Improvement of muscle quality assessed using the phase angle is influenced by recovery of knee extension strength in patients with hip fractures.

BACKGROUND AND AIMS: Studies reported that knee extension strength on the operated side in patients with hip fractures was not recovered to the level on the non-operated side 6 months after surgery or later. In a cross-sectional study, we revealed that a reduction in isometric knee extension muscle strength on the operated side in patients with hip fractures approximately 6 months after surgery was associated with not only a reduction in skeletal muscle mass but also a reduction in muscle quality, characterized by a reduction in the phase angle (PhA). Furthermore, the mechanisms of knee extension strength improvement can be clarified in more detail using the minimal significant change as the index of recovery. However, no longitudinal studies have examined the factors for knee extension strength improvement based on the minimal significant change in patients with hip fractures 6 months after surgery. This study aimed to longitudinally examine the factors influencing the recovery of knee extension strength based on the minimal significant change in patients with hip fractures between 2 weeks and approximately 6 months after surgery. METHODS: In this study, the outcomes used were basic and medical information, PhA, skeletal muscle index (SMI), pain, one-leg standing time, movement control during one-leg standing, and walking speed. For PhA, SMI, pain, one-leg standing time, movement control during one-leg standing, and walking speed, the amount of change was calculated by subtracting the data at 2 weeks from the data at 6 months. Group classification was determined by dividing the patients into two groups using a previous study as a reference: recovery group if the knee extension strength value approximately 6 months after surgery minus that 2 weeks after surgery was ≥3.3 kgf and non-recovery group if the value was <3.3 kgf. Logistic regression analysis was performed to explore the association between the recovery and non-recovery groups. RESULTS: The recovery group contained 55 patients, while the non-recovery group comprised 35 patients. The only significant factor associated with knee extension muscle strength in the recovery group was the amount of change in PhA. The odds ratio for the amount of change in PhA was 2.26. The discrimination rate of the model was 62.5%. CONCLUSIONS: Our results suggest that recovery of knee extension strength in patients with hip fractures after surgery was mainly because of improvements in muscle quality, not improvements in muscle mass or pain.

Usefulness of pituitary high-resolution 3D MRI with deep-learning-based reconstruction for perioperative evaluation of pituitary adenomas.

PURPOSE: To evaluate the diagnostic value of T1-weighted 3D fast spin-echo sequence (CUBE) with deep learning-based reconstruction (DLR) for depiction of pituitary adenoma and parasellar regions on contrast-enhanced MRI. METHODS: We evaluated 24 patients with pituitary adenoma or residual tumor using CUBE with and without DLR, 1-mm slice thickness 2D T1WI (1-mm 2D T1WI) with DLR, and 3D spoiled gradient echo sequence (SPGR) as contrast-enhanced MRI. Depiction scores of pituitary adenoma and parasellar regions were assigned by two neuroradiologists, and contrast-to-noise ratio (CNR) was calculated. RESULTS: CUBE with DLR showed significantly higher scores for depicting pituitary adenoma or residual tumor compared to CUBE without DLR, 1-mm 2D T1WI with DLR, and SPGR (p < 0.01). The depiction score for delineation of the boundary between adenoma and the cavernous sinus was higher for CUBE with DLR than for 1-mm 2D T1WI with DLR (p = 0.01), but the difference was not significant when compared to SPGR (p = 0.20). CUBE with DLR had better interobserver agreement for evaluating adenomas than 1-mm 2D T1WI with DLR (Kappa values, 0.75 vs. 0.41). The CNR of the adenoma to the brain parenchyma increased to a ratio of 3.6 (obtained by dividing 13.7, CNR of CUBE with DLR, by 3.8, that without DLR, p < 0.01). CUBE with DLR had a significantly higher CNR than SPGR, but not 1-mm 2D T1WI with DLR. CONCLUSION: On the contrast-enhanced MRI, compared to CUBE without DLR, 1-mm 2D T1WI with DLR and SPGR, CUBE with DLR improves the depiction of pituitary adenoma and parasellar regions.

A novel catheter ablation strategy for non-paroxysmal atrial fibrillation combining cryoballoon, radiofrequency, and Marshall-vein ethanol ablations.

BACKGROUNDS: Catheter ablation for non-paroxysmal atrial fibrillation (non-PAF) remains challenging and more effective strategy has been required to reduce postoperative arrhythmia recurrences. This study aims to investigate the efficacy and safety of a novel extensive ablation strategy for non-PAF, that is based on a combination of cryoballoon (CBA), radiofrequency (RFA), and Marshall-vein ethanol ablations (EA-VOM). METHODS: The study was a single-center, retrospective observational study. We enrolled 171 consecutive patients who underwent de-novo catheter ablation for non-PAF under conscious sedation with a novel extensive ablation strategy that included CBA for pulmonary vein isolation (PVI) and left atrial roof ablation (LARA), RFA for mitral isthmus (MI) ablation, superior vena cava isolation, and other linear ablations and EA-VOM. Recurrence of atrial arrhythmias over 1 year, procedure outcomes, and procedure-related complications were investigated. RESULTS: A total of 139 (81.3%) patients remained in sinus rhythm during 1-year follow-up. Of the 139 patients, 51 patients (29.8%) received antiarrhythmic drugs. The mean procedure time was 204 ± 45 min. PVI and LARA ablation by CBA and MI block by RFA and EA-VOM were completed in 171 (100%) and 166 (97.1%) patients, respectively. No serious procedure-related complications were observed except for one case of delayed pericardial effusion. CONCLUSION: Approximately 80% of the study patients were AF-free during 1-year follow-up period after a single procedure based on the novel extensive ablation strategy combining CBA, RFA, and EA-VOM. This strategy for non-PAF may be preferred in terms of maintenance of sinus rhythm, safety even in high-risk patients, and relatively short procedure time.

Association of prediabetes with reduced brain volume in a general elderly Japanese population.

OBJECTIVES: Diabetes frequently results in cognitive impairment, but it is less clear if brain health is adversely affected during the prediabetic stage. Our aim is to identify possible changes in brain volume as measured by magnetic resonance imaging (MRI) in a large elderly population stratified according to level of "dysglycemia." METHODS: This is a cross-sectional study of 2144 participants (median age 69 years, 60.9% female) who underwent 3-T brain MRI. Participants were divided into 4 dysglycemia groups based on HbA1c levels (%): normal glucose metabolism (NGM) (< 5.7%), prediabetes (5.7 to < 6.5%), undiagnosed diabetes (6.5% or higher), and known diabetes (defined by self-report). RESULTS: Of the 2144 participants, 982 had NGM, 845 prediabetes, 61 undiagnosed diabetes, and 256 known diabetes. After adjustment for age, sex, education, body weight, cognitive status, smoking, drinking, and disease history, total gray matter volume was significantly lower among participants with prediabetes (0.41% lower, standardized ß = - 0.0021 [95% CI - 0.0039, - 0.00039], p = 0.016), undiagnosed diabetes (1.4% lower, standardized ß = - 0.0069 [95% CI - 0.012, - 0.002], p = 0.005), and known diabetes (1.1% lower, standardized ß = - 0.0055 [95% CI - 0.0081, - 0.0029], p < 0.001) compared to the NGM group. After adjustment, total white matter volume and hippocampal volume did not differ significantly between the NGM group and either the prediabetes group or the diabetes group. CONCLUSION: Sustained hyperglycemia may have deleterious effects on gray matter integrity even prior to the onset of clinical diabetes. KEY POINTS: • Sustained hyperglycemia has deleterious effects on gray matter integrity even prior to the onset of clinical diabetes.

Genetic Structure of the Liriope muscari Polyploid Complex and the Possibility of Its Genetic Disturbance in Japan.

Anthropogenic activities, such as the movement of plants through greening, can result in genetic disturbance that can interfere with local adaptation in wild populations. Although research is underway to prevent genetic disturbance associated with greening, genetic disturbance of intraspecific polyploidy, which is estimated to be present in 24% of vascular plants, has not been well studied. Liriope muscari is a polyploid complex with known diploid (2n = 36), tetraploid (2n = 72), and hexaploid (2n = 108) forms. The plants of this species tolerate dry and hot conditions and are therefore frequently used for greening and gardening. However, the distribution of this polyploid in Japan, its genetic structure, and genetic disturbance are not known. In this study, we investigated the polyploidy distribution and genetic structure in naturally distributed L. muscari in Japan using chloroplast DNA (cpDNA) haplotypes and nuclear DNA (nDNA). Commercially produced individuals were also studied and compared with natural populations to assess any genetic disturbance of the ploidy complex in this species. Chromosome counts, cpDNA, and nDNA results showed three genetically and cytologically distinct groups in Japan: first, a tetraploid group in mainland Japan; second, a hexaploid group in the Ryukyu Islands; and third, a diploid and tetraploid group in the Ryukyu Islands. Significant isolation by distance was also detected within the three groups (p = 0.001). Genetic disturbance due to greening and gardening should be avoided among the three groups. Genetic disturbance can be reduced by using individuals derived from natural populations that are close to the sites used for greening and gardening. For commercially produced individuals, genetic disturbance is unlikely in the Kanto region, an area of high usage, while genetic disturbance is thought possible in the Ryukyu Islands.

Movement control during one-leg standing is important for the bone mineral density maintenance or improvement.

INTRODUCTION: Both hip fracture and bone mineral density (BMD) decline on the non-fractured side are more likely to occur within 1 year. However, there are no longitudinal study reports on the factors associated with BMD maintenance or improvement within the first year after hip fracture. This study aimed to investigate the factors influencing the neck BMD maintenance or improvement in patients with hip fractures from within 2 weeks-6 months after surgery. MATERIALS AND METHODS: Patients were hip fracture after surgery and were divided into two groups: Among neck BMD changes (6 months minus 2 weeks after surgery) were calculated. Based on among neck BMD change, patients were classified into the BMD maintenance or improvement (change ≥ 0) and the BMD decrease groups (change < 0). Propensity score matching was performed to adjust for confounding factors. To predict the factors affecting neck BMD, hierarchical logistic regression analysis was performed. The dependent variable was the BMD maintenance or improvement group and the BMD decrease group. The independent variables were basic and medical information, and physical functions. RESULTS: The hierarchical logistic regression analysis results showed that movement control during one-leg standing affected femoral neck BMD independently from age, sex. The odds ratio for movement control during one-leg standing was 8.22. The discrimination rate of the model was 69.7%. CONCLUSION: This study suggested that adequate movement control during one-leg standing is important to maintain or improve neck BMD.

Case Report: Importance of MRI Examination in the Diagnosis and Evaluation of COVID-19 mRNA Vaccination Induced Myocarditis: Our Experience and Literature Review.

Acute myocarditis is a rare but serious complication associated with mRNA-based coronavirus disease 2019 (COVID-19) vaccination. In this article, four COVID-19 mRNA vaccination induced myocarditis cases managed at our tertiary Medical Center have been discussed. Three patients had typical myocarditis. One patient suffered from atrioventricular block and heart failure, which required more intensive treatment, but eventually improved. Additionally, a review of cardiac magnetic resonance imaging (MRI) features related to the diagnosis of myocarditis showed that COVID-19 mRNA vaccine-associated myocarditis tend to have more late-gadolinium enhancement (LGE) accumulation in the inferior lateral wall direction. According to a report by the U.S. Centers for Disease Control and Prevention (CDC), the diagnosis of COVID-19 mRNA vaccine-associated myocarditis is based on clinical symptoms, altered myocardial enzymes, cardiac MRI finding, or histopathology. Cardiac MRI is relatively less invasive than myocardial biopsy and plays an important role in the diagnosis of myocarditis. This review may aid in the diagnosis of COVID-19 mRNA vaccine-associated myocarditis.

Generation of Caco-2 cells stably expressing CYP3A4·POR·UGT1A1 and CYP3A4·POR·UGT1A1*6 using a PITCh system.

The small intestine plays a critical role in the absorption and metabolism of orally administered drugs. Therefore, a model capable of evaluating drug absorption and metabolism in the small intestine would be useful for drug discovery. Patients with genotype UGT1A1*6 (exon 1, 211G > A) treated with the antineoplastic drug SN-38 have been reported to exhibit decreased glucuronide conjugation and increased incidence of intestinal toxicity and its severe side effects, including severe diarrhea. To ensure the safety of drugs, we must develop a drug metabolism and toxicity evaluation model which considers UGT1A1*6. In this study, we generated CYP3A4·POR·UGT1A1 KI- and CYP3A4·POR·UGT1A1*6 KI-Caco-2 cells for pharmaceutical research using a PITCh system. The CYP3A4·POR·UGT1A1 KI-Caco-2 cells were shown to express functional CYP3A4 and UGT1A1. The CYP3A4·POR·UGT1A1*6 KI-Caco-2 cells were sensitive to SN-38-induced intestinal toxicity. We thus succeeded in generating CYP3A4·POR·UGT1A1 KI- and CYP3A4·POR·UGT1A1*6 KI-Caco-2 cells, which can be used in pharmaceutical research. We also developed an intestinal epithelial cell model of patients with UGT1A1*6 and showed that it was useful as a tool for drug discovery.

Effectiveness and Safety of Direct Oral Anticoagulants vs. Warfarin and Recurrence After Discontinuation in Patients With Acute Venous Thromboembolism in the Real World.

BACKGROUND: The efficacy of direct oral anticoagulants (DOACs) compared with warfarin for the treatment of venous thromboembolism (VTE), and the recurrence of VTE after discontinuation of anticoagulation therapy in research are limited.Methods and Results: This retrospective study enrolled 893 patients with acute VTE between 2011 and 2019. The cohort was divided into the transient risk, unprovoked, continued cancer treatment, and cancer remission groups. The following were compared between DOACs and warfarin: composite outcome of all-cause death, VTE recurrence, bleeding and composite outcome of VTE-related death, recurrence and bleeding. In the continued cancer treatment group, more bleeding was seen in warfarin-treated patients than in patients treated with DOACs (53.2% vs. 31.2%, [P=0.048]). In addition, composite outcome of VTE-related death and recurrence after discontinuation of anticoagulation therapy (n=369) was evaluated. The continued cancer treatment group (multivariate analysis: HR: 3.62, 95% CI: 1.84-7.12, P<0.005) and bleeding-related discontinuation of therapy (HR: 2.60, 95% CI: 1.32-5.13, P=0.006) were independent predictors of the event after discontinuation of anticoagulation therapy. VTE recurrence after discontinuation of anticoagulation therapy in the cancer remission group was 1.6% and a statistically similar occurrence was found in the transient risk group (12.4%) (P=0.754). CONCLUSIONS: DOACs may decrease bleeding incidence in patients continuing to receive cancer treatment. In patients with bleeding-related discontinuation of anticoagulation therapy, VTE recurrence may increase. Discontinuation of anticoagulant therapy might be a treatment option in patients who have completed their cancer treatment.

Multiple mycotic aneurysms with infective endocarditis: A case report.

Mycotic aneurysms are sometimes seen in patients with infective endocarditis. We report a case of infective endocarditis with multiple mycotic aneurysms. Although antibiotics were effective, mycotic aneurysms appeared in the cerebral, hepatic, and gastroepiploic arteries. A 55-year-old man presented with mitral valve endocarditis due to Streptococcus oralis. Surgical treatment was deferred because of cerebral hemorrhage. After antibiotic initiation, his fever and C-reactive protein levels declined, and blood culture was negative. However, he experienced repeated cerebral hemorrhage and the number of cerebral mycotic aneurysms increased. Additionally, his spleen ruptured and the number of mycotic aneurysms in the hepatic and gastroepiploic arteries increased. After embolization for mycotic aneurysm and mitral valve replacement, no mycotic aneurysms appeared. Regardless of whether laboratory data improve or not, multiple mycotic aneurysms sometimes appear, and cardiac surgery for infection control should be considered in the early phase.

Geriatric nutritional risk index as a predictor of arrhythmia recurrence after catheter ablation of atrial fibrillation.

BACKGROUND AND AIMS: The nutritional risk of patients who undergo atrial fibrillation (AF) ablation varies. Its impact on the recurrence after ablation is unclear. We sought to evaluate the relationship between the nutritional risk and arrhythmia recurrence in patients who undergo AF ablation. METHODS AND RESULTS: We enrolled 538 patients (median 67 years, 69.9% male) who underwent their first AF ablation. Their nutritional risk was evaluated using the pre-procedural geriatric nutritional risk index (GNRI), and the patients were classified into two groups: No-nutritional risk (GNRI â‰§ 98) and Nutritional risk (GNRI < 98). The primary endpoint was a recurrence of an arrhythmia, and its relationship to the nutritional risk was evaluated. We used propensity-score matching to adjust for differences between patients with a GNRI-based nutritional risk and those without a nutritional risk. A nutritional risk was found in 10.6% of the patients, whereas the remaining 89.4% had no-nutritional risk. During a mean follow-up of 422 days, 91 patients experienced arrhythmia recurrences. The patients with a nutritional risk had a significantly higher arrhythmia recurrence rate both in the entire study cohort (Log-rank p = 0.001) and propensity-matched cohort (Log-rank p = 0.006). In a Cox proportional hazard analysis, the nutritional risk independently predicted arrhythmia recurrences in the entire study cohort (hazard ratio [HR]: 3.91, 95% confidence interval [CI]: 1.84-8.35, p < 0.001) and propensity-matched cohort (HR: 6.49, 95% CI: 1.42-29.8, p = 0.016). CONCLUSION: A pre-procedural malnutrition risk was significantly associated with increased arrhythmia recurrences in patients who underwent AF ablation.

Safety and activity of trifluridine/tipiracil and ramucirumab in previously treated advanced gastric cancer: an open-label, single-arm, phase 2 trial.

BACKGROUND: Findings of preclinical and clinical trials in colorectal cancer have shown promising antitumour effects of the co-formulation trifluridine/tipiracil and VEGF inhibition. We aimed to investigate the safety and activity of trifluridine/tipiracil and ramucirumab for previously treated advanced gastric cancer. METHODS: We did an open-label, single-arm, two-cohort, phase 2 study at eight centres in Japan. We enrolled patients with unresectable advanced gastric cancer or gastro-oesophageal junction adenocarcinoma. Cohort A included patients previously treated with one line of chemotherapy without ramucirumab and cohort B included patients previously treated with two to four lines of chemotherapy, including ramucirumab. Patients received trifluridine/tipiracil (35 mg/m2) orally twice daily on days 1-5 and days 8-12 of each 28-day treatment cycle, plus intravenous ramucirumab (8 mg/kg) on days 1 and 15. The primary endpoint was the disease control rate, assessed by investigators and defined as the proportion of patients with a confirmed best overall response, according to Response Evaluation Criteria in Solid Tumors version 1.1. This trial is registered on JapicCTI (JapicCTI-194596) and is ongoing but not recruiting. FINDINGS: Between April 8 and Oct 11, 2019, 64 patients were enrolled and included in the safety and activity analyses, 33 in cohort A and 31 in cohort B. In cohort A, the disease control rate was 85% (95% CI 68-95; 28 of 33 patients) and in cohort B it was 77% (59-90; 24 of 31 patients). Common treatment-related adverse events of grade 3 or worse were neutrophil count decreased (27 [82%] in cohort A and 23 [74%] in cohort B), white blood cell count decreased (eight [24%] and seven [23%]), and platelet count decreased (eight [24%] and four [13%]). Serious treatment-related adverse events were recorded in three patients in cohort A (fatigue and neutrophil count decreased; large intestine perforation; and febrile neutropenia, platelet count decreased, and anaemia). No patients in cohort B had a serious treatment-related adverse event, and no treatment-related deaths were reported in either cohort. INTERPRETATION: Trifluridine/tipiracil and ramucirumab showed an acceptable safety profile and clinical activity in patients with previously treated advanced gastric cancer regardless of previous ramucirumab exposure. FUNDING: Taiho Pharmaceutical and Eli Lilly.

Association between movement control during one-leg standing and femoral BMD in patients with hip fractures.

INTRODUCTION: Prior studies have focused only on the temporal component of one-leg standing, no reports have examined the relationship between the qualitative components of one-leg standing and femoral BMD. Thus, this study investigated whether quality (i.e., movement control) of one-leg standing also associated femoral BMD. MATERIALS AND METHODS: A total of 80 patients with unilateral hip fracture were included in a cross-sectional study. Basic and medical information and physical functions including movement control during one-leg standing were assessed at admission and 2 weeks after surgery, respectively. Hierarchical multiple regression analysis was performed to identify predictors of femoral BMDs on the non-fractured side. Dependent variables included femoral neck and total hip BMDs in models 1 and 2, respectively. RESULTS: Hierarchical multiple regression analysis (standardized partial regression coefficients) in model 1 identified age (- 0.18), sex (0.38), body mass index (BMI) (0.41), movement control during one-leg standing on the non-fractured side (0.19), and life-space assessment (0.17) as factors associating femoral neck BMD. Meanwhile, hierarchical multiple regression analysis (standardized partial regression coefficients) in model 2 identified age (- 0.12), sex (0.36), BMI (0.37), and movement control during one-leg standing on the non-fractured side (0.25) as factors associating total hip BMD. The coefficients of determination adjusted for degrees of freedom (R2) were 0.529 and 0.470 for models 1 and 2, respectively. CONCLUSION: Our results suggest that improving movement control during one-leg standing may be important for maintaining and improving femoral BMD on the non-fractured side.

Simultaneous quantification of arctigenin and its glucuronide conjugate in mouse plasma using ultra-high performance liquid chromatography coupled to tandem mass spectrometry.

Arctigenin is a natural lignin and a main active component of Fructus arctii, the dried fruit of Arctium lappa. This compound was reported to have some biological activities such as anti-inflammatory, antioxidant, antiviral, renoprotective, and antitumor effects. Arctigenin is mainly metabolized to arctigenin-4'-O-glucuronide by UDP-glucuronosyltransferase. In this study, a simultaneous quantification method was established and validated for measuring arctigenin and arctigenin-4'-O-glucuronide in mouse plasma using ultra-high performance liquid chromatography with tandem mass spectrometry. The assay fulfilled the requirements of the United States Food and Drug Administration guideline for assay validation, with a lower limit of quantification of 2.00 ng/mL for arctigenin and 50.0 ng/mL for arctigenin-4'-O-glucuronide. The recovery rate and matrix effect ranged from 78.4 to 102.8% and 92.5 to 106.3%, respectively, for arctigenin, and 74.3 to 109.2% and 94.9 to 110.2% for arctigenin-4'-O-glucuronide. The method was applied to the measurement of plasma concentrations of arctigenin and arctigenin-4'-O-glucuronide in the plasma of mice after administration of arctigenin. All measured concentrations were within the calibration ranges. Our novel method may be useful to measure plasma arctigenin and arctigenin-4'-O-glucuronide concentrations, and contribute to evaluate the pharmacokinetics of arctigenin and arctigenin-4'-O-glucuronide in mice.

An independent component analysis reveals brain structural networks related to TNF-α in drug-naïve, first-episode major depressive disorder: a source-based morphometric study.

In a previous mouse study, social defeat stress-induced microglial activation released tumor necrosis factor-α (TNF-α), leading to neuronal changes in the prefrontal cortex (PFC) and behavioral changes (anxiety). We aimed to investigate the relationship between gray-matter (GM) structural networks and serum TNF-α in patients with major depression disorder (MDD) using multivariate source-based morphometry (SBM). Forty-five first-episode and drug-naïve MDD patients and 38 healthy subjects (HSs) were recruited. High-resolution T1-weighted imaging was performed and serum TNF-α levels were measured in all MDD patients and HSs. After acquiring GM structural networks using SBM, we compared the Z-transformed loading coefficients (Z-scores) between MDD patients and HSs, and investigated the relationship between the Z-scores and the serum TNF-α levels in MDD patients. The serum TNF-α levels in MDD patients were significantly higher than those in HSs. We extracted two independent GM structural networks (the prefrontal network and the insula-temporal network) with significant differences between MDD patients and HSs (-0.305 ± 0.85 and 0.253 ± 0.82; P = 0.03 in the prefrontal network, and -0.268 ± 0.86 and 0.467 ± 0.71; P < 0.01 in the insula-temporal network). The serum TNF-α levels were significantly correlated with the Z-scores in the prefrontal network after Bonferroni correction (r = -0.419, p < 0.01); however, the correlation in the insula-temporal network was not significant (r = -0.290, p = 0.11). Elevated serum TNF-α levels in the early stage of MDD were associated with alteration of the prefrontal network.

Long-Term Performance of Right Ventricular Implantable Cardioverter-Defibrillator Leads in Arrhythmogenic Right Ventricular Cardiomyopathy and Hypertrophic Cardiomyopathy.

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) implanted with implantable cardioverter-defibrillators (ICDs) may show a large decrease in R-wave amplitude during long-term follow-up. However, it is unclear whether this decrease is higher in these patients than in those without structural heart disease. This study investigated ICD-lead intracardiac parameters over a long duration in patients with ARVC and HCM and compared these parameters with those of a control group. We included 50 patients (mean age, 55.2 ± 17.2 years; 26% female) with ICD leads in the right ventricular apex, and compared 7 ARVC and 14 HCM patients with 29 control patients without structural heart disease. ICD-lead parameters, including R-wave amplitude, pacing threshold, and impedance during follow-up, were compared. The difference in these parameters between the time of implantation and year 5 were also compared. There were no significant differences in R-wave amplitude at implantation among the 3 groups. The change in R-wave amplitude between the time of implantation and year 5 was significantly greater in the ARVC group (-3.3 ± 5.4 mV, P = 0.012) in comparison to the control group (1.3 ± 2.8 mV); the HCM group showed no significant difference (-0.4 ± 2.3 mV, P = 0.06). Thus, in the ARVC group, R-wave amplitude at year 5 was significantly lower than that in the control group (5.7 ± 4.8 mV versus 12.5 ± 4.5 mV, P = 0.001). In ARVC patients with ICDs, ventricular sensing is likely to deteriorate during long-term follow-up; however, in HCM patients, sensing may not deteriorate.

Early volume reduction of the hippocampus after whole-brain radiation therapy: an automated brain structure segmentation study.

PURPOSE: To assess atrophy differences among brain regions and time-dependent changes after whole-brain radiation therapy (WBRT). MATERIALS AND METHODS: Twenty patients with lung cancer who underwent both WBRT and chemotherapy (WBRT group) and 18 patients with lung cancer who underwent only chemotherapy (control group) were recruited. Three-dimensional T1WI were analyzed to calculate volume reduction ratio after WBRT in various brain structures. The volume reduction ratio of the hippocampus was compared among following 3 periods: 0-3, 4-7, and 8-11 months after WBRT. RESULTS: The volume reduction ratio of the hippocampus was significantly higher in the WBRT group than in the control group (p < 0.05). In WBRT group, the volume reduction ratio of the hippocampus was significantly higher than that of the cortex and white matter (p < 0.05). There were significant differences in the volume reduction ratio between of 0-3 months and that of 4-7 months (p = 0.02) and between 4-7 months and that of 8-11 months (p = 0.01). CONCLUSION: The hippocampus is more vulnerable to the radiation compared with other brain regions and may become atrophic even in the early stage after WBRT.

Relationship between VEGF-related gene polymorphisms and brain morphology in treatment-naïve patients with first-episode major depressive disorder.

Vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder (MDD). Recently, a genome-wide association study has revealed that four VEGF-related single nucleotide polymorphisms (SNPs) (i.e., rs4416670, rs6921438, rs6993770 and rs10738760) were independently associated with circulating VEGF levels. The current study investigated the relationship between brain volume and these four SNPs in first-episode drug-naïve MDD patients. A total of 38 first-episode drug-naïve MDD patients and 39 healthy subjects (HS) were recruited and underwent high-resolution T1-weighted imaging. Blood samples were collected from all the participants for serum VEGF assays and VEGF-related SNPs genotyping. Genotype-diagnosis interactions related to whole-brain cortical thickness and hippocampal subfield volumes were evaluated for the four SNPs. The results revealed a genotype-diagnosis interaction only for rs6921438 (i.e., the MDD patients and HS with the G/G genotype versus the MDD patients and HS with A-carrier genotype) in the subiculum of the left hippocampus (p < 0.05), and not the other SNPs. There was a volume reduction in the left subiculum of G/G genotype patients compared with the other groups. The "hypochondriasis" scores of the HAMD-17 scale were significantly higher in the G/G genotype patients than the A-carrier genotype patients. The association was observed between VEGF-related SNP rs6921438 and subiculum atrophy in first-episode drug-naïve MDD patients.

Relationship between white matter integrity and serum inflammatory cytokine levels in drug-naive patients with major depressive disorder: diffusion tensor imaging study using tract-based spatial statistics.

Recently, accumulated evidence has indicated a role of inflammation in the pathogenesis of major depressive disorder (MDD). Therefore, we evaluated the relationship between white matter integrity and serum cytokine levels during the first depressive episode in drug-naive MDD patients, using a tract-based spatial statistics (TBSS) method. A total of 35 drug-naive MDD patients with a first depressive episode and 35 healthy subjects (HS) underwent diffusion tensor imaging, and an analysis was conducted using TBSS. We measured serum cytokine levels (interleukin [IL]-1ß, IL-6, interferon-γ, and tumor necrosis factor-α). Fractional anisotropy (FA) values of the bilateral inferior fronto-occipital fasciculus (IFOF) and genu of the corpus callosum in MDD patients were decreased significantly to the HS (p < 0.05 with family-wise error [FWE] correction) and were significantly inversely correlated with the IL-1ß levels (p < 0.05, with FWE correction). No regions showed a correlation between FA values and other serum cytokine levels. Our results suggested that the microstructural changes in IFOF and genu of the corpus callosum are associated with the high IL-1ß levels in the early stage of MDD.

Relationship between interleukin (IL)-6 and brain morphology in drug-naïve, first-episode major depressive disorder using surface-based morphometry.

There is a growing body of evidence to support the involvement of proinflammatory cytokines in the pathophysiology of depression; however, no previous studies have examined the relationship between cytokines and the brain morphology of patients with major depressive disorder (MDD). We therefore evaluated the relationship between serum cytokine levels and cortical thinning during the first depressive episode in drug-naïve patients with MDD. We measured the serum cytokine levels (IL-1ß, IL-6, IFN-γ, and TNFα), and whole-brain cortical thickness and hippocampal subfield volumes on brain magnetic resonance imaging (MRI) using surface-based morphometry in 40 patients with MDD and 47 healthy volunteers (controls). Only the serum IL-6 level was significantly higher in patients with MDD than in controls. The prefrontal cortex (PFC) thickness was significantly reduced in patients with MDD, and showed a significant inverse correlation with the serum IL-6 level. Although high serum IL-6 levels were correlated with reduced left subiculum and right CA1, CA3, CA4, GC-DG, subiculum, and whole hippocampus volumes, the presence or absence of MDD had no effect on the volume of any hippocampal subfields. Our results suggest that IL-6 may play a key role in the morphological changes in the PFC during the early stage of MDD.