Background
In this exploratory analysis from the PRODIGY study, we aimed to define the radiological criteria to identify patients with gastric cancer who may derive maximal clinical benefit from ...neoadjuvant chemotherapy.
Patients and methods
There were 246 patients allocated to receive surgery followed by adjuvant S-1 (SC group) and 238 allocated to receive neoadjuvant chemotherapy (CSC group). As the PRODIGY’s radiological method of lymph node (LN) evaluation considers short diameter and morphology (the size and morphology method), a method considering only short diameter was also employed. In the SC group, the correlation between radiologic and pathologic findings was analyzed. The hazard ratio (HR) for the progression-free survival (PFS) of the CSC group was analyzed in subgroups with different cT/N stages.
Results
cT4 disease showed a sensitivity of 85.6% for detecting pT4 and had a low proportion of pathologic stage (pStage) I disease (4.5%). Among the criteria determined by different cT/N stages by each method of LN positivity, those involving cT4Nany or cT4N + by both methods had a minimal proportion of pStage I disease (≤ 5%), while cT4Nany by both methods and cT4N + by the size and morphology method exhibited ≥ 75.9% sensitivity for detecting pStage III disease. The relative risk reduction in PFS of the CSC group was greatest in patients meeting the cT4Nany criterion defined by both methods (HR 0.67, 95% confidence interval 0.48–0.93).
Conclusions
The cT4Nany criterion, regardless of the radiological method used for LN evaluation, may help select patients with resectable gastric cancer for neoadjuvant chemotherapy.
Despite being the gold standard for diagnosis of osteoporosis, dual-energy X-ray absorptiometry (DXA) could not be widely used as a screening tool for osteoporosis. This study aimed to predict ...osteoporosis via simple hip radiography using deep learning algorithm. A total of 1001 datasets of proximal femur DXA with matched same-side cropped simple hip bone radiographic images of female patients aged ≥ 55 years were collected. Of these, 504 patients had osteoporosis (T-score ≤ - 2.5), and 497 patients did not have osteoporosis. The 1001 images were randomly divided into three sets: 800 images for the training, 100 images for the validation, and 101 images for the test. Based on VGG16 equipped with nonlocal neural network, we developed a deep neural network (DNN) model. We calculated the confusion matrix and evaluated the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). We drew the receiver operating characteristic (ROC) curve. A gradient-based class activation map (Grad-CAM) overlapping the original image was also used to visualize the model performance. Additionally, we performed external validation using 117 datasets. Our final DNN model showed an overall accuracy of 81.2%, sensitivity of 91.1%, and specificity of 68.9%. The PPV was 78.5%, and the NPV was 86.1%. The area under the ROC curve value was 0.867, indicating a reasonable performance for screening osteoporosis by simple hip radiography. The external validation set confirmed a model performance with an overall accuracy of 71.8% and an AUC value of 0.700. All Grad-CAM results from both internal and external validation sets appropriately matched the proximal femur cortex and trabecular patterns of the radiographs. The DNN model could be considered as one of the useful screening tools for easy prediction of osteoporosis in the real-world clinical setting.
We find the realization of large converse magnetoelectric (ME) effects at room temperature in a magnetoelectric hexaferrite Ba0.52Sr2.48Co2Fe24O41 single crystal, in which rapid change of electric ...polarization in low magnetic fields (about 5 mT) is coined to a large ME susceptibility of 3200 ps/m. The modulation of magnetization then reaches up to 0.62μ(B)/f.u. in an electric field of 1.14 MV/m. We find further that four ME states induced by different ME poling exhibit unique, nonvolatile magnetization versus electric field curves, which can be approximately described by an effective free energy with a distinct set of ME coefficients.
Limited data are available regarding the management of subsolid nodules detected on lung cancer screening with low-dose CT (LDCT). We aimed to determine the characteristics of screen-detected ...subsolid nodules, and to evaluate the probability of lung cancer and the clinical course of subsolid nodules detected at baseline and during follow-up screening.
We evaluated 50 132 asymptomatic adults (22 631 never-smokers and 27 501 ever-smokers) who underwent LDCT screening for lung cancer between May 2003 and June 2019 at a tertiary centre in South Korea. The incidence, characteristics and clinical outcomes of the baseline and new screen-detected subsolid nodules were determined.
A total of 6725 subsolid nodules (5116 pure ground glass opacity nodules and 1609 part-solid nodules) were detected in 4545 participants (1484 new subsolid nodules detected in 937 (1.9%) participants; the overall incidence of subsolid nodules: 10.7% in never-smokers and 7.7% in ever-smokers, p<0.001). Among 4918 subsolid nodules that underwent follow-up with CT scans (the mean number of CT scans, including the baseline LDCT scan: 4.6), 2116 nodules (30.0% of baseline subsolid nodules and 78.9% of new subsolid nodules) resolved spontaneously. Among 293 biopsied subsolid nodules, 227 (77.5%) nodules were diagnosed as lung cancer, of which 226 (99.6%) were adenocarcinomas. No significant difference was observed in pathological invasiveness or the initial stage between the baseline and new cancerous subsolid nodules. Multivariable analyses revealed that new detection at follow-up screening was significantly associated with a lower probability of lung cancer (OR 0.26, 95% CI 0.14 to 0.49) and overall growth (OR 0.39, 95% CI 0.26 to 0.59), but with a higher probability of resolution (OR 6.30, 95% CI 5.09 to 7.81).
LDCT screening led to a considerably high rate of subsolid nodule detection, particularly in never-smokers. Compared with the baseline subsolid nodules, the new subsolid nodules were associated with a lower probability of lung cancer and higher probability of spontaneous resolution, indicating their more inflammatory nature. Less aggressive follow-up may be allowed for new subsolid nodules, particularly in screening programmes for Asian populations.
The hexapeptide WKYMVm, which is a strong formyl peptide receptor (FPR) 2 agonist, exhibits pro-angiogenic, anti-inflammatory and anti-apoptotic properties. However, its therapeutic efficacy in ...bronchopulmonary dysplasia (BPD) has not been tested to date. Here, we investigated whether WKYMVm attenuates hyperoxia-induced lung inflammation and ensuing injuries by upregulating FPR2. The proliferation and tube formation ability of human umbilical vein endothelial cells (HUVECs), along with the level of extracellular signal regulated kinase (ERK) phosphorylation, were evaluated in vitro. Newborn mice were randomly exposed to 80% oxygen or room air for 14 days starting at birth. WKYMVm (2.5 mg/kg) was intraperitoneally administrated daily from postnatal day (P) 5 to P8. At P14, mice were sacrificed for histopathological and morphometric analyses. Along with upregulation of FPR2 and p-ERK, WKYMVm promoted HUVEC cell proliferation and tube formation in vitro. Additionally, WKYMVm promoted proliferation of human pulmonary microvascular endothelial cells (HULEC-5a) and murine pulmonary endothelial and epithelial cells in vitro. WKYMVm significantly attenuated hyperoxia-induced lung inflammation, as evidenced by increased inflammatory cytokines, neutrophils, and alveolar macrophages, and resultant lung injuries, which included impaired alveolarization and angiogenesis, an increased number of apoptotic cells, and reduced levels of growth factors in vivo, such as vascular endothelial growth factor and hepatocyte growth factor. WKYMVm attenuates hyperoxia-induced lung injuries and lung inflammation by upregulating FPR2 and p-ERK.
The inhibition of p53 activity by histone deacetylase 3 (HDAC3) has been reported, but the precise molecular mechanism is unknown. Here we show that programmed cell death 5 (PDCD5) selectively ...mediates HDAC3 dissociation from p53, which induces HDAC3 cleavage and ubiquitin-dependent proteasomal degradation. Casein kinase 2 alpha phosphorylates PDCD5 at Ser-119 to enhance its stability and importin 13-mediated nuclear translocation of PDCD5. Genetic deletion of PDCD5 abrogates etoposide (ET)-induced p53 stabilization and HDAC3 cleavage, indicating an essential role of PDCD5 in p53 activation. Restoration of PDCD5(WT) in PDCD5(-/-) MEFs restores ET-induced HDAC3 cleavage. Reduction of both PDCD5 and p53, but not reduction of either protein alone, significantly enhances in vivo tumorigenicity of AGS gastric cancer cells and correlates with poor prognosis in gastric cancer patients. Our results define a mechanism for p53 activation via PDCD5-dependent HDAC3 decay under genotoxic stress conditions.
Preoperative body weight and nutritional status are related to prognosis in patients with gastric cancer; however, the prognostic impact of postoperative in these variables is unclear. We aimed to ...investigate the association of preoperative/postoperative body mass index (BMI) and prognostic nutritional index (PNI) with prognosis in patients with gastric cancer.
We retrospectively 1868 patients with stage II/III gastric cancer treated with gastrectomy between January 2006 and December 2010. We divided the populations into 3 groups according to BMI; underweight, normal, and overweight. Patients were divided into 3 groups according to BMI (underweight, normal-weight, overweight). PNI was classified into low and high (cutoff value; 49.7). The association of preoperative BMI/PNI and their changes (6 months postoperatively) with clinicopathologic characteristics were evaluated.
Preoperative underweight and low PNI were related to poor prognosis (log-rank p < 0.001 for both). There was a positive correlation between preoperative BMI and PNI (mean preoperative PNI: 51.13 underweight, 53.37 normal-weight, and 55.16 overweight; p < 0.001). Preoperative BMI and PNI were independent prognostic factors for disease-free survival along with age and TNM stage (p < 0.001 for both). BMI changes from normal-weight to underweight and from overweight to normal/underweight were related to poor prognosis (log-rank p = 0.021 and p = 0.013, respectively). PNI changes were related to prognosis in both the preoperative low and high PNI groups (p < 0.001 and p = 0.019, respectively).
Preoperative BMI and PNI and their postoperative changes are related to prognosis in patients with stage II/III gastric cancer. Careful nutritional intervention after gastrectomy can improve prognosis.
In acute promyelocytic leukemia (APL), increased cell burden in the peripheral blood due to either the disease itself or early treatment with all-trans retinoic acid could cause hyperleukocytosis ...(HL) before induction chemotherapy. However, therapeutic leukapheresis has seldom been used because of concerns of subsequent coagulopathy after this invasive procedure. The aim of this study was to evaluate the effects of leukapheresis in APL, especially for efficacy and safety.
We retrospectively analyzed newly diagnosed patients with APL from January 2009 to March 2022. Among 323 patients, 85 had white blood cell count above 40 × 109/L before induction chemotherapy. Thirty-nine patients were initially treated with leukapheresis, whereas the other 46 were not. Clinical and laboratory parameters between these groups were compared.
There was a trend toward favorable 30-day survival rate for the leukapheresis group compared with the non-leukapheresis group (76.9% and 67.4%; P = 0.24). The complications including subsequent intensive unit care (P = 0.23), severe hemorrhagic events (P = 0.13) showed no significant differences between the two groups. The patients were divided into subcohorts, and the survival rates of the leukapheresis and non-leukapheresis groups were 92.3% (95% confidence interval CI, 77.8%–100.0%) versus 58.3% (95% CI, 38.6%–78.1%) (P = 0.03) in “sequential HL” and 76.7% (95% CI, 61.5%–91.8%) versus 54.8% (95% CI, 37.3%–72.4%) (P = 0.03) in “symptomatic HL,” respectively. Moreover, in the “sequential HL” subcohort, the cumulative incidence of differentiation syndrome and following adverse events were significantly lower in the leukapheresis group.
In APL with “sequential HL” or “symptomatic HL” from either the disease itself or the effect of all-trans retinoic acid, therapeutic leukapheresis could be applied to reduce leukemic cell burden without significant risks.
Despite the enormous efforts to control the growth behavior of Li, achieving a dendrite‐free Li deposition and high‐energy‐density have remained an inevitable challenge of Li metal batteries. Here, ...the conformal deposition of Li metal is reported on electroactive organic materials to achieve a high‐energy‐density and electrochemical longevity. To this end, Li2C8H4O4 (Li2TP), which can act as both the electrode material (providing the redox capacity) and Li host (inducing the dendrite‐free Li deposition), is used as the model electroactive organic material. The Li2TP host exhibits reversible sequential lithiation/delithiation and Li deposition/stripping reactions. Consequently, a Li‐free full cell constructed by the Li2TP host (without pre‐charging) and a LiFePO4 cathode delivered a high areal capacity (≈3.8 mAh cm−2), exceptional rate performance (≤12 mA cm−2), and superior cyclability (80% capacity retention after 100 cycles). This electroactive organic material‐based Li host strategy can provide a new perspective for the development of practical Li metal batteries.
A conformal and dendrite‐free deposition of lithium metal on electroactive organic materials (Li2C8H4O4) is demonstrated, which can achieve both redox capacity and lithium electrodeposition stabilization. This work provides a new design concept for electroactive Li hosts that enable practical Li metal batteries with high energy density and electrochemical longevity.
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