Exploring Response to Immunotherapy in Non-Small Cell Lung Cancer Using Delta-Radiomics

Delta-radiomics is a branch of radiomics in which features are confronted after time or after introducing an external factor (such as treatment with chemotherapy or radiotherapy) to extrapolate prognostic data or to monitor a certain condition. Immune checkpoint inhibitors (ICIs) are currently revolutionizing the treatment of non-small cell lung cancer (NSCLC); however, there are still many issues in defining the response to therapy. Contrast-enhanced CT scans of 33 NSCLC patients treated with ICIs were analyzed; altogether, 43 lung lesions were considered. The radiomic features of the lung lesions were extracted from CT scans at baseline and at first reassessment, and their variation (delta, Δ) was calculated by means of the absolute difference and relative reduction. This variation was related to the final response of each lesion to evaluate the predictive ability of the variation itself. Twenty-seven delta features have been identified that are able to discriminate radiologic response to ICIs with statistically significant accuracy. Furthermore, the variation of nine features significantly correlates with pseudo-progression.

A Systematic Review and Meta-Analysis of the Effectiveness of Neuroprotectants for Paclitaxel-Induced Peripheral Neuropathy

BackgroundPaclitaxel-induced peripheral neuropathy (PIPN) is a disabling side effect of paclitaxel with few effective preventive strategies. We aim to determine the efficacy of pharmacological and non-pharmacological neuroprotective interventions in preventing PIPN incidence.MethodsBiomedical literature databases were searched from years 2000 to 2021 for trials comparing neuroprotective interventions and control. Meta-analysis was performed using the random-effects model. The primary outcome was the incidence of PIPN.ResultsOf 24 relevant controlled trials, 14 were eligible for meta-analysis. Pooled results from seven non-pharmacological trials were associated with a statistically significant 48% relative reduction of PIPN risk with low heterogeneity. Conversely, pooled results from six pharmacological trials were associated with a significant 20% relative reduction of PIPN risk with moderate heterogeneity. Both pharmacological and non-pharmacological approaches appear effective in reducing PIPN incidence in the treatment arm compared to control (pooled RR < 1).ConclusionCurrent evidence suggests that both interventions may reduce PIPN risk. Non-pharmacological interventions appear more effective than pharmacological interventions.

Using Belgian pharmacy dispensing data to assess antibiotic use for children in ambulatory care

Background The desired effect of antibiotics is compromised by the rapid escalation of antimicrobial resistance. Children are particularly at high-risk for unnecessary antibiotic prescribing, which is owing to clinicians’ diagnostic uncertainty combined with parents’ concerns and expectations. Recent Belgian data on ambulatory antibiotic prescribing practices for children are currently lacking. Therefore, we aim to analyse different aspects of antibiotic prescriptions for children in ambulatory care. Methods Pharmacy dispensing data on antibiotics for systematic use referring from 2010 to 2019 were retrieved from Farmanet, a database of pharmaceutical dispensations in community pharmacies. Population data were obtained from the Belgian statistical office (Statbel). Descriptive statistics were performed in Microsoft Excel. The Mann-Kendall test for trend analysis and the seasplot function for seasonality testing were conducted in R. Results The past decade, paediatric antibiotic use and expenditures have relatively decreased in Belgian ambulatory care with 35.5% and 44.3%, respectively. The highest volumes of antibiotics for children are prescribed by GPs working in Walloon region and rural areas, to younger children, and during winter. The most prescribed class of antibiotics for children are the penicillins and the biggest relative reduction in number of packages is seen for the sulfonamides and trimethoprim and quinolone antibacterials. Conclusions Paediatric antibiotic use has decreased in Belgian ambulatory care. Further initiatives are needed to promote prudent antibiotic prescribing in ambulatory care.

Intravenous Thrombolysis After First-Ever Ischemic Stroke and Reduced Incident Dementia Rate

Background and Purpose: The use of intravenous thrombolysis is associated with improved clinical outcomes. Whether thrombolysis is associated with reduced incidence of poststroke dementia remains uncertain. We sought to estimate if the use of thrombolysis following first-ever ischemic stroke was associated with a reduced rate of incident dementia using a pragmatic observational design. Methods: We included first-ever ischemic stroke patients from the Ontario Stroke Registry who had not previously been diagnosed with dementia. The primary outcome was incident dementia ascertained by a validated diagnostic algorithm. We employed inverse probability of treatment-weighted Cox proportional hazard models to estimate the cause-specific hazard ratio for the association of thrombolysis and incident dementia at 1 and 5 years following stroke. Results: From July 2003 to March 2013, 7072 patients with ischemic stroke were included, 3276 (46.3%) were female and mean age was 71.0 (SD, 12.8) years. Overall, 38.2% of the cohort (n=2705) received thrombolysis, 77.2% (n=2087) of which was administered within 3 hours of stroke onset. In the first year following stroke, thrombolysis administration was associated with a 24% relative reduction in the rate of developing dementia (cause-specific hazard ratio, 0.76 [95% CI, 0.58–0.97]). This association remained significant at 5 years (cause-specific hazard ratio, 0.79 [95% CI, 0.66–0.91]) and at the end of follow-up (median 6.3 years; cause-specific hazard ratio, 0.79 [95% CI, 0.68–0.89]). Conclusions: Thrombolysis administration following first-ever ischemic stroke was independently associated with a reduced rate of dementia. Incident dementia should be considered as a relevant outcome when evaluating risk/benefit of thrombolysis in ischemic stroke patients.

How the COVID-19 pandemic changed postoperative infections in urology wards: A retrospective cohort study from two urology departments

Introduction: We aimed to compare the rate of postoperative infection and drug-resistant organism (DRO) before and during the COVID-19 pandemic in urology departments. Methods: A retrospective cohort study was carried out. Data from all elective surgical procedures carried out in two urology departments between April and June 2018 and the homologous period in 2020 were collected. Main outcomes were the number of postoperative infections during the pandemic, and the number of DROs. Sample size was calculated based on a 50% relative reduction of infections during the pandemic. Variables were compared by Chi-squared test, and multivariable logistic regression was used to estimate predictors. Results: A total of 698 patients undergoing elective surgery were included. The postoperative infection rate during the pre-pandemic period was of 14.1% compared to 12.1% during the pandemic (p=0.494). DROs were lower during the pandemic (92.3% vs. 52.4%, p=0.002). The pandemic period was the main predictor for reduced multi-drug-resistant isolates, with an odds ratio of 0.10 (p=0.010, 95% confidence interval 0.016–0.57). Conclusions: Postoperative infection rates were not significantly reduced during the COVID-19 pandemic, despite the adoption of enhanced infection preventive measures. There was, however, a decrease in the rate of DROs during this period, suggesting a secondary benefit to enhanced infection prevention practices adopted during the COVID-19 era.

Glacier Area and Snow Cover Changes in the Range System Surrounding Tarim from 2000 to 2020 Using Google Earth Engine

Glacier and snow are sensitive indicators of regional climate variability. In the early 21st century, glaciers in the West Kunlun and Pamir regions showed stable or even slightly positive mass budgets, and this is anomalous in a worldwide context of glacier recession. We studied the evolution of snow cover to understand whether it could explain the evolution of glacier area. In this study, we used the thresholding of the NDSI (Normalized Difference Snow Index) retrieved with MODIS data to extract annual glacier area and snow cover. We evaluated how the glacier trends related to snow cover area in five subregions in the Tarim Basin. The uncertainty in our retrievals was assessed by comparing MODIS results with the Landsat-5 TM in 2000 and Landsat-8 OLI in 2020 glacier delineation in five subregions. The glacier area in the Tarim Basin decreased by 1.32%/a during 2000–2020. The fastest reductions were in the East Tien Shan region, while the slowest relative reduction rate was observed in the West Tien Shan and Pamir, i.e., 0.69%/a and 1.08%/a, respectively, during 2000–2020. The relative glacier stability in Pamir may be related to the westerlies weather system, which dominates climate in this region. We studied the temporal variability of snow cover on different temporal scales. The analysis of the monthly snow cover showed that permanent snow can be reliably delineated in the months from July to September. During the summer months, the sequence of multiple snowfall and snowmelt events leads to intermittent snow cover, which was the key feature applied to discriminate snow and glacier.

Influence of Peripheral Transluminal Angioplasty Alongside Exercise Training on Oxidative Stress and Inflammation in Patients with Peripheral Arterial Disease

In patients with intermittent claudication, exercise training ameliorates inflammation by reducing oxidative stress. A total of 41 patients with intermittent claudication (Rutherford 3) were included in the study (with 21 patients treated by endovascular revascularization (ER), and 20 patients without ER). All patients were referred to home-based exercise training. Absolute and initial claudication distance (ACD, ICD) and ABI (ankle–brachial index) were measured. ROS (reactive oxygen species) formation was measured using the luminol analogue L-012. Follow-up was performed after 3 months. ROS production after NOX2 (NAPDH oxidase 2) stimulation showed a significant reduction in both groups at follow-up (PTA group: p = 0.002, control group: p = 0.019), with a higher relative reduction in ROS in the PTA group than in the control group (p = 0.014). ABI measurements showed a significant increase in the PTA (peripheral transluminal angioplasty) group (p = 0.001), but not in the control group (p = 0.127). Comparing both groups at follow-up, ABI was higher in the PTA group (p = 0.047). Both groups showed a significant increas ACD and ICD at follow-up (PTA group: ACD: p = 0.001, ICD: p < 0.0001; control group: ACD: p = 0.041, ICD: p = 0.002). There was no significant difference between both groups at follow-up (ACD: p = 0.421, ICD: p = 0.839). Endovascular therapy in combination with exercise training leads to a lower leukocyte activation state with a reduced NOX2-derived ROS production paralleled by an improved ABI, ACD and ICD. Our data support the strategy to combine exercise training with preceding endovascular therapy.

Risk Management Assessment Improves the Cost-Effectiveness of Invasive Species Prioritisation

International agreements commit nations to control or eradicate invasive alien species. The scale of this challenge exceeds available resources and so it is essential to prioritise the management of invasive alien species. Species prioritisation for management typically involves a hierarchy of processes that consider the likelihood and scale of impact (risk assessment) and the feasibility, costs and effectiveness of management (risk management). Risk assessment processes are widely used, risk management less so, but are a crucial component of resource decision making. To assess the cost-effectiveness of prioritisation, we considered 26 high-risk species considered for eradication from Great Britain (GB) with pre-existing risk assessment and risk management outputs. We extracted scores to reflect the overall risk to GB posed by the species, together with the estimated cost and the overall feasibility of eradication. We used these to consider the relative reduction in risk per unit cost when managing prioritised species based on different criteria. We showed that the cost-effectiveness of prioritisation within our sample using risk assessment scores alone, performed no better than a random ranking of the species. In contrast, prioritisation including management feasibility produced nearly two orders of magnitude improvement compared to random. We conclude that basing management actions on priorities based solely on risk assessment without considering management feasibility risks the inefficient use of limited resources. In this study, the cost-effectiveness of species prioritisation for action was greatly increased by the inclusion of risk management assessment.

Praziquantel Treatment of Schistosoma mansoni Infected Mice Renders Them Less Susceptible to Reinfection

Beyond transient control of the infection, additional benefits of mass drug administration of praziquantel in endemic communities have been suggested in communities but not mechanistically investigated experimentally. The present study sought to evaluate the additional and hitherto unreported benefits of repeated mass drug administration of praziquantel. We used a tractable mouse model of Schistosoma mansoni infection to assess the effects of repeated infection-treatment cycles on the host susceptibility to reinfection. Parasitaemia was assessed by quantification of Schistosoma egg burden in liver tissues and morbidity was followed up by histological observation of liver lesions by microscopy and using biochemical measurement of liver transaminases. Immune responses were further determined by serum probing of schistosoma-specific antibodies, cytokines and quantification of liver cellular and soluble mediator responses by flow cytometry and ELISA, respectively. At similar ages and comparable gender distribution, groups of mice undergoing higher number of infections treatment cycles over a longer period, remained susceptible to reinfection by the parasite, as judged by the presence of eggs and the associated increasing pathology in the liver tissues. However, notably, there was a clear and significantly higher propensity to lower egg burden upon reinfection when compared to counterparts undergoing a lower number of infection-treatment cycles. This relative reduction of susceptibility to infection was paralleled by a more robust humoral response against parasite antigens, elevated serum IL-4 and liver cytokines. Of note, praziquantel treatment of infected mice left them at a higher baseline of serum IL-4, IgE and liver cytokines but lower CD4+ T cell -derived cytokines when compared to infected non-treated mice supporting an immunological treatment-induced advantage of previously infected mice over naïve mice and infected/not treated mice. Notably, repeated infection-treatment cycles did not preclude the infection-driven aggravation of collagen deposition in the livers over time and was corroborated by a more robust local production of inflammatory cytokines in the most exposed livers. Taken together, our data reveal that treatment of S. mansoni-infected hosts with praziquantel rewires the immune system to a conformation less permissive to subsequent reinfection in mice. Provided the data are translatable from mouse to human, our findings may provide mechanistic support to the potential benefits of more frequent MDAs in high transmission areas to allow rapid acquisition of protective immunity against reinfection.

Multi-Input Convolutional Neural Networks for Automatic Pollen Classification

Pollen allergies are a cause of much suffering for an increasing number of individuals. Current pollen monitoring techniques are lacking due to their reliance on manual counting and classification of pollen by human technicians. In this study, we present a neural network architecture capable of distinguishing pollen species using data from an automated particle measurement device. This work presents an improvement over the current state of the art in the task of automated pollen classification, using fluorescence spectrum data of aerosol particles. We obtained a relative reduction in the error rate of over 48%, from 27% to 14%, for one of the datasets, with similar improvements for the other analyzed datasets. We also use a novel approach for doing hyperparameter tuning for multiple input networks.