenate was investigated. The in vitro incubation of obestatin in brain homogenates revealed disappearance half-life times of 19 min for crude brain homogenate to 27 min for brain membrane homogenate. For the behavioural studies, male C57Bl/6 mice were intracerebroventricularly treated with 0.2 nmol murine amidated obestatin or vehicle at the age of 3 months. An additional group of mice was treated with 0.3 nmol of corticotropin releasing factor (CRF) as a positive control of suppression of food intake. Food and water intake were studied over a period of 5 h in metabolic cages. Under our experimental conditions, no suppressive effects of obestatin on food or water intake were observed, whereas CRF evoked a significant suppression of food intake, which proves the internal validity of the study design.
