Magnetic Resonance Imaging Features for Differentiating Low-Grade and High-Grade Malignant Peripheral Nerve Sheath Tumors.

OBJECTIVE: This study aimed to assess the usefulness of magnetic resonance imaging (MRI) findings for differentiating low-grade and high-grade malignant peripheral nerve sheath tumors (MPNSTs). METHODS: This study included 31 patients (onset age range, 19-83 years; mean onset age, 57 years; 9 men and 22 women) with 36 histopathologically proven MPNSTs (7 low-grade MPNSTs and 29 high-grade MPNSTs) who underwent preoperative MRI between December 2007 and October 2022. Quantitative and qualitative MRI findings were retrospectively evaluated and compared between the 2 subtypes. RESULTS: The maximum tumor diameter (106.1 ± 64.0 vs 54.9 ± 19.8 mm, P = 0.032) and tumor-to-muscle signal intensity ratio (SIR) of fat-suppressed gadolinium-enhanced T1-weighted images (2.69 ± 1.40 vs 1.62 ± 0.40, P = 0.005) were significantly higher in high-grade MPNSTs than in low-grade MPNSTs. The receiver operating characteristic analysis revealed that the tumor-to-muscle SIR of fat-suppressed gadolinium-enhanced T1-weighted images exhibited the highest area under the curve value (0.88), followed by the maximum tumor diameter (0.76). The sensitivity and specificity of the tumor-to-muscle SIR of fat-suppressed gadolinium-enhanced T1-weighted images for diagnosing high-grade MPNST at an optimal SIR threshold of greater than 1.73 were 90% and 83%, respectively. However, other MRI findings showed no significant differences between the 2 subtypes (P = 0.16-1.00). CONCLUSIONS: Although the MRI findings of low-grade and high-grade MPNST overlapped considerably, the maximum tumor diameter and degree of contrast enhancement can be used to differentiate low-grade MPNST from high-grade MPNST.

Association Between Right Ventricular Contractile Function and Cardiac Events in Isolated Postcapillary and Combined Pre- and Postcapillary Pulmonary Hypertension.

BACKGROUND: Recent studies have shown that patients with combined pre- and postcapillary pulmonary hypertension (CpcPH) had worse outcomes than those with isolated postcapillary pulmonary hypertension (IpcPH). However, the prognostic factors including right ventricular (RV) function have not been well documented. The aim of this study was to assess the differentiation of PH phenotypes, using echocardiography, and the association between RV longitudinal strain and cardiac events. METHODS AND RESULTS: We prospectively recruited consecutive patients who had undergone right heart catheterization. The primary endpoint was cardiovascular death or readmission due to heart failure. We included 137 patients with Group 2 PH. A RV longitudinal strain of 17% was sensitive (85%) and specific (70%) to determine the CpcPH. During a median period of 31 months, 43 patients experienced the primary endpoint during follow-up. In a multivariate analysis, RV longitudinal strain was associated with the primary endpoint in both CpcPH and IpcPH (HR: 0.84, P = 0.003; HR: 0.86, P = 0.001). CONCLUSIONS: Lower RV longitudinal strain was independently associated with worse outcomes in CpcPH and IpcPH. RV longitudinal strain may play a prognostic role in PH phenotypes.

Association between Sarcopenia/Lower Muscle Mass and Short-Term Regression of Deep Vein Thrombosis Using Direct Oral Anticoagulants.

Advanced age, obesity, and muscle weakness are independent factors in the onset of deep vein thrombosis (DVT). Recently, an association between sarcopenia and DVT has been reported. We hypothesized that sarcopenia related factors, observed by ultrasonography, are associated with the regression effect on the thrombus following anticoagulation therapy. The present study focused on gastrocnemius muscle (GCM) thickness and the GCM's internal echogenic brightness. We examined the association with DVT regression following direct oral anticoagulants (DOACs) treatment.The prospective cohort study period was between October 2017 and August 2018. We enrolled 46 patients diagnosed with DVT by ultrasonography, who were aged >60 years old and treated with DOACs. Sarcopenia was evaluated using the Asian Working Group for Sarcopenia flowchart. The average DOACs treatment period was 94 days, and 29 patients exhibited thrombus regression. On univariate logistic regression analysis, sarcopenia, average GCM diameter index, and gastrocnemius integrated backscatter index were significantly associated with thrombus regression. In a multivariate model, only the average GCM diameter index correlated with thrombus regression.The average GCM diameter index is associated with DVT regression treated with DOACs. Considering the GCM diameter during DVT treatment can be a marker to make a decision for the treatment of DVT.

Comparison of image quality and pancreatic ductal adenocarcinoma conspicuity between the low-kVp and dual-energy CT reconstructed with deep-learning image reconstruction algorithm.

PURPOSE: To compare the image quality and conspicuity of pancreatic ductal adenocarcinoma (PDAC) between the low-kVp and dual-energy pancreatic protocol CT reconstructed with deep-learning image reconstruction (DLIR). METHOD: A cohort of 111 consecutive patients (median age, 72 years; 56 men) undergoing a pancreatic protocol CT were retrospectively analyzed. Among them, 58 patients underwent 80-kVp CT (80-kVp group), and 53 patients underwent dual-energy CT and reconstructed at 40-keV (40-keV group). The medium-strength level of DLIR were used in both groups. Quantitative measurements, qualitative image quality, PDAC conspicuity, and dose-length product (DLP) were compared between the two groups using Mann-Whitney U test. RESULTS: A total of 20 and 16 PDACs were found in the 80-kVp and 40-keV groups, respectively. CT numbers of the vasculatures and parenchymal organs (P <.001 for all) and the background noise at both pancreatic and portal venous phases (P <.001) were higher in the 40-keV group than in the 80-kVp group. The signal-to-noise ratio (SNR) of all anatomical structures (P <.001-0.005), except for the liver in reviewer 2 (P =.47), and the tumor-to-pancreas contrast-to-noise ratio (CNR; P <.001-0.01) were higher in the 40-keV group than in the 80-kVp group. No difference was found in the image quality at both phases (P =.30-0.90). PDAC conspicuity was better in the 40-keV group than in the 80-kVp group (P =.007-0.03). DLP at pancreatic (275 vs. 313 mGy*cm; P =.05) and portal venous phases (743 vs. 766 mGy*cm; P =.20) was comparable between the two groups. CONCLUSION: Under the same DLP, virtual monoenergetic images at 40-keV demonstrated higher SNR and tumor-to-pancreas CNR and better PDAC conspicuity compared to the 80-kVp setting.

Possible involvement of hypothalamic nucleobindin-2 in hyperphagic feeding in Tsumura Suzuki obese diabetes mice.

The aim of this study was to clarify the hypothalamic neuropeptides that are associated with hyperphagic feeding in Tsumura Suzuki Obese Diabetes (TSOD) mice, a model of type 2 diabetes with polygenic abnormalities. TSOD mice showed an increase in body weight and hyperleptinemia from 1 month of age and hyperphagic feeding, hyperglycemia, hyperlipidemia and hyperinsulinemia from 3 to 12 months of age compared with age-matched non-diabetic control Tsumura Suzuki Non Obesity (TSNO) mice. The mRNA level of nucleobindin-2 (NUCB2), the precursor of the anorexigenic neuropeptide nesfatin-1, was significantly decreased in the hypothalamus of TSOD mice compared with that in TSNO mice from 3 to 12 months of age. The protein level of NUCB2 was significantly decreased in the hypothalamus of TSOD mice compared with that in TSNO mice at 3 months of age. The mRNA levels of galanin, melanin-concentrating hormone, neuropeptide Y, and pro-opiomelanocortin were significantly changed in the hypothalamus in TSOD mice at several time points. Another model of type 2 diabetes, db/db mice, which is a mutant mouse that lacks a functional leptin receptor, showed hyperphagic feeding but no change in hypothalamic NUCB2 mRNA compared with non-diabetic control db/+ mice. The results suggest that the disrupted control of hypothalamic NUCB2-mediated signaling may contribute to hyperphagic feeding in TSOD mice. In addition, the mechanism for the development of hyperphagic feeding in TSOD mice is different than that in db/db mice.

"Accelerated aging" of the heart as heart failure with preserved ejection fraction-analysis using leg-positive pressure stress echocardiography.

The aging process is a significant risk factor for heart failure. The incidence of heart failure with preserved ejection fraction (HFpEF) dramatically increases with age. Although HFpEF occurs along a continuum of aging of the cardiovascular system, the pathophysiology that differentiates overt HFpEF from physiological aging is not fully understood. A total of 102 subjects were prospectively recruited: 25 patients with HFpEF and 77 healthy controls. Controls were stratified into three age-groups: young (n = 27, 20-40 years), middle aged (n = 25, 40-65 years), and elderly (n = 25, > 65 years). All participants underwent preload stress echocardiography using a leg-positive pressure (LPP) maneuver. With an increase in age, progressive concentric left ventricular (LV) remodeling was observed in healthy controls, resulting in the hemodynamic consequences of an age-dependent increase in the E/e' ratio (ANOVA, P < 0.001). During LPP stress, the E/e' ratio significantly increased in the middle-aged and elderly groups (from 8 ± 2 to 9 ± 3, from 10 ± 2 to 12 ± 3, P < 0.05, respectively), and this was more pronounced in patients with HFpEF (from 16 ± 5 to 17 ± 7, P < 0.05). Forward stroke volume (SV) significantly increased in each healthy group during LPP stress (all P < 0.001) but failed to increase in the HFpEF group (from 43 ± 13 to 44 ± 14 mL/m2, P = 0.65). In a multivariate analysis, LV mass index (odds ratio [OR] 1.051, P < 0.05), E/e' ratio (OR 1.480; P < 0.05), and change in SV (OR 0.780; P < 0.05) were independent parameters that differentiated HFpEF from physiological aging. Structural remodeling and impaired preload reserve may both be critical features that characterize the pathophysiology of HFpEF.

Deleterious Effects of Epicardial Adipose Tissue Volume on Global Longitudinal Strain in Patients With Preserved Left Ventricular Ejection Fraction.

Background: It is known that epicardial adipose tissue (EAT) volume is linked to cardiac dysfunction. However, it is unclear whether EAT volume (EATV) is closely linked to abnormal LV strain. We examined the relationship between EATV and global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) in patients with preserved LV function. Methods: Notably, 180 consecutive subjects (68 ± 12 years; 53% men) underwent 320-slice multi-detector computed tomography coronary angiography and were segregated into coronary artery disease (CAD) (≥1 coronary artery branch stenosis ≥50%) and non-CAD groups. GLS, GCS, and GRS were evaluated by 2-dimensional speckle tracking in patients with preserved left ventricular (LV) ejection fraction (LVEF) ≥50%. Results: First, GLS, but not GRS and GCS, was lower in the high EATV group though the LVEF was comparable to the low EATV group. Frequency of GLS ≤18 was higher in the high EATV group. Second, multiple regression model showed that EATV, age, male sex, and CAD, were determinants of GLS. Third, the cutoff points of EATV were comparable (~116-117 mL) in both groups. The cutoff of EATV ≥116 showed a significant correlation with GLS ≤18 in overall subjects. Conclusions: Increasing EATV was independently associated with global longitudinal strain despite the preserved LVEF and lacking obstructive CAD. Our findings suggest an additional role of EAT on myocardial systolic function by impaired LV longitudinal strain.

Deterioration of biventricular strain is an early marker of cardiac involvement in confirmed sarcoidosis.

AIMS: Risk assessment of developing cardiac involvement in systemic sarcoidosis can be challenging because of limited data. Recently, attention has been given to left ventricular and right ventricular (LV and RV) involvement in cardiac sarcoidosis (CS) and its prevalence, relevance, and prognostic value. The aim of this study was to assess the role of biventricular strain to predict prognosis in confirmed sarcoidosis patients. METHODS AND RESULTS: LV and RV longitudinal strains (LSs) were evaluated by 2D speckle tracking in 139 consecutive confirmed sarcoidosis patients without other pre-existing structural heart diseases, and 52 age- and gender-matched control subjects. The primary endpoint was CS-related events (cardiac death or development of cardiac involvement). Sarcoidosis without cardiac involvement had significantly lower LV and RV free wall LS compared with control subjects. Basal LS had a higher area under the curve for differentiation of sarcoidosis in patients without cardiac involvement compared to control (cut-off value: -18% with 89% sensitivity and 69% specificity). During a median period of 50 months, the occurrence of CS-related events was observed in 20 patients. In a multivariate analysis, basal LV LS and RV free wall LS were associated with the events [hazard ratio (HR) 0.72, P < 0.001 and HR: 0.83, P = 0.006, respectively]. Patients with impaired biventricular function had significantly shorter event-free survival than those with preserved biventricular function (P < 0.001). CONCLUSION: Deterioration of biventricular strain was associated with CS-related events. This information might be useful for clinical evaluation and follow-up in sarcoidosis.

Updated Left Ventricular Diastolic Function Recommendations and Cardiovascular Events in Patients with Heart Failure Hospitalization.

BACKGROUND: Evaluation of diastolic dysfunction is crucial in determining elevated left atrial pressure. However, a validation of the long-term prognostic value of the newly proposed algorithm updated in 2016 has not been performed. The aim of the present study was to investigate the relative value of the updated 2016 diastolic dysfunction grading system for the incidence of readmission in patients with heart failure (HF) with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). METHODS: Two hundred thirty-two patients hospitalized with HF were retrospectively evaluated. Subjects were divided into two subgroups: those with HFrEF (n = 127) and those with HFpEF (n = 105). Readmission risk scores were calculated using the Yale Center for Outcomes Research and Evaluation HF, LACE index, and HOSPITAL scores. The primary end point was readmission following HF and cardiac death. RESULTS: Over a period of 24 months, 86 patients were either readmitted or died. Multivariate Cox analysis was performed on both the HFrEF and HFpEF groups. In the HFrEF group, both the 2009 and 2016 algorithms had superior incremental value for the association of the primary end point to several readmission risk scores. In the HFpEF group, only the 2016 algorithm led to significant improvement in association with the primary end point. The 2016 algorithm had incremental value over several readmission risk scores alone. CONCLUSIONS: The recommendations of the 2016 algorithm can be useful for readmission and cardiac mortality risk assessment in patients with HFrEF and HFpEF. The use of echocardiography to estimate elevated left atrial pressure appears to identify a higher risk group and may allow a more tailored approach to therapy.

Higher CHADS2 score is associated with impaired coronary flow reserve: A study using phase contrast cine magnetic resonance imaging.

BACKGROUND: The presence of coronary microvascular dysfunction (CMD) is an important prognostic marker for coronary artery disease (CAD) patients. The purpose of this study was to investigate whether the CHADS2 score is associated with CMD evaluated by magnetic resonance imaging (MRI). MATERIALS AND METHODS: One hundred forty three patients with known or suspected CAD (mean age 70.3±9.5years) were enrolled. All patients did not have any significant coronary stenosis on X-ray coronary angiography (CAG) at the time of MRI acquisition. By using a 1.5T MRI scanner, breath-hold phase contrast cine MRI images of coronary sinus (CS) were obtained to assess the blood flow of CS both at rest and during adenosine triphosphate (ATP) infusion. Coronary flow reserve (CFR) was calculated as CS blood flow during ATP infusion divided by CS blood flow at rest. CMD was defined as CFR<2.5 according to a previous study. Patients were allocated to four groups based on the CHADS2 score (group1: CHADS2 score=0, group2: CHADS2 score=1; group3: CHADS2 score=2, and group4: CHADS2 score≥3). RESULTS: Mean CFR was 2.81±0.95 (77.6±32.7mL/min at rest; 208.2±86.5mL/min during ATP infusion, p<0.001). Patients with higher CHAD2 score had lower CFR. In the multiple logistic regression analysis, CHADS2 score was independently associated with CFR (odds ratio=0.61, 95% confidence interval: 0.37-0.99, p=0.049). CONCLUSIONS: Higher CHADS2 score was significantly associated with lower CFR evaluated by phase contrast cine MRI.

Oral administration of corn zein hydrolysate stimulates GLP-1 and GIP secretion and improves glucose tolerance in male normal rats and Goto-Kakizaki rats.

We have previously demonstrated that ileal administration of the dietary protein hydrolysate prepared from corn zein (ZeinH) stimulated glucagon-like peptide-1 (GLP-1) secretion and attenuated hyperglycemia in rats. In this study, to examine whether oral administration of ZeinH improves glucose tolerance by stimulating GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion, glucose tolerance tests were performed in normal Sprague-Dawley male rats and diabetic Goto-Kakizaki (GK) male rats. The test solution was gavaged before ip glucose injection in normal rats or gavaged together with glucose in GK rats. Blood samples were collected from the tail vein or by using the jugular catheter to measure glucose, insulin, GLP-1, and GIP levels. In the ip glucose tolerance test, oral administration of ZeinH (2 g/kg) significantly suppressed the glycemic response accompanied by an immediate increase in plasma GLP-1 and GIP levels in normal rats. In contrast, oral administration of another dietary peptide, meat hydrolysate, did not elicit a similar effect. The glucose-lowering effect of ZeinH was attenuated by a GLP-1 receptor antagonist or by a GIP receptor antagonist. Furthermore, oral ZeinH induced GLP-1 secretion and reduced glycemic response in GK rats under the oral glucose tolerance test. These results indicate that the oral administration of the dietary peptide ZeinH improves glucose tolerance in normal and diabetic rats by its incretin-releasing activity, namely, the incretinotropic effect.

Low-dose glucocorticoid therapy complements the pituitary-adrenocortical system and reduces anxiety and insomnia in myasthenia gravis patients.

Myasthenia gravis (MG) is an autoimmune disorder generally mediated by antibodies against the acetylcholine receptors of the skeletal muscles. Depending on the disease burden, MG patients may experience chronic dysregulation of both the hormonal stress axis and the immune system, consequently, aggravating the disease itself but also leading to secondary psychopathological abnormalities. A long-term clinical course requires long-term glucocorticoid (GC) therapy, which may change the psychological state by affecting the pituitary-adrenocortical system in MG patients. In this study, we investigated the function of the pituitary-adrenocortical system in MG patients who were treated with prednisolone (PSL) and evaluated their quality of life by using the Medical Outcomes Study 36-item Short-Form Health Survey and the 28-item general health questionnaire (GHQ-28). ACTH and cortisol levels in the plasma of patients who were treated with PSL (PSL[+] group, n = 18) were lower than those in the plasma of patients who were treated without PSL (PSL[-] group, n = 29; P < 0.05 and P < 0.01, respectively). In the PSL(+) group, we confirmed that cortisol levels negatively correlated with daily PSL dosages (P < 0.05). The anxiety and depression scores from the GHQ-28 in the PSL(+) group were lower than those in the PSL(-) group (P < 0.05, respectively). There was no significant correlation between cortisol levels and corticotropin levels in plasma of the PSL(-) group. However, we confirmed that corticotropin levels positively correlated with cortisol levels in plasma (P < 0.01) and negatively correlated with anxiety/insomnia scores from the GHQ-28 (P < 0.05) in the PSL(+) group. In conclusion, low-dose GC treatment complemented the pituitary-adrenocortical system and improved the psychological state in MG patients.

Clinical implications of the type 1/type 2 balance of helper T cells and P-glycoprotein function in peripheral T lymphocytes of myasthenia gravis patients.

Myasthenia gravis is an autoimmune disorder mediated by antibodies against the acetylcholine receptors of the skeletal muscles. Imbalances between T helper type 1 and type 2 cytokine production play a key role in the induction and development of several autoimmune diseases. Peripheral T helper type 1 and type 2 cells in 50 myasthenia gravis patients were estimated by intracellular cytokines. The percentage of T helper type 1 cells in CD4(+) cells was higher than that of type 2 or type 0 cells (P<0.0001). There was a significant correlation between T helper type 1/type 2 ratio and the P-glycoprotein function on CD3(+) T cells (P=0.008). In the patients treated with prednisolone alone (n=12), there was a significant correlation negatively between the percentage of change in the T helper type 1/type 2 ratio and the reduction rate of quantitative myasthenia gravis scores after 12 months of treatment (P=0.012). In contrast, all of the patients treated with prednisolone and calcineurin inhibitor in combination saw reductions in the scores. Our data suggest that the T helper type 1/type 2 ratio was involved in the disease activity of the patients treated with prednisolone alone. On the other hand, the patients treated with prednisolone and calcineurin inhibitor in combination had their disease condition improved regardless of the T helper type 1 predominance. Therefore, the data suggest that supplemental calcineurin inhibitors are effective for the myasthenia gravis patients treated with prednisolone alone when their T helper balance shifts toward to type 1.

Clinical implication of peripheral CD4+CD25+ regulatory T cells and Th17 cells in myasthenia gravis patients.

Myasthenia gravis (MG) is an autoimmune disorder generally mediated by antibodies against the acetylcholine receptors (AChR) of the skeletal muscles. CD4 T cells help B cells to produce antibodies through their production of cytokines or chemokines. In this study, we evaluated the frequency of regulatory (Treg) and IL-17 producing CD4 T-cell subsets (Th17) in peripheral blood mononuclear cells (PBMCs) of patients with MG. The transcription factor, forkhead transcription factor (Foxp3), is essential for T-cell regulatory function, and the orphan nuclear receptor, RORgammaT, is important in Th17 cell differentiation. In MG patients, Foxp3 mRNA expression in PBMCs was lower than those in healthy subjects (p=0.007), while there was no significant difference of RORgammaT mRNA expression between MG patients and healthy subjects. Glucocorticoid-induced tumour-necrosis-factor receptor-related protein (GITR) is expressed predominantly on CD4(+)CD25(+) Treg cells. We found that the number of GITR(+)CD4(+)CD25(+) T cells in peripheral lymphocytes in MG patients was lower than that in healthy subjects (P<0.01). In addition, there was a significant positive correlation between the change of the frequency of GITR(+)CD4(+)CD25(+) T cells and the changing rate in quantitative myasthenia gravis scores (%) (p=0.03). Furthermore, there was a significant negative correlation between the change of the percentage of GITR(+)CD4(+)CD25(+) T cells (% lymphocytes) and the changing rate of daily PSL doses (%) (P=0.002). The relative RORgammaT levels in PBMCs negatively correlated with the Th1/Th2 ratio in CD4(+) cells in MG patients (p=0.014). In conclusion, our findings suggest that Th17 cells affect the production of autoantibodies through their influence on the Th1- and Th2-cytokine balance in PBMCs of MG patients. On the other hand, Treg cells are suggested to be involved in the clinical condition or severity of MG disease.