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Interferon-Induced Transmembrane Protein 1 (IFITM1) Is Downregulated in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors
Get PDFNeurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, is caused by mutations in the NF1 gene, which encodes the GTPase-activating protein neurofibromin. The pathogenesis of the tumor progression of benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. Here, we found that interferon-induced transmembrane protein 1 (IFITM1) was downregulated in MPNST tissues compared to those in PN tissues from patients with NF1. Overexpression of IFITM1 in NF1-associated MPNST cells resulted in a significant decrease in Ras activation (GTP-Ras) and downstream extracellular regulatory kinase 1/2 (ERK1/2) phosphorylation, whereas downregulation of IFITM1 via treatment with small interfering RNA in normal Schwann cells had the opposite result, indicating that expression levels of IFITM1 are closely associated with tumor progression in NF1. Treatment of MPNST cells with interferon-gamma (IFN-γ) significantly augmented the expression of IFITM1, thereby leading to a decrease in Ras and ERK1/2 activation. Despite the small number of patient samples, these findings may potentially provide a new target for chemotherapy in patients with NF1-associated MPNSTs. In xenograft mice injected with MPNST cells, IFN-γ treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-γ is a good candidate for the therapeutic treatment of MPNSTs in NF1
Risk Factors for 90-Day Readmission Among Patients with Metastatic Spine Tumors in South Korea: A Nationwide Population-Based Study
No full textBackground: Population-based studies on the cause of readmission within 90 days after surgery or radiotherapy for metastatic spine tumors are scarce. We aimed to investigate the risk factors for readmission within 90 days after initial surgical or radiation treatment for metastatic spine tumors. Methods: Patients who were diagnosed with metastatic spine tumors between 2012 and 2019 and underwent spinal magnetic resonance imaging within 1 year were classified according to treatment (surgical or radiotherapy groups), and the causes of the 90-day readmission and patient characteristics were compared. Results: Overall, data from 15,815 patients (surgical group, 13,974 patients; radiotherapy group, 1841 patients) were evaluated. Radiotherapy was preferred in younger and male patients with a high Charlson Comorbidity Index, whereas surgery was mainly performed in patients with lumbar metastasis. Radiotherapy, age of 30–69 years, male sex, and Charlson Comorbidity Index >1 increased the risk of 90-day readmission in patients with metastatic spine tumors. The main causes of 90-day readmission among patients with metastatic spine tumors who received radiotherapy included tumor recurrence, chemotherapy, radiotherapy, and treatment of other organ metastases with radiotherapy. Conclusions: These study findings offer a better understanding of the causes of readmission following radiotherapy or surgical treatment in patients with metastatic spine tumors, and these results can help reduce postoperative morbidity and medical costs among these patients
Gut microbiome predicts cognitive function and depressive symptoms in late life
Get PDFDepression in older adults with cognitive impairment increases progression to dementia. Microbiota is associated with current mood and cognition, but the extent to which it predicts future symptoms is unknown. In this work, we identified microbial features that reflect current and predict future cognitive and depressive symptoms. Clinical assessments and stool samples were collected from 268 participants with varying cognitive and depressive symptoms. Seventy participants underwent 2-year follow-up. Microbial community diversity, structure, and composition were assessed using high-resolution 16 S rRNA marker gene sequencing. We implemented linear regression to characterize the relationship between microbiome composition, current cognitive impairment, and depressive symptoms. We leveraged elastic net regression to discover features that reflect current or future cognitive function and depressive symptoms. Greater microbial community diversity associated with lower current cognition in the whole sample, and greater depression in participants not on antidepressants. Poor current cognitive function associated with lower relative abundance of Bifidobacterium, while greater GABA degradation associated with greater current depression severity. Future cognitive decline associated with lower cognitive function, lower relative abundance of Intestinibacter, lower glutamate degradation, and higher baseline histamine synthesis. Future increase in depressive symptoms associated with higher baseline depression and anxiety, lower cognitive function, diabetes, lower relative abundance of Bacteroidota, and lower glutamate degradation. Our results suggest cognitive dysfunction and depression are unique states with an overall biological effect detectable through gut microbiota. The microbiome may present a noninvasive readout and prognostic tool for cognitive and psychiatric states
Decreased incidence of peritoneal dialysis-associated peritonitis in young children
Get PDFAim: Peritonitis is the most common complication of peritoneal dialysis (PD). This study aimed to investigate changes in the incidence, risk factors, microbiology, and clinical outcomes of PD-associated peritonitis in the past decades. Methods: This was a retrospective study that included children who initiated chronic PD at our institution between 2000 and 2017. The patients were divided into two groups according to the year of initiation: those who initiated PD between 2000 and 2008 and those who initiated PD between 2009 and 2017. The incidence and characteristics of peritonitis were compared between the groups. Results: A total of 184 patients with a median age of 10.2 years were included in this study. Of the patients, 92 experienced 210 episodes of peritonitis. The incidence rate of peritonitis decreased from 0.35 to 0.21 episodes/patient year during the study period (P = 0.001). During the 2000–2008 period, the 2-year peritonitis-free survival rate was significantly lower for patients under 2 years of age than for the other age groups (P = 0.004), whereas this was not observed during the 2009–2017 period. The multivariable Cox proportional hazard model showed that the <2 years age group had a significantly higher risk of developing peritonitis in the 2000–2008 period. However, this was not evident in the 2009–2017 period. Conclusions: The incidence of PD-associated peritonitis decreased, particularly in children under 2 years of age. Thus, younger age may not be a risk factor for PD-associated peritonitis
Age- and ethnic-driven molecular and clinical disparity of East Asian breast cancers
Get PDFBackground: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive. Methods: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities. Results: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy. Conclusions: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients
Radiation dose during transarterial chemoembolization and associated factors
No full textPurpose: To provide detailed reports on radiation doses during transarterial chemoembolization (TACE) in the cone-beam computed tomography (CBCT) era and to identify the associated factors. Methods: This retrospective study included 385 consecutive patients who underwent initial conventional TACE for hepatocellular carcinoma (HCC) between January 2016 and December 2017. In most cases, CBCT was performed at the common hepatic artery or celiac axis to confirm the location of the tumor and the three-dimensional hepatic artery anatomy. Superselective TACE was performed for all technically feasible cases. Information on total dose area product (DAP), total cumulative air kerma (CAK), fluoroscopy time, and DAP and CAK of each digital subtraction angiography (DSA) and CBCT scan was recorded. Multiple linear regression analysis was performed to identify the factors associated with increased DAP during TACE. Results: The mean values of total DAP and CAK were 165.2 ± 81.2 (Gy·cm²) and 837.1 ± 571.0 (mGy), respectively. The mean fluoroscopy time was 19.1 ± 10.3 min. The mean DAP caused by fluoroscopy, DSA, and CBCT was 51.8 ± 43.9, 28.0 ± 24.1, and 83.9 ± 42.1 Gy·cm², respectively. Male sex, a high body mass index, largest tumor size > 3 cm, presence of aberrant right and left hepatic arteries, and superselective TACE were identified as independent predictors of increased total DAP during TACE. Conclusion: We were able to provide detailed reports on radiation doses during TACE and associated factors
Effect of photobiomodulation and corticopuncture methods on tooth displacement and gene expression: animal study
No full textAim: The aim of this study was to evaluate the expression levels of vascular endothelial growth factor (VEGF), Peroxiredoxin 1 (PRX1), glucose transporter 1 (GLUT1) and type I collagen (COL1) and the rate of tooth movement comparing 3 accelerated tooth movement (ATM) methods: Corticopuncture (CP), photobiomodulation (PBM) and the combined technique (CP + PBM) on days 1, 3, 7 and 14. Methods: Orthodontic tooth movement was induced in 24 male Wistar rats. CP procedure included three perforations: two in the palate and one mesial to the molars. GaAlAs diode laser irradiation was performed on days 0, 2, 4 and 6, totaling 4 irradiations. 14 days (810 nm, 100 mW, 15 s). Gingival tissue was collected from the cervical area of both first molars and qPCR was performed to isolate and quantify mRNA levels. Results: All ATM groups showed increased tooth displacement compared to control after 14 days (20% for PBM; 40% for CP and 60% for CP + PBM). PBM showed higher VEGF expression on days 1,3 and 7 followed by CP and CP + PBM. PRX1 levels increased on days 1 and 3 in PBM and CP + PBM. GLUT1 increased on day 3 in all groups. No difference was found on levels of VEGF, PRX1 and GLUT1 among the groups on day 14, except for COL1 which increased significantly in PBM group. Conclusion: All ATM methods showed higher expression of all of VEGF, PRX1, GLUT1, COL1 than control group. PBM and CP + PBM groups had more expression related to angiogenesis, glucose uptake, oxidative stress and collagen synthesis
Clinical and Angiographic Outcomes of Endovascular Treatment for Acute Intracranial Vertebral Artery Dissecting Aneurysms Using Double-Overlapping Stents: Low-Profile Visualized Intraluminal Support within Enterprise Stents
Get PDFObjective: The use of reconstructive treatment with a double-overlapping stents has proven to be effective and safe in the current treatment of intracranial vertebral artery dissecting aneurysms (VADAs). We employed a combination of overlapping stents, using low-profile visualized intraluminal support (LVIS) within the Enterprise stent. This combination was chosen to minimize the outward bulging of the inner LVIS by overlapping it with the Enterprise stent while maintaining flow diversion and stability. This study aimed to evaluate the clinical and angiographic outcomes following the use of double-overlapping stents with LVIS within the Enterprise stent for the treatment of VADAs. Methods: From March 2016 to January 2022, total 28 patients with unruptured VADAs were treated with the double-overlapping stent technique using LVIS within an Enterprise stent in our institute. The Enterprise stent was deployed first, followed by the LVIS stent. Patient clinical and angiographic characteristics, procedural complications, and follow-up outcomes were retrospectively reviewed. Results: All 28 patients (18 males and 10 females) were successfully treated with double-overlapping stent deployment. There were no procedural complications or new neurological deficits in any patient. Of the 28 patients, four VADAs had posterior inferior cerebellar artery involvement. Procedure-related parent artery occlusion did not occur during the angiographic follow-up conducted 6 to 12 months after the procedure. Out of 28 patients, 24 showed complete healing, three had focal residual stenosis or dilatation with residual sac and only one had a residual dissecting flap with aneurysm. All patients, including the four patients, did not require any additional procedures. The postoperative modified Rankin scale scores were 0–1 for all patients. Conclusion: A double-overlapping stent, with a flow-diversion effect, is a safe and effective treatment for patients with VADAs. In particular, when using the LVIS stent within an Enterprise stent, it minimizes the bulging of the inner LVIS stent while maintaining flow diversion and stability. Therefore, both can be effectively utilized as overlapping stents
Amelioration of Insulin Resistance after Delivery Is Associated with Reduced Risk of Postpartum Diabetes in Women with Gestational Diabetes Mellitus
Get PDFBackground: Identifying risk factors for postpartum type 2 diabetes in women with gestational diabetes mellitus (GDM) is crucial for effective interventions. We examined whether changes in insulin sensitivity after delivery affects the risk of type 2 diabetes in women with GDM. Methods: This prospective cohort study included 347 women with GDM or gestational impaired glucose tolerance, who attended the follow-up visits at 2 months postpartum and annually thereafter. Changes in insulin sensitivity were calculated using the Matsuda index at GDM diagnosis and at 2 months postpartum (ΔMatsuda index). After excluding women with pregestational diabetes or those followed up only once, we analyzed the risk of postpartum type 2 diabetes based on the ΔMatsuda index tertiles. Results: The incidence of type 2 diabetes at the two-month postpartum visit decreased with increasing ΔMatsuda index tertiles (16.4%, 9.5%, and 1.8%, P=0.001). During a 4.1-year follow-up, 26 out of 230 women who attended more than two follow-up visits (11.3%) developed type 2 diabetes. Compared to the lowest tertile, subjects in the highest ΔMatsuda index tertile showed a significantly reduced risk of type 2 diabetes (hazard ratio, 0.33; 95% confidence interval, 0.12 to 0.93; P=0.036) after adjusting for confounders. Conclusion: Improvement in insulin sensitivity after delivery is associated with a reduced risk of postpartum type 2 diabetes in women with GDM. Postpartum changes in insulin sensitivity could be a useful prediction for future type 2 diabetes development in women with GDM
Initial experience of a novel ureteral silicon-covered metallic mesh stent in malignant ureteric obstruction: a single-center retrospective study
No full textBackground: This study aimed to investigate initial experiences and outcomes of a retrograde inserted new silicone-covered metallic ureteric stent (Urexel™) for malignant ureteric obstruction. Methods: We retrospectively reviewed the medical records for 12 consecutive patients who underwent Urexel™ stent placement for malignant ureteric obstruction from March 2020 to March 2021. The Urexel™ stent is a segmental metallic ureteric stent composed of a nitinol mesh covered with a silicone membrane. We evaluated the clinical outcomes and complications of this new metallic ureteric stent. Results: The median age of patients was 61.5 (44–82) years, and the median follow-up was 25.5 (4–37) months. One of the 12 patients underwent bilateral stent insertion, Urexel™ stents were placed in a total of 13 ureteral units. There was no technical failure during stent placement. The median length of obstructions was 9 (1–22) cm. Balloon dilation was necessary in 38.5% (5/13 ureter units) of cases. The 6-month success rate was 83.3%, 1-year success rate was 70%, and estimated success rate was 44.4% at 2-year. Encrustation, migration and hyperplasia were the cause of overall treatment failure in all 6 cases of failure, with median elapsed time to failure of 9.5 (1–30) months. Common complications included persistent pain, acute pyelonephritis, and lower urinary tract symptoms, but they were Clavien-Dindo grade I or II. Conclusions: In this initial series of novel ureteral silicon-covered metallic mesh stents, Urexel™ provided acceptable success and complication rate in malignant ureteric obstructions