Type A Aortic Dissection in Heart Transplantation Recipients in the United States.

BACKGROUND: Type A aortic dissection in heart transplantation recipients is rare and lethal, with limited research beyond case reports. This study aimed to analyze patient characteristics and clinical outcomes of this condition through a US national database. METHODS: The National Inpatient Sample database (2002-2018) was used to identify all type A aortic dissection in heart transplantation recipients aged >18 years. Incidence was quantified annually. Primary outcomes were in-hospital mortality; secondary outcomes were hospital length of stay and complications. RESULTS: We identified 78 cases of type A aortic dissection in heart transplantation recipients. Compared with type A aortic dissection patients without a history of solid organ transplantation (N = 70,715), our patients were younger (55.3 vs 60.7 years), less likely female (18.5% vs 33.5%), and more frequently Black or Hispanic (55% vs 23%). They had a greater prevalence of Marfan syndrome (13% vs 3%), congestive heart failure (46% vs 19%), and chronic kidney disease (19% vs 10%), as well as increased in-hospital mortality (30% vs 18%) and a longer hospital length of stay (29.5 vs 13.7 days). They experienced elevated rates of cardiac (57% vs 31%), respiratory (70. % vs 41%), renal (76% vs 30%), and bleeding complications (37% vs 14%). CONCLUSIONS: Type A aortic dissection in heart transplantation recipients appears to exhibit distinct characteristics and poorer outcomes compared with those in the general population. Heart transplantation recipients with predisposing risk factors warrant heightened attention to help prevent this devastating condition.

Aortic Dissection During Pregnancy and Puerperium: Contemporary Incidence and Outcomes in the United States.

Background Aortic dissection (AD) during pregnancy and puerperium is a rare catastrophe with devastating consequences for both parent and fetus. Population-level incidence trends and outcomes remain relatively undetermined. Methods and Results We queried a US population-based health care database, the National Inpatient Sample, and identified all patients with a pregnancy-related AD hospitalization from 2002 to 2017. In total, 472 pregnancy-related AD hospitalizations (mean age, 30.9±0.6 years) were identified from 68 514 000 pregnancy-related hospitalizations (0.69 per 100 000 pregnancy-related hospitalizations), with 107 (22.7%) being type A and 365 (77.3%) being type B. The incidence of AD appeared to increase over the 16-year study period but was not statistically significant (P for trend >0.05). Marfan syndrome, primary hypertension, and preeclampsia/eclampsia were found in 21.9%, 14.4%, and 11.5%, respectively. On multivariable logistic regression analysis, Marfan syndrome was associated with the highest risk of developing AD during pregnancy and puerperium (adjusted odds ratio, 3469.36 [95% CI, 1767.84-6831.75]; P<0.001). The in-hospital mortalities of AD, type A AD, and type B AD were 7.3%, 4.3%, and 8.1%, respectively. Length of hospital stay for the AD, type A AD, and type B AD groups were 7.7±0.8, 10.4±1.9, and 6.9±0.9 days, respectively. Conclusions We quantified population-level incidence and in-hospital mortality in the United States and observed an increase in the incidence of pregnancy-related AD. In contrast, its in-hospital mortality appears lower than that of non-pregnancy-related AD.

N6-Methyladenosine-modified lncRNA LINREP promotes Glioblastoma progression by recruiting the PTBP1/HuR complex.

Glioblastoma multiforme (GBM) is acknowledged as the most aggressive primary brain tumor in adults. It is typically characterized by the high heterogeneity which corresponds to extensive genetic mutations and complex alternative splicing (AS) profiles. Known as a major repressive splicing factor in AS, polypyrimidine tract-binding protein 1 (PTBP1) is involved in the exon skipping events of multiple precursor mRNAs (pre-mRNAs) in GBM. However, precise mechanisms that modulate the expression and activity of PTBP1 remain to be elucidated. In present study, we provided evidences for the role of a long intergenic noncoding RNA (LINREP) implicated in the regulation of PTBP1-induced AS. LINREP interacted with PTBP1 and human antigen R (HuR, ELAVL1) protein complex and protected PTBP1 from the ubiquitin-proteasome degradation. Consequently, a broad spectrum of PTBP1-induced spliced variants was generated by exon skipping, especially for the skipping of reticulon 4 (RTN4) exon 3. Interestingly, LINREP also promoted the dissociation of nuclear UPF1 from PTBP1, which increased the binding of PTBP1 to RTN4 transcripts, thus enhancing the skipping of RTN4 exon 3 to some extent. Besides, HuR recruitment was essential for the stabilization of LINREP via a manner dependent on N6-methyladenosine (m6A) formation and identification. Taken together, our results demonstrated the functional significance of LINREP in human GBM for its dual regulation of PTBP1-induced AS and its m6A modification modality, implicating that HuR/LINREP/PTBP1 axis might serve as a potential therapeutic target for GBM.

Association of Intravenous Drug Use and Length of Stay Following Infective Endocarditis.

INTRODUCTION: Intravenous drug use (IVDU) and associated infective endocarditis (IE) has been on the rise in the US since the beginning of the opioid epidemic. IVDU-IE has high morbidity and mortality, and treatment can be lengthy. We aim to quantify the association between IVDU and length of stay (LOS) in IE patients. METHODS: The National Inpatient Sample database was used to identify IE patients, which was then stratified into IVDU-IE and non-IVDU-IE groups. Weighted values of hospitalizations were used to generate national estimates. Multivariable linear and logistic regression analyses were applied to estimate the effects of IVDU on LOS. RESULTS: We identified 1,114,257 adult IE patients, among which 123,409 (11.1%) were IVDU-IE. Compared to non-IVDU-IE patients, IVDU-IE patients were younger, had fewer comorbidities, and had an overall longer LOS (median [interquartile range]: 10 [5-20] versus 7 [4-13] d, P < 0.001), with a greater percentage of patients with a LOS longer than 30 d (13.7% versus 5.7%, P < 0.001). After adjusting for multiple demographic and clinical factors, IVDU was independently associated with a 1.25-d increase in LOS (beta-coefficient = 1.25, 95% confidence interval [CI]: 0.95-1.54, P < 0.001) and 35% higher odds of being hospitalized for more than 30 d (odds ratio = 1.35, 95% CI: 1.27-1.44, P < 0.001). CONCLUSIONS: Among IE patients, being IVDU has associated with a longer LOS and a higher risk of prolonged hospital stay. Steps toward the prevention of IE in the IVDU population should be taken to avoid an undue burden on the healthcare system.

Changes in treatment patterns of thoracoabdominal aortic aneurysms in the United States.

Background: The introduction of endovascular repair provides an alternative to traditional open repair of thoracoabdominal aortic aneurysms (TAAA). Its utility is not well defined, however. Using a national database, we studied the treatment patterns and outcomes of TAAA to gain insight into its contemporary surgical practice in the United States. Methods: Records of TAAA patients who received endovascular and open repair were retrieved from the 2002 to 2018 National Inpatient Sample database. Each cohort was stratified into 4 age groups: ≤50, 51 to 60, 61 to 70, and >70 years. Patient characteristics and in-hospital outcomes were compared between the 2 repair modalities. Temporal trends were investigated. Results: Endovascular repair use increased steadily, whereas open repair volume remained stable until 2012, before declining by 50% by 2018. This appears to be associated with a declining number of open repairs in patients age >60 years. Patients who underwent endovascular repair were older and had a higher Charlson Comorbidity Index (mean, 2.8 ± 1.7 vs 2.5 ± 1.5; P < .001) but lower in-hospital mortality (mean, 8.9% vs 17.1%; P < .001), shorter length of stay (mean, 10.1 ± 12.2 days vs 17.1 ± 17.4 days; P < .001), and fewer postoperative complications. A difference in mortality between open and endovascular repair was observed for patients age >60 years but not for patients age ≤60 years. Conclusions: There has been a shift in the treatment of TAAA in the United States from open repair-dominant to endovascular repair-dominant. It has increased surgical access for older and more comorbid patients and has led to a decline in the use of open repair while lowering in-hospital mortality.

Rare malignant primary spinal intradural extramedullary mesenchymal chondrosarcoma: a case report and literature review.

Background: Mesenchymal chondrosarcoma (MCS) is a rare malignant chondrosarcoma with a high propensity for recurrence and distant metastasis. MCS usually arises from bone tissue, and rarely occurs outside the bone. MCS in the subdural and extramedullary regions of the spinal cord is especially rare. In this article, we report a case of spinal intradural extramedullary MCS with herpes virus infection, which is the first such case reported in East China. Case Description: A 13-year-old male complained of intermittent low-grade fever, sweating, progressive constipation with weakness of both lower extremities and bilateral hypoesthesia after a 5-month history of herpes virus infection. Spinal magnetic resonance imaging (MRI) revealed a subdural-extramedullary solid nodular mass with isointensity on T1-weighted imaging and hyperintensity on T2-weighted imaging that was located behind the superior margin of the T5 vertebral body. The patient was initially diagnosed with thoracic meningioma and underwent spinal cord tumour resection followed by adjuvant chemotherapy. Histopathological examination revealed that the tumour was mainly composed of round or oval cells and mesenchymal chondroid matrix, and gene analysis showed the fusion of HEY1 exon 4 to NCOA2 exon 13. Both test results were consistent with the diagnosis of primary intraspinal MCS. At the 1-year follow-up, the patient received adjuvant chemotherapy, and the reexamination images revealed no evidence of tumour in situ tumour recurrence or distant metastasis. Conclusions: As more research has been done on MCS, it has been found that the disease is more likely to occur in adolescents, but is often overlooked due to its lack of imaging characterization. Therefore, the misdiagnosis rate can be reduced only by closely considering clinical manifestations with pathology and imaging findings. Although MCS is a highly malignant tumour, early primary spinal intradural extramedullary MCS can cause neurological symptoms, early detection and treatment can achieve basic total surgical resection. Postoperative adjuvant chemoradiotherapy can further reduce recurrence.

Efficacy and Safety of Low-Dose Rituximab in Anti-MuSK Myasthenia Gravis Patients: A Retrospective Study.

Purpose: To evaluate the efficacy and safety of low dosages of rituximab (RTX) in the treatment of MuSK-antibody-positive MG patients. Patients and Methods: We retrospectively analyzed the data of MuSK-antibody-positive MG patients who were treated with low dosages of RTX from January 2018 to October 2021. The long-term treatment response to RTX was assessed by Myasthenia Gravis Foundation of America (MGFA) post-interventional status (PIS), Myasthenia Gravis Status and Treatment Intensity (MGSTI), dosage of steroid, MG-related activities of daily living (MG-ADL) and myasthenic muscle score (MMS) at the end of follow-up. Results: Clinical improvement was observed in all eight patients with follow-up for 8 to 29 months after treatment. At the last visit, complete stable remission had been achieved in one patient, pharmacologic remission in three patients, minimal manifestations status in three patients and improved in one patient based on the MGFA-PIS criteria. MGSTI level 2 or better had been reached in six (75%) patients at the last visit. The steroid dosage decreased from 60 mg at baseline to 15 mg at the last follow-up (p = 0.011). The average MG-ADL score decreased from 11 (range 7 to 15) to 0 (range 0 to 3; p = 0.011), and the MMS improved from 38.5 (range 24 to 60) to 100 (range 90 to 100; p = 0.012). These differences were all statistically significant. During RTX treatment and subsequent follow-up, 1 patient reported minor post-infusion malaise. Conclusion: Low-dose RTX is effective and safe for treating anti-MuSK antibody positive MG patients. A long-term response is observed after treatment. Larger prospective studies are required to provide further evidence.

Surgical outcomes of pulmonary valve infective endocarditis: A US population-based analysis.

BACKGROUND: Pulmonary valve infective endocarditis (PVIE) represents a rare subset of right-sided IE. This study aimed to evaluate the population-level surgical outcomes of PVIE in the United States. METHODS: We performed a retrospective observational study using the 2002-2017 National Inpatient Sample database. We included hospitalizations with both IE and PV interventions. We excluded Tetralogy of Fallot, congenital PV malformation, and those who underwent the Ross procedure. The primary outcome was in-hospital mortality. The secondary outcomes included major complications and length of hospital stay. RESULTS: We identified 677 PVIE hospitalizations that underwent surgical treatment, accounting for 0.06% of all IE hospitalizations. The mean age was 35.2 ± 1.7 years; 60.0% were White, 30.3% were women, and 11.4% were intravenous drug users. Most were treated in large-sized (70.1%) urban teaching (88.8%) hospitals. Close to 30% of patients received at least one concomitant valve procedure. The in-hospital mortality was 5.5% for the entire cohort, and the median length of stay was 16 days. Major complications included complete heart block (8.7%), acute kidney injury (8.1%), and stroke (1.3%). The differences in mortality and complications rate comparing PV repair and replacement were not statistically significant. PV repair was associated with a longer length of hospital stay compared to PV replacement (median: 25 vs. 16 days, p = 0.03). CONCLUSIONS: This study defines the population-level in-hospital outcomes after surgical intervention of PVIE. Surgically treated PVIE patients are associated with relatively low mortality and morbidities. The outcomes between PV replacement and repair are similar.

Expression and clinical significance of organic cation transporter family in glioblastoma multiforme.

BACKGROUND: Solute carrier (SLC) 22 A1, A2, and A3 are polyspecific transporters transporting organic cations like histamine, serotonin, norepinephrine, dopamine, MPP + , and toxins. The expression of SLC22A1-A3 in cancer is seldom investigated, and the function of SLC22A1-A3 in glioblastoma multiforme (GBM) is never elucidated. MATERIALS: In our study, we detected the expression of SLC22A1-A3 in 11 fresh GBMs and tumor-adjacent brain tissues with qPCR, and in 129 paraffin-embedded GBMs with immunohistochemistry (IHC). With chi-square test, we investigated the correlation between expression of SLC22A1-A3 and the clinicopathological factors including patients' age, sex, tumor size, and KPS score. With Kaplan-Meier method and Cox-regression model, we estimated the prognostic significance of SLC22A1-A3 in GBM. RESULTS: SLC22A3 was significantly downregulated in GBMs compared with the tumor-adjacent normal tissues. With univariate survival analyses, we showed that SLC22A3, instead of SLC22A1 and A2, was an independent biomarker predicting favorable prognosis. With multivariate analyses, SLC22A3 was identified as an independent prognostic biomarker indicating the favorable outcome of GBM. CONCLUSIONS: SLC22A3 is an independent favorable prognostic biomarker of GBM. Patients with low SLC22A3 may be more high-risk and should receive more intensive post-operational supervision and treatments.

Immune-Related Gene SERPINE1 Is a Novel Biomarker for Diffuse Lower-Grade Gliomas via Large-Scale Analysis.

BACKGROUND: Glioma is one of the highly fatal primary tumors in the central nervous system. As a major component of tumor microenvironment (TME), immune cell has been proved to play a critical role in the progression and prognosis of the diffuse lower-grade gliomas (LGGs). This study aims to screen the key immune-related factors of LGGs by investigating the TCGA database. METHODS: The RNA-sequencing data of 508 LGG patients were downloaded in the TCGA database. ESTIMATE algorithm was utilized to calculate the stromal, immune, and ESTIMATE scores, based on which, the differentially expressed genes (DEGs) were analyzed by using "limma" package. Cox regression analysis and the cytoHubba plugin of Cytoscape software were subsequently applied to screen the survival-related genes and hub genes, the intersection of which led to the identification of SERPINE1 that played key roles in the LGGs. The expression patterns, clinical features, and regulatory mechanisms of SERPINE1 in the LGGs were further analyzed by data mining of the TCGA database. What's more, the above analyses of SERPINE1 were further validated in the LGG cohort from the CGGA database. RESULT: We found that stromal and immune cell infiltrations were strongly related to the prognosis and malignancy of the LGGs. A total of 54 survival-related genes and 46 hub genes were screened out in the DEGs, within which SERPINE1 was identified to be significantly overexpressed in the LGG samples compared with the normal tissues. Moreover, the upregulation of SERPINE1 was more pronounced in the gliomas of WHO grade III and IDH wild type, and its expression was correlated with poor prognosis in the LGG patients. The independent prognostic value of SERPINE1 in the LGG patients was also confirmed by Cox regression analysis. In terms of the functions of SERPINE1, the results of enrichment analysis indicated that SERPINE1 was mainly enriched in the immune-related biological processes and signaling pathways. Furthermore, it was closely associated with infiltrations of immune cells in the LGG microenvironment and acted synergistically with PD1, PD-L1, PD-L2. CONCLUSION: These findings proved that SERPINE1 could serve as a prognostic biomarker and potential immunotherapy target of LGGs.

Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker FAM111A in Diffuse Lower-Grade Glioma.

BACKGROUND: Family with sequence similarity 111 member A (FAM111A), as a replication factor required for proliferating cell nuclear antigen (PCNA) loading, has been demonstrated a possible association with carcinogenesis. However, the role of FAM111A in lower-grade glioma (LGG) remains unclear. We aim at investigating the expression and function of FAM111A in lower-grade glioma at the molecular and clinical levels. METHODS: In total, 711 lower-grade glioma samples were analyzed in our research, including 182 RNA-seq data from the Chinese Glioma Genome Atlas (CGGA) dataset and 529 RNA-seq data from The cancer Genome Atlas (TCGA) dataset. R language and the GraphPad software were used for the majority of statistical analysis and graphical work. RESULTS: FAM111A expression was overexpressed in WHO grade III and IDH-wildtype lower-grade glioma. FAM111A was significantly downregulated in the IDHmut-Codel molecular subtype. Univariate and multivariate Cox analysis demonstrated that FAM111A was an independent prognostic factor in LGG patients. Functional characterization of FAM111A revealed that it was associated with inflammatory response and immune response to tumor cells. FAM111A could also act as an indicator of the stromal and immune population, especially for monocytic lineage, myeloid dendritic cells and fibroblasts. It was positively correlated with macrophages, especially the M2 macrophage cells. Furthermore, FAM111A revealed predictive value for the immune subtypes and immune checkpoint blockade therapy. CONCLUSION: FAM111A expression was closely related to the malignant phenotype, molecular pathology and immune response of lower-grade glioma. It might be a promising target for LGG immunotherapeutic strategies.

A high-performance solid-state electrocaloric cooling system.

Electrocaloric (EC) cooling is an emerging technology that has broad potential to disrupt conventional air conditioning and refrigeration as well as electronics cooling applications. EC coolers can be highly efficient, solid state, and compact; have few moving parts; and contain no environmentally harmful or combustible refrigerants. We report a scalable, high-performance system architecture, demonstrated in a device that uses PbSc0.5Ta0.5O3 EC multilayer ceramic capacitors fabricated in a manufacturing-compatible process. We obtained a system temperature span of 5.2°C and a maximum heat flux of 135 milliwatts per square centimeter. This measured heat flux is more than four times higher than other EC cooling demonstrations, and the temperature lift is among the highest for EC systems that use ceramic multilayer capacitors.