Background and Purpose: Hypertensive disorders of pregnancy (HDP) comprise 4 subtypes. Previous studies have not investigated the relationship between stroke risk, different HDP subtypes, and follow-up time, which was the purpose of this study. Methods: Data of 17 588 women aged 18 to 45 years who had a history of HDP in Taiwan from 2000 to 2017 was retrospectively reviewed. After matching with confounders, 13 617 HDP women and 54 468 non-HDP women were recruited. Results: HDP women had an adjusted hazard ratio (aHR) of 1.71 (95% CI, 1.46−2.00) for stroke, and 1.60 (1.35−1.89) and 2.98 (2.13−4.18) for ischemic and hemorrhagic stroke, respectively ( P <0.001 for all). The overall stroke risk in the HDP group was still 2.04 times 10 to 15 years after childbirth (1.47−2.83, P <0.001). Although the risks of both ischemic and hemorrhagic stroke persisted, their risk time trends were different. The risk of ischemic stroke reached peak during 1 to 3 years after childbirth with an aHR of 2.14 (1.36–3.38), while hemorrhagic stroke risk gradually increased and had an aHR of 4.64 (2.47−8.73) after 10 to 15 years of childbirth (both P <0.001). Among the 4 HDP subtypes, chronic hypertension with superimposed preeclampsia had the highest stroke risk (aHR=3.86, 1.91−7.82, P <0.001), followed by preeclampsia–eclampsia (aHR=2.00, 1.63−2.45, P <0.001), and gestational hypertension (aHR=1.68, 1.13−2.52, P 0.05). Furthermore, multiple HDP combined with preeclampsia had aHR of 5.48 (1.14−26.42, P <0.05). Conclusions: The effect of HDP on the risk of future stroke persisted for up to 17 years, both for ischemic and hemorrhagic strokes. The presence of multiple HDP and preeclampsia further increase the stroke risk.
Background and purposes: The long-term risk of stroke in women with preeclampsia/eclampsia is a concerning issue. In this study we further investigated different stroke subtypes and differentiated follow-up time intervals. Methods: Between 2000 and 2017, 1,384,427 pregnant women were registered in the National Health Insurance Research Database in Taiwan. After excluding women with previous stroke history and exact matching with all confounders, 6,053 women with preeclampsia/eclampsia and 24,212 controls were included in the analysis sample. Results: Over the 17-year follow-up, the adjusted hazard ratio (aHR) for stroke in women with preeclampsia/eclampsia was 2.05 (95% confidence interval, CI = 1.67–2.52, p<0.001). The 17 years overall aHR of both ischemic and hemorrhagic stroke were 1.98 and 3.45, respectively (p<0.001). The stroke subtypes, hemorrhagic and ischemic, had different time trend risks, and hemorrhagic stroke risks kept higher than that of ischemic stroke. The aHR of ischemic stroke reached a peak during 1–3 years after childbirth (aHR = 3.09). The aHR of hemorrhagic stroke reached a peak during 3–5 years (aHR = 7.49). Conclusions: Stroke risk persisted even after decades, for both ischemic and hemorrhagic subtypes. Women with preeclampsia/eclampsia history should be aware of the long-term risk of stroke.
Gene Ontology (GO) analysis can provide a comprehensive function analysis for investigating genes, allowing us to identify the potential biological roles of genes. The present study conducted GO analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in disease progression and mediating tumor response to RT. Methods: We performed a GO enrichment analysis on the RNA-seq data to validate radiation-induced gene expression. A total of 172 I-IVB specimens from oral squamous cell carcinoma patients were collected for clinical analysis, from which IRAK2 expression was analyzed by immunohistochemistry. This was a retrospective study conducted between IRAK2 expression and the outcomes of oral squamous cell carcinoma patients after radiotherapy treatment. We conducted Gene Ontology (GO) analysis to explore the biological function of IRAK2 and performed a case analysis to define its clinical role in mediating tumor response to radiotherapy. GO enrichment analysis to validate radiation-induced gene expression was performed. Clinically, 172 stage I-IVB resected oral cancer patients were used to validate IRAK2 expression in predicting clinical outcomes. GO enrichment analysis showed that IRAK2 is involved in 10 of the 14 most enriched GO categories for post-irradiation biological processes, focusing on stress response and immune modulation. Clinically, high IRAK2 expression was correlated with adverse disease features, including pT3-4 status (p = 0.01), advanced overall stage (p = 0.02), and positive bone invasion (p = 0.01). In patients who underwent radiotherapy, the IRAK2-high group was associated with reduced post-irradiation local recurrence (p = 0.025) compared to the IRAK2-low group. IRAK2 plays a crucial role in the radiation-induced response. Patients with high IRAK2 expression demonstrated more advanced disease features but predicted higher post-irradiation local control in a clinical setting. These findings support IRAK2 as a potential predictive biomarker for radiotherapy response in non-metastatic and resected oral cancer patients.
Radioliposomes have potential applications as theranostic nanoparticles. Several techniques have been developed to label liposomes with radionuclides. Methods: In this study, a new In-111 surface labeling method for 1,4,7,10-tetraazacyclododecane-N, N', N", N'"-tetraacetic acid (DOTA) derivative liposomes (DLs) is described. The in vitro stability and in vivo molecular imaging properties of the labeled liposomes were compared with those of conventional 111 In-liposomes ( 111 In-Ls) prepared by a remote loading method. In vitro stability tests were performed in normal saline, rat plasma, and human plasma at 37°C. Imaging characteristics of both radioliposomal preparations were determined in LS174T tumor-bearing mice. Results: The labeling efficiency of In-111-labeled DL ( 111 In-DLs) was greater than 95%; accordingly, no post-labeling purification was required, in contrast to the 111 In-Ls. The specificity of 111 In-DLs was higher (>10 111 In per liposome) than that of 111 In-Ls (<;2 111 In per liposome). The two radioliposomes showed similar in vitro stability. Non-invasive longitudinal monitoring by micro-single-photon emission computed tomography/computed tomography showed a similar in vivo tumor distribution for the two radioliposomes (48 h post-injection, P > 0.05). Conclusion: The new 111 In surface labeling method for liposomes was rapid, efficient, highly specific activity, and easy to perform. Although the two radioliposomes showed similar in vitro and in vivo characteristics, 111 In-DLs have benefits for clinical drug preparation, and this surface labeling method is a promising platform for radioliposomal theranostic nanoparticle preparation.
Purpose: Pulmonary function analysis is essential for implementing functional avoidance in modern radiotherapy treatment planning. The gold standard for pulmonary function analysis is the SPECT V-Q scan. However, additional radiation exposure introduced and dynamic image fusion remains obstacles in treatment planning. Methods and Materials: This study proposes a hybrid deformable image registration method for pulmonary ventilation functional analysis. The proposed method separates the deformation of the human lung into two parts, deformation of the outer boundaries and the inner lung tissue. In reality, the deformation of the lung boundaries is constrained by adjacent organs such as the heart, parietal pleura, and diaphragm, where the lung boundaries exhibit non-linear, anisotropic deformation behavior, especially near the diaphragm; the inner lung tissue exhibit a more fluid-like, viscous deformation behavior. Therefore, in this study, the lung boundaries are modeled using the coherent point drift (CPD) registration method, while the inner lung tissue is registered using the Demons registration method. The proposed hybrid DIR method establishes the correspondence between exhalation and inhalation 3D-CT images of a 4D-CT data set. Finally, a ventilation functional map is then constructed based on the difference in Hounsfield Units (HU) and compared to the ventilation of SPECT. Results: For all 4D-CT SPECT data sets, the ventilation of the corresponding functional maps was found to deviate by no more than 7.92%. In addition, the lowest correlation between the corresponding functional maps is found to be 0.68, and the highest is 0.87. Conclusion: With the results of this study, the basic feasibility of the proposed DIR for pulmonary functional analysis is confirmed. Furthermore, the 4D-CT-based ventilation functional maps have higher resolution compared to SPECT ventilation maps and give evidence of the former as a replacement for the latter.