Current status and value of testing antiphospholipid antibody in patients with acute ischemic stroke: a retrospective single-center study in China.

BACKGROUND AND PURPOSE: Testing for antiphospholipid antibodies (aPL) is useful to determine the cause of ischemic stroke in young and female patients. However, the clinical relevance of aPL in older patients with ischemic stroke remains unclear. We aimed to explore the status and diagnostic value of initial aPL testing in all patients with acute ischemic stroke. METHODS: We retrospectively analyzed patients with acute ischemic stroke who were consecutively hospitalized in our hospital between June 2012 and January 2022 and investigated the factors associated with performing aPL screening in real-world clinical practice. Furthermore, factors associated with initial aPL positivity were evaluated by comparing the demographic, etiological, and therapeutic characteristics. RESULTS: Of 1209 patients, 287 (23.7%) were tested for aPL and 58 (20.2%) tested positive. Physicians tended to conduct aPL testing on female patients (P<0.001), younger patients (P<0.001), patients with fewer vascular risk factors (P<0.001), and multiple infarctions in the multivascular blood supply area (P<0.001). Multivariate logistic regression analysis showed that only stroke of other determined etiology type was a significant influencing factor for positive aPL results (OR 2.97, 95% CI 1.137, 7.774, P=0.026), adjusting for sex, age, and causes of stroke, etc. CONCLUSION: Approximately one-quarter of the patients with acute ischemic stroke were tested for aPL. Age, sex, number of vascular risk factors, and neuroimaging features affected the discretion in performing aPL testing. aPL testing may be appropriate in older patients with no identified cause of ischemic stroke and may provide additional diagnostic opportunities for acute ischemic stroke.

Clear cell sarcoma in the post-molar area: Report of an ultra-rare case and literature review of oral clear cell sarcoma.

BACKGROUND: Clear cell sarcoma of soft tissue is an exceptionally rare sarcoma. It is even rarer in the oral cavity. To our knowledge, this case is the first reported clear cell sarcoma involving the post-molar area. Pathologically, clear cell sarcoma has low mitotic activity, rare nuclear pleomorphism, and necrosis. Its biological behavior is often underestimated by morphology. It is a highly aggressive tumor. CASE REPORT: A 39-year-old female presented with an asymptomatic mass in the post-molar area. It was mistaken for a benign or low-grade malignant tumor based on frozen incisional biopsy samples. The surgical resection sample was tested by NGS, which detected a rare EWSR1::CREB1 in clear cell sarcoma. The final diagnosis was made by combining morphological, immunohistochemical, and molecular test results. The patient did not receive any adjuvant therapy after surgery and no recurrence of the disease was detected at 8 months of follow-up. CONCLUSION: The study highlights that mild histological manifestation in the oral cavity should be considered the possibility of CCS affecting young patients. Careful histological investigation, sufficient immunohistochemical staining, and molecular tests are essential to the diagnosis.

Case report: Misdiagnosis of primary mucinous cystadenoma of the testicle by ultrasound.

Testicular mucinous cystadenoma is a rare benign testicular tumor with the characteristics of being potentially malignant and showing atypical clinical symptoms; this article reports a case of a primary testicular mucinous cystadenoma misdiagnosed as testicular teratoma by ultrasound. A 69-year-old man was admitted to the hospital because of a 1-year history of left-sided testicular enlargement with scrotal swelling and no obvious abnormalities on laboratory tests. Ultrasound examination revealed solid-mass lesions in the left testicle, suggesting a high probability of teratoma, and contrast-enhanced magnetic resonance imaging (MRI) examination suggested an increased possibility of epidermoid cysts. Contrast-enhanced computed tomography (CT) and contrast-enhanced MRI of the preoperative abdomen and pelvis showed no other primary adenocarcinoma. Doctors performed radical resection of the left testicle. The postoperative pathological diagnosis was mucinous cystadenoma, and calcification as well as partially mildly atypical epithelial cells were discovered. Furthermore, there were no neoplastic lesions in the epididymis or spermatic cord. No metastatic lesions were found after 6 months postoperative follow-up, and the patient's prognosis remains good.

Mechanisms of in-hospital acute ischemic stroke and their relevance to prognosis: A retrospective analysis.

OBJECTIVES: In-hospital stroke (IHS) is common and has a poor prognosis. Limited data were about the mechanisms of IHS, posing a challenge in taking measures to prevent stroke during hospitalization. This study aims to investigate the mechanisms of IHS and their relevance to prognosis. MATERIALS AND METHODS: Patients with in-hospital acute ischemic stroke at Peking Union Medical College Hospital from June 2012 to April 2022 were consecutively enrolled. The Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of stroke and detailed mechanisms were evaluated by two experienced neurologists. Functional outcome at discharge was evaluated. RESULTS: A total of 204 IHS patients were included, with a median age of 64 (IQR 52-72) and 61.8% male. The most common mechanism was embolism (57.8%), followed by hypoperfusion (42.2%), hypercoagulation (36.3%), small vessel mechanism (19.1%), discontinuation of antithrombotic drugs (13.2%), and iatrogenic injury (9.8%). Iatrogenic injury (P = 0.001), hypoperfusion (P = 0.006), embolism (P = 0.03), and discontinuation of antithrombotic drugs (P = 0.004) were more common in perioperative stroke compared to non-perioperative stroke. Median NIHSS improvement (2 vs 1, P = 0.002) and median mRS improvement (1 vs 0.5, P = 0.02) at discharge were higher in perioperative patients. Advanced age and higher NIHSS at onset were significantly associated with a poorer prognosis, whereas embolism mechanism was associated with a better prognosis. CONCLUSIONS: The etiologies and mechanisms of IHS are complex. Perioperative and non-perioperative IHS have different mechanisms and prognostic features. Determining the causes and mechanisms of IHS will help to identify the population at risk and prevent stroke appropriately during hospitalization.

The clinicopathological and prognostic significances of IGF-1R and Livin expression in patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide. However, limited effective biomarkers are associated with the tumorigenesis and prognosis of CRC. METHODS: The present study identified potential signatures from The Cancer Genome Atlas (TCGA) database and further validated the identified biomarkers in CRC tissues by immunohistochemistry (IHC). RESULTS: The expression of insulin-like growth factor 1 receptor (IGF-1R) and Livin gene was significantly upregulated in CRC samples compared to the adjacent normal samples in the TCGA dataset. IHC indicated that IGF-1R and Livin protein levels are increased in CRC and adenoma tissues compared to normal tissues. Notably, the IGF-1R protein levels differed significantly between adenoma and CRC. The elevated IGF-1R and Livin expression was associated with CRC clinicopathological features, including age, gender, histological subtype, individual cancer stages, nodal metastasis, and TP53-mutant in TCGA. Additionally, the IGF-1R promoter methylation level was closely related to CRC. Consistent with the TCGA study, IHC indicated that overexpressed IGF-1R and Livin proteins were independent risk factors for stage and metastasis. A marked correlation was established between IGF-1R and Livin expression in CRC, while the survival map showed no significant correlation with CRC. Kaplan-Meier survival curves showed that CRC patients with high IGF-1R or Livin expression had a prolonged overall disease-free survival than those with low expression in TCGA. CONCLUSION: IGF-1R and Livin are associated with CRC tumorigenesis and might be valuable for novel biomarker identification and targeted therapeutic strategy development.

Investigating the Genetic Characteristics of Hippocampal Volume and Plasma ß-Amyloid in a Chinese Community-Dwelling Population.

BACKGROUND AND OBJECTIVES: The genetic characteristics and correlations of hippocampal volume and plasm Aß, probable endophenotypes for dementia, remain to be explored in Chinese community cohort. Using whole-exome sequencing and SNP-array genotyping, we sought to identify rare and common variants and genes influencing these two endophenotypes, and calculate their heritability and genetic correlation. METHODS: Association analyses with both whole-exome sequencing and SNP-array genotyping data were performed for hippocampal volumes and plasm Aß with mixed-effect linear regression model adjusted for sex, age, and total intracranial volume or APOE ε4 while considering familial relatedness. We also performed gene-level analysis for common and gene-burden analysis for rare variants. Heritability and genetic correlation were further examined. RESULTS: Totally 1,261 participants from a Chinese community cohort were included and we identified one gene, PTPRT, for hippocampal volume, with the top significant SNPs by whole genome-wide association study. rs6030076 (P=5.48×10-8, ß=-0.092, SE=0.017) from whole-exome sequencing and rs6030088 (P=8.24×10-9, ß=-105.22 SE=18.09) from SNP-array data, both located in this gene. Gene-burden analysis based on rare mutations detected 6 genes to be significantly associated with Aß. The SNP-based heritability was 0.43±0.13 for hippocampal volume and 0.2-0.3 for plasma Aß. The SNP-based genetic correlation between hippocampal volume and plasma Aß were negative. DISCUSSION: In this study, we identified several SNPs and one gene, PTPRT, which were not reported in previous GWASs, associated with hippocampal volume. Besides, the heritability and the genetic correlation gave an overview of hippocampal volume and plasma Aß. Our findings provide insights into the mechanisms behind the individual variances in these endophenotypes.

Soft tissue sarcoma: IVIM and DKI parameters correlate with Ki-67 labeling index on direct comparison of MRI and histopathological slices.

OBJECTIVES: To explore the correlation of parameters derived from intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) with Ki-67 labeling index (LI) in soft tissue sarcoma (STS). METHODS: Forty-one patients with STS underwent IVIM and DKI imaging at 3.0 MRI. The standard apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), perfusion fraction (f), mean kurtosis (MK), and mean diffusivity (MD) were compared between Ki-67 low- and high-expression groups by two independent observers. A novel method was used to ensure the topographic correlation of histologic sections and magnetic resonance imaging slices. Receiver operating characteristic (ROC), intraclass correlation coefficient (ICC), and Spearman's rank correlations were performed for statistical analysis. RESULTS: The high-expression group displayed lower standard ADC, D, and MD values and a higher MK value than the low-expression group. No significant differences were found for D∗ and f values. The areas under the curve for standard ADC, D, MD, and MK when discriminating between low- and high-expression groups were 0.736, 0.745, 0.848, and 0.894, respectively. MK was positively correlated with Ki-67 LI (r = 0.809, p < 0.001). Standard ADC, D, and MD were negatively correlated with Ki-67 LI (r = -0.541, -0.556, -0.702, respectively, p < 0.001). CONCLUSIONS: IVIM and DKI parameters are correlated with Ki-67 LI. MK may be the optimal imaging biomarker for assessing the Ki-67 expression of STS. KEY POINTS: • IVIM and DKI parameters are correlated with the expression of Ki-67 in STS. • The MRI-pathology control method ensured a strong correlation between MRI slices and histologic sections, resulting in a robust radiological-pathological correlation.

Prognostic nomogram incorporating radiological features for predicting overall survival in patients with AIDS-related non-Hodgkin lymphoma.

BACKGROUND: Acquired immune deficiency syndrome (AIDS)-related non-Hodgkin lymphoma (AR-NHL) is a high-risk factor for morbidity and mortality in patients with AIDS. This study aimed to determine the prognostic factors associated with overall survival (OS) and to develop a prognostic nomogram incorporating computed tomography imaging features in patients with acquired immune deficiency syndrome-related non-Hodgkin lymphoma (AR-NHL). METHODS: A total of 121 AR-NHL patients between July 2012 and November 2019 were retrospectively reviewed. Clinical and radiological independent predictors of OS were confirmed using multivariable Cox analysis. A prognostic nomogram was constructed based on the above clinical and radiological factors and then provided optimum accuracy in predicting OS. The predictive accuracy of the nomogram was determined by Harrell C-statistic. Kaplan-Meier survival analysis was used to determine median OS. The prognostic value of adjuvant therapy was evaluated in different subgroups. RESULTS: In the multivariate Cox regression analysis, involvement of mediastinal or hilar lymph nodes, liver, necrosis in the lesions, the treatment with chemotherapy, and the CD4 ≤100 cells/µL were independent risk factors for poor OS (all P < 0.050). The predictive nomogram based on Cox regression has good discrimination (Harrell C-index = 0.716) and good calibration (Hosmer-Lemeshow test, P = 0.620) in high- and low-risk groups. Only patients in the high-risk group who received adjuvant chemotherapy had a significantly better survival outcome. CONCLUSION: A survival-predicting nomogram was developed in this study, which was effective in assessing the survival outcomes of patients with AR-NHL. Notably, decision-making of chemotherapy regimens and more frequent follow-up should be considered in the high-risk group determined by this model.

Soft tissue sarcomas: IVIM and DKI correlate with the expression of HIF-1α on direct comparison of MRI and pathological slices.

OBJECTIVE: To investigate the correlation of intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) parameters with the expression of HIF-1α in soft tissue sarcoma (STS). METHODS: This prospective study was approved by the institutional ethics committee. Written informed consent was obtained from all patients. Forty patients with STS who underwent 3.0 T MRI, including IVIM and DKI, were included in the study. Standard apparent diffusion coefficient (ADC), true ADC (Dslow), pseudo ADC (Dfast), perfusion fraction (f), mean kurtosis (MK), and mean diffusivity (MD) of each lesion were independently analyzed by two observers. An MRI-pathology control method was used to ensure correspondence between the MRI slices and the pathological sections. Spearman analysis, independent sample t test, Mann-Whitney U test, chi-squared test, and receiver operating characteristic (ROC) curve analysis were performed. RESULTS: Dslow and MD values showed a negative correlation with HIF-1α expression (r = - 0.469, - 0.588). MK and f values showed a positive correlation with HIF-1α expression (r = 0.779, 0.572). Dslow, MD, MK, and f values showed significant differences between the high- and low-expression groups. The MK value showed the best diagnostic ability. The optimal cut-off MK value of 0.604 was associated with 78.3% sensitivity and 88.2% specificity (area under the curve, 0.867). CONCLUSIONS: This preliminary study demonstrated the association of IVIM and DKI parameters with the expression of HIF-1α in STS. KEY POINTS: • IVIM and DKI parameters are correlated with the expression of HIF-1α in STS. • The MRI-pathology control method can be used in clinical studies to ensure correspondence between MRI slices and pathology sections.

Clinical and CT characteristics which indicate timely radiological reexamination in patients with COVID-19: A retrospective study in Beijing, China.

OBJECTIVE: Chest CT is useful in assessing the disease course of coronavirus disease-19 (COVID-19). This study aims to identify the characteristics of patients in whom imaging progression occurred while clinical symptoms were relieved and to guide radiological reexamination. METHODS: This retrospective study included 73 patients with reverse transcription-polymerase chain reaction (RT-PCR) confirmed severe acute respiratory syndrome-2 (SARS-CoV-2) infection. All patients received CT reexaminations within 24 h after symptomatic remission. We divided patients into two groups according to the matching degree between clinical and imaging outcomes. RESULTS: 21 patients displayed imaging progression while symptoms relieved. Patients with imaging progression were prone to be advanced in age [years: 60 (46-65) v 47 (37-60.75), P = 0.030]; lymphopenia (66.7% v 40.4%, P = 0.042) and low level of C-reactive protein [mg/L: 5.7 (1.9-20.2) v 18.9 (6.7-38.9), P = 0.038]. An age over 50 was an independent risk factor for imaging progression (OR = 3.41, 95%CI 1.14-10.20, P = 0.028). In CT images, they were inclined to present lesions with clear border (94.7% v 64.7%, P = 0.012), pure peripheral distribution (89.5% v 39.2%, P < 0.001), without bilateral lungs involved (57.9% v 29.4%, P = 0.028) especially with left lung involved only (42.1% v 17.6%, P = 0.034). CONCLUSION: In order to improve the therapeutic effect, the interval before radiological follow-up should be shortened appropriately especially in patients over the age of 50. It is essential to proceed to CT reexamination before symptomatic remission.

Sphingosine-1-phosphate attenuates hypoxia/reoxygenation-induced cardiomyocyte injury via a mitochondrial pathway.

Our previous study showed that Sphingosine-1-phosphate (S1P) could protect cardiomyocytes against hypoxia/reoxygenation (H/R) injury via the JAK-STAT pathway and maintain normal myocardial mitochondria integrity in vivo. However, it is not known yet whether S1P can relieve mitochondrial dysfunction via the mitochondrial apoptotic pathway and its detailed mechanism remains to be investigated. The aim of this study was to demonstrate the mitochondrial protective effects of S1P in a cardiomyocyte H/R injury model. In the present study, we established a H/R model in H9c2 cells. Cell viability was determined by the MTT assay, and apoptosis was evaluated by annexin V-FITC/PI staining. Mitochondrial calcium ion concentration, mitochondrial membrane potential (ΔΨm), opening of the mitochondrial permeability transition pore (mPTP), and release of cytochrome C were detected by laser confocal microscopy. The results showed that S1P inhibited the decrease in cell viability induced by H/R injury and reduced apoptosis. Confocal microscopy showed that S1P prevented loss of ΔΨm, relieved mitochondrial calcium overload, and inhibited opening of the mPTP and release of cytochrome C. The STAT3 inhibitor STATTIC can reverse the antiapoptotic effects of S1P and block the effect of S1P on mitochondria. Taken together, our results indicate that S1P protects cardiomyocytes against H/R injury by relieving mitochondrial dysfunction via the STAT3 pathway.