Dosimetric Risk Factors for Acute Radiation Pneumonitis in Patients With Prior Receipt of Immune Checkpoint Inhibitors

PurposeDosimetric parameters (e.g., mean lung dose (MLD), V20, and V5) can predict radiation pneumonitis (RP). Constraints thereof were formulated before the era of combined immune checkpoint inhibitors (ICIs) and radiotherapy, which could amplify the RP risk. Dosimetric predictors of acute RP (aRP) in the context of ICIs are urgently needed because no data exist thus far.Methods and MaterialsAll included patients underwent thoracic intensity-modulated radiotherapy, previously received ICIs, and followed-up at least once. Logistic regression models examined predictors of aRP (including a priori evaluation of MLD, V20, and V5), and their discriminative capacity was assessed by receiver operating characteristic analysis.ResultsMedian follow-up of the 40 patients was 5.3 months. Cancers were lung (80%) or esophageal (20%). ICIs were PD-1 (85%) or PD-L1 (15%) inhibitors (median 4 cycles). Patients underwent definitive (n=19), consolidative (n=14), or palliative (n=7) radiotherapy; the median equivalent dose in 2 Gy fractions (EQD2) was 60 Gy (IQR, 51.8-64 Gy). Grades 1-5 aRP occurred in 25%, 17.5%, 15%, 2.5%, and 5%, respectively. The only variables associated with any-grade aRP were V20 (p=0.014) and MLD (p=0.026), and only V20 with grade ≥2 aRP (p=0.035). Neither the number of prior ICI cycles nor the delivery of concurrent systemic therapy significantly associated with aRP risk. Graphs were constructed showing the incrementally increasing risk of aRP based on V20 and MLD (continuous variables).ConclusionsThis is the first study illustrating that V20 and MLD may impact aRP in the setting of prior ICIs. However, these data should not be extrapolated to patients without pre-radiotherapy receipt of prior ICIs, or to evaluate the risk of chronic pulmonary effects. If these results are validated by larger studies with more homogeneous populations, the commonly accepted V20/MLD dose constraints could require revision if utilized in the setting of ICIs.

E/E′ Is a New Independent Predictor of Recovered Ejection Fraction in Patients With Systolic Heart Failure Undergoing Ablation for Atrial Fibrillation

Aims: Catheter ablation should be considered in patients with atrial fibrillation (AF) and with heart failure (HF) with reduced ejection fraction (EF; HFrEF) to improve survival and reduce heart failure hospitalization. Careful patient selection for AF ablation is key to achieving similar outcome benefits. However, limited data exist regarding predictors of recovered ejection fraction. We aimed to evaluate the predictors of recovered ejection fraction in consecutive patients with HF undergoing AF ablation.Methods and Results: A total of 156 patients [67.3% men, median age 63 (11)] with AF and HF underwent initial catheter ablation between September 2017 and October 2019 in the First Affiliated Hospital of Dalian Medical University. Overall, the percentage of recovered ejection fractions was 72.3%. Recovered EFs were associated with a 39% reduction in all-cause hospitalization compared to non-recovered EFs at the 1-year follow-up [23.8 vs. 62.8 (odds ratio) OR 2.09 (1.40–3.12), P < 0.001]. Univariate analysis for recovered EFs showed that diabetes (P = 0.083), prevalent HF (P = 0.014), prevalent AF (P = 0.051), LVEF (P = 0.022), and E/E′ (P = 0.001) were associated with EF improvement. Multivariate analysis showed that the only independent predictor of EF recovery was E/E′ [OR 1.13 (1.03–1.24); P = 0.011]. A receiver operating characteristic analysis determined that the suitable cut-off value for E/E′ was 15 (sensitivity 38.7%, specificity 89.2%, the area under curve 0.704).Conclusions: Ejection fraction (EF) recovery occurred in 72.3% of patients, associated with a 39% reduction in all-cause hospitalization compared to the non-recovered EFs in our cohort. The only independent predictor of recovered EF was E/E′ < 15 in our series.

People with HIV Have Higher Risk of COVID-19 Diagnosis but Similar Outcomes than the General Population

Background We investigated the effect of HIV on COVID-19 outcomes with attention to selection bias due to differential testing and to comorbidity burden. Methods Retrospective cohort analysis using four hierarchical outcomes: positive SARS-CoV-2 test, COVID-19 hospitalization, intensive care unit (ICU) admission, and hospital mortality. The effect of HIV status was assessed using traditional covariate-adjusted, inverse probability weighted (IPW) analysis based on covariate distributions for testing bias (testing IPWs), HIV infection status (HIV IPWs), and combined models. Among PWH, we evaluated whether CD4 count and HIV plasma viral load (pVL) discriminated between those who did or did not develop study outcomes using receiver operating characteristic analysis. Results Between March and November 2020, 63,319 people were receiving primary care services at UCSD, of whom 4,017 were people living with HIV (PWH). PWH had 2.1 times the odds of a positive SARS-CoV-2 test compared to those without HIV after weighting for potential testing bias, comorbidity burden, and HIV-IPW (95% CI 1.6-2.8). Relative to persons without HIV, PWH did not have an increased rate of COVID-19 hospitalization after controlling for comorbidities and testing bias [adjusted incidence rate ratio (aIRR): 0.5, 95% CI: 0.1-1.4]. PWH had neither a different rate of ICU admission (aIRR:1.08, 95% CI; 0.31-3.80) nor in-hospital death (aIRR:0.92, 95% CI; 0.08-10.94) in any examined model. Neither CD4 count nor pVL predicted any of the hierarchical outcomes among PWH. Conclusions PWH have a higher risk of COVID-19 diagnosis but similar outcomes compared to those without HIV.

Rheological Investigation of Lipid Polymer Hybrid Nanocarriers for Oral Delivery of Felodipine (Conference Paper )#

The rheological behavior among factors that are present in Stokes law can be used to control the stability of the colloidal dispersion system. The felodipine lipid polymer hybrid nanocarriers (LPHNs) is an interesting colloidal dispersion system that is used for rheological characteristic analysis. The LPHNs compose of polymeric components and lipids. This research aims to prepare oral felodipine LPHNs to investigate the effect of independent variables on the rheological behavior of the nanosystem. The microwave-based technique was used to prepare felodipine LPHNs (H1-H9) successfully. All the formulations enter the characterization process for particle size and PDI to ascertain the colloidal properties of the prepared nanosystem then use coaxial rotational digital rheometer for rheological evaluation. The outcomes show that all felodipine LPHNs formulations (H1-H9) had a nanosize and homogenous structure that ascertain colloidal features of the nanodispersion system. The rheogram chart indicates that all of the felodipine LPHNs formulations (H1-H9) show pseudoplastic flow (non-Newtonian flow) that have shear-thinning property. The microwave-based method prepares felodipine LPHNs formulations (H1-H9) that show excellent physical texture that ascertains its ability as a technique for the preparation of nanoparticles. All of the felodipine LPHNs formulations (H1-H9) show pseudoplastic flow that supports the physical stability of the nanosystem.

Design and Analysis Considering Magnet Usage of Permanent Magnet Synchronous Generator Using Analytical Method

In this study, the characteristic analysis of a permanent magnet synchronous generator was performed using the analytical method, and the validity of the analytical method was compared with that of the finite element method (FEM). For the initial design, the rotor size was selected using the torque per rotor volume method, and the stator size was selected according to the saturation of the stator iron core. In addition, fast Fourier transform analysis was performed to determine the appropriate magnet thickness point, and it was confirmed that the open circuit and armature reaction magnetic flux densities were consistent with the FEM analysis results. Based on the analytical method, the generator circuit constants (phase resistance, back EMF, and inductance) were derived to construct an equivalent circuit. By applying the equivalent circuit method to the derived circuit constants, the accuracy of the equivalent circuit method was confirmed by comparing the FEM and experimental results.

Development of a Nomogram for Predicting the Occurrence of Symptomatic Intracranial Haemorrhage after Thrombectomy: A Single-Center Retrospective Observational Study

Background Symptomatic intracranial haemorrhage (SICH) is a severe and deadly complication in patients with large vessel occlusion (LVO) who receive endovascular treatment (EVT). Recent studies have indicated that many risk factors, including pretreatment scores and the operation process, may be associated with the occurrence of SICH after thrombectomy. This study aims to identify independent risk factors and establish a novel nomogram-based model for patients with anterior LVO to predict the occurrence of SICH after direct thrombectomy or bridge therapy (thrombectomy based on intravenous thrombolysis). Methods Patients with acute ischaemic stroke after EVT to recanalize the blocked artery in anterior circulation were consecutively recruited from November 2017 to March 2019. Baseline information was collected from each patient. These data were subsequently analysed by R Project for Statistical Computing. Results A total of 127 patients with complete data were classified into the training set, among whom 37 patients (29.1%) fulfilled the criteria for SICH. The results of the multivariate analyses showed that NIHSS (P=0.024), ASPECT (P<0.001) and ASITN (P=0.017) scores were independently associated with the occurrence of SICH after thrombectomy. Ultimately, three independent pretreatment predictors were included in the NIHSS/ASPECT/ASITN (NAA) prediction model, and the receiver operating characteristic analysis results showed an area under the curve (AUC) of 0.845 (95% CI=0.763–0.928). The calibration plots showed that the actual observations were consistent with the measured and predicted results of the nomogram. Conclusions In this study, a novel model based on NAA for predicting the occurrence of SICH after thrombectomy in patients with anterior LVO was established and validated internally. The results suggest that this model can help improve perioperative evaluations and individualized treatment strategies.

Identification and Evolutionary Characteristic Analysis of STARD Gene Family, and Overexpression VvSTARD5 Responses to Salt Stress in Tomato

This study aimed to have a full understanding of the steroidogenic acute regulatory gene family member and evolutionary relationship in grape. 23 VvSTARD gene members were identified and divided into five groups in different species. Analyses of the gene codon preference, selective pressure, and tandem duplication of the VvSTARD, AtSTARD, and OsSTARD genes indicated that synteny relationship occurred in grapes, Arabidopsis thaliana, and rice genomes. The 8 lipid transporter proteins were found in the tertiary structure of the STARD gene family in grape. Expression profiles of the three species microarrays showed that the expression levels of the STARD genes in different organs and the response to abiotic stress in the same subgroup had similar characteristics. In addition, analysis of the VvSTARD genes expression levels was detected in response to different hormones and abiotic stresses by quantitative real-time polymerase chain reaction (qRT-PCR), and the results were the same as those predicted by the cis-elements and the expression profiles. Meanwhile, VvSTARD5 gene was screened in high concentration NaCl treatment by qRT-PCR. Furthermore, the VvSTARD5 was located at the nucleus by subcellular location. Through the function analysis of salt tolerance in transgenic tomato, overexpression VvSTARD5 obviously improved tolerance to salt stress. Taken together, our findings Preliminary identify the functions of VvSTARD gene family and vertify STARD5 that be likely involved in regulating salt tolerance, which may have potential application molecular breeding in grape.