Search Results (29)

Background: Bone metastasis is associated with a poor prognosis. Bone-modifying agents (BMA) are commonly used for the prevention or treatment of skeletal-related events (SRE) in patients with bone metastasis; however, whether or not treatment with BMA improves survival remains unclear. In this study, we investigated whether BMA was involved in post-bone metastasis survival. Methods: A total of 539 cancer patients were retrospectively analyzed to identify significant independent factors in post-bone metastasis survival. Results: Among the overall population, patients with the following cancers had a median survival longer than 24 months: thyroid, 97.2 months; breast, 51.5 months; prostate, 47.2 months; and kidney, 38.8 months. In contrast, median post-bone metastasis survival was significantly shorter in gastrointestinal (GI) (6.5 months), head and neck (6.3 months), and urinary tract (3.4 months) cancers. In non-small cell lung cancer (NSCLC), the log-rank test demonstrated that the epidermal growth factor receptor (EGFR) mutation was a significant factor for post-bone metastasis survival: EGFR mutation (−) n = 67, median post-bone metastasis survival 11.5 months (95% CI: 6.0–15.2); EGFR mutation (+) n = 39, median post-bone metastasis survival 28.8 months (95% CI: 18.1–35.7) (p < 0.05). Intriguingly, treatment with BMA was a significant positive prognostic factor: BMA (−) n = 203, median post-bone metastasis survival 7.8 months (95% CI: 5.8–12.5); BMA (+) n = 336, median post-bone metastasis survival 21.9 months (95% CI: 16.1–26.4) (p < 0.001). Moreover, the Cox proportional hazards model showed that this was particularly evident in cancer types with poor prognosis such as GI cancer (hazard ratio [HR]: 0.62, 95% CI: 0.40–0.95; p < 0.05) and NSCLC without the epidermal growth factor receptor (EGFR) mutation (HR: 0.56, 95% CI: 0.34–0.91; p < 0.05). Conclusions: Treatment with BMA is recommended not only for the prevention and/or treatment of SRE, but also may have a positive impact on post-bone metastasis survival, particularly in cancers with typically poor post-bone metastasis survival such as GI cancer and NSCLC without the EGFR mutation. Full article

Background: Investigating the association between plasma-free amino acids (PFAAs) and hyperuricemia (HU) in dyslipidemia (DL) and dyslipidemia with hypertension (DH) is crucial, as it could provide valuable insights into the pathophysiology of these conditions and contribute to the development of targeted prevention and management strategies. Therefore, in this study, we aimed to elucidate the associations between PFAAs and HU in individuals with DL and DH. Methods: We quantified PFAAs and uric acid levels among Japanese healthy subjects (n = 1311; HU, n = 57), subjects with DL (n = 1483; HU, n = 219), and subjects with DH (n = 1159; HU, n = 237). Results: The concentrations of most PFAAs showed significant differences between subjects without and with HU across all groups (p < 0.05 to 0.001). Adjusted logistic regression analyses revealed that certain PFAAs were consistently positively or negatively associated with HU across all groups. Specifically, in the DL group, alanine, tryptophan, and tyrosine showed significant positive associations with HU, while in the DH group, citrulline and glutamate exhibited similar positive associations (p < 0.05 to 0.001). Conversely, threonine in the healthy group (p < 0.05) and glutamine in the DL group (p < 0.05) demonstrated significant inverse associations with HU. Conclusions: This study revealed a potential close relationship between alterations in PFAA profiles and HU in dyslipidemia, without and with hypertension. The findings warrant further research to elucidate the role of altered amino acid and uric acid levels as potential disease biomarkers and therapeutic targets. Full article

Background: The utility of using indirect calorimetry (IC) to estimate energy needs and methods for its application to this purpose remain unclear. This systematic review investigated whether using IC to estimate energy expenditure in critically ill patients is more meaningful for improving survival than other estimation methods. Methods: Comprehensive searches were conducted in MEDLINE using PubMed, Cochrane Central Register of Controlled Trials, and Igaku-Chuo-Zasshi up to March 2023. Results: Nine RCTs involving 1178 patients were included in the meta-analysis. The evidence obtained suggested that energy delivery by IC improved short-term mortality (risk ratio, 0.86; 95% confidence interval [CI], 0.70 to 1.06). However, the use of IC did not appear to affect the length of ICU stay (mean difference [MD], 0.86; 95% CI, −0.98 to 2.70) or the duration of mechanical ventilation (MD, 0.66; 95% CI, −0.39 to 1.72). Post hoc analyses using short-term mortality as the outcome found no significant difference by target calories in resting energy expenditure, whereas more frequent IC estimates were associated with lower short-term mortality and were more effective in mechanically ventilated patients. Conclusions: This updated meta-analysis revealed that the use of IC may improve short-term mortality in patients with critical illness and did not increase adverse events. Full article

Congenital malformations are functional and structural alterations in embryonic or foetal development resulting from a variety of factors including maternal health status. This study aimed to investigate the association between maternal birth weight (MBW) and the prevalence of congenital malformations in offspring using data from a nationwide birth cohort study in Japan including 103,060 pregnancies. A binary logistic regression model with adjustment for various covariates revealed that an MBW of <2500 g (low MBW) was associated with an increased risk of congenital heart disease (adjusted odds ratio: 1.388, [95% confidence interval: 1.075–1.792]), angioma (1.491 [1.079–2.059]), and inguinal hernia (1.746, [1.189–2.565]), while those with an MBW of ≥4000 g (high MBW) were associated with congenital anomalies of the urinary tract (2.194, [1.261–3.819]) and arrhythmia (1.775, [1.157–2.725]) compared with those with an MBW of 3000–3499 g. Low MBW was associated with cleft lip and/or palate (1.473, [1.052–2.064]), congenital heart disease (1.615, [1.119–2.332]), genital organs (1.648, [1.130–2.405]), hypospadias (1.804, [1.130–2.881]), and inguinal hernia (1.484, [1.189–1.851]) in male infants and CAKUT (1.619, [1.154–2.273]) in female infants, whereas high MBW was associated with congenital heart disease (1.745, [1.058–2.877]) and CAKUT (2.470, [1.350–4.517]) in male infants. The present study is the first to demonstrate a link between MBW and congenital malformations in Japanese children. While these results must be interpreted with caution, MBW should be considered a major predictor of congenital malformation risk. Full article

The role of neuroinflammation in the pathophysiology of migraines is increasingly being recognized, and cytokines, which are important endogenous substances involved in immune and inflammatory responses, have also received attention. This review examines the current literature on neuroinflammation in the pathogenesis of migraine. Elevated TNF-α, IL-1β, and IL-6 levels have been identified in non-invasive mouse models with cortical spreading depolarization (CSD). Various mouse models to induce migraine attack-like symptoms also demonstrated elevated inflammatory cytokines and findings suggesting differences between episodic and chronic migraines and between males and females. While studies on human blood during migraine attacks have reported no change in TNF-α levels and often inconsistent results for IL-1β and IL-6 levels, serial analysis of cytokines in jugular venous blood during migraine attacks revealed consistently increased IL-1β, IL-6, and TNF-α. In a study on the interictal period, researchers reported higher levels of TNF-α and IL-6 compared to controls and no change regarding IL-1β levels. Saliva-based tests suggest that IL-1β might be useful in discriminating against migraine. Patients with migraine may benefit from a cytokine perspective on the pathogenesis of migraine, as there have been several encouraging reports suggesting new therapeutic avenues. Full article

Background: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recommended for patients with chronic liver diseases as the vaccine can prevent and/or reduce the severity of SARS-CoV-2 infection. However, we have little information on the often-reported liver-related adverse events (LrAEs) caused by the mRNA vaccine. Methods: We retrospectively investigated the frequency and details of severe LrAEs and changes in liver function tests in patients with chronic liver diseases. Results: Among 431 patients with chronic liver diseases, 416 (96.5%) had received the SARS-CoV-2 vaccine ≥ 2 times. Among the 345 patients included in the analysis, 6 (1.7%) had severe LrAEs; 3 ascites, 2 increases in transaminases, and 1 an increase in total bilirubin. Multivariate analysis demonstrated that cirrhosis and autoimmune disease were risk factors for severe LrAEs. In contrast, the liver function reserve assessed by the Child–Pugh and ALBI scores did not markedly change after vaccination in patients with cirrhosis and/or autoimmune diseases despite a small increase in transaminase levels. Conclusion: SARS-CoV-2 mRNA vaccines, which were used in most of our patients, are safe in patients with chronic liver diseases, but the frequency of severe LrAEs is slightly increased in patients with cirrhosis and/or autoimmune diseases. Full article

Western-type diet with high salt and sugar, sedentary behavior, obesity, tobacco and alcoholism are important risk factors for hypertension. This review aims to highlight the role of western diet-induced oxidative stress and inflammation in the pathogenesis of hypertension and the role of various types of diets in its prevention with reference to dietary approaches to stop hypertension (DASH) diet. It seems that it is crucial to alter the western type of diet because such diets can also predispose all CVDs. Western diet-induced oxidative stress is characterized by excessive production of reactive oxygen species (ROS) with an altered oxidation-reduction (redox) state, leading to a marked increase in inflammation and vascular dysfunction. Apart from genetic and environmental factors, one important cause for differences in the prevalence of hypertension in various countries may be diet quality, deficiency in functional foods, and salt consumption. The role of the DASH diet has been established. However, there are gaps in knowledge about the role of some Indo-Mediterranean foods and Japanese foods, which have been found to decrease blood pressure (BP) by improving vascular function. The notable Indo-Mediterranean foods are pulses, porridge, spices, and millets; fruits such as guava and blackberry and vegetables, which may also decrease BPs. The Japanese diet consists of soya tofu, whole rice, in particular medical rice, vegetables and plenty of fish rich in fish oil, fish peptides and taurine that are known to decrease BPs. Epidemiological studies and randomized, controlled trials have demonstrated the role of these diets in the prevention of hypertension and metabolic diseases. Such evidence is still meager from Japan, although the prevalence of hypertension is lower (15–21%) compared to other developed countries, which may be due to the high quality of the Japanese diet. Interestingly, some foods, such as berries, guava, pumpkin seeds, carrots, soya beans, and spices, have been found to cause a decrease in BPs. Omega-3 fatty acids, fish peptide, taurine, dietary vitamin D, vitamin C, potassium, magnesium, flavonoids, nitrate and l-arginine are potential nutrients that can also decrease BPs. Larger cohort studies and controlled trials are necessary to confirm our views. Full article

Nna1/CCP1 is generally known as a causative gene for a spontaneous autosomal recessive mouse mutation, Purkinje cell degeneration (pcd). There is enough evidence that the cytosolic function of the zinc carboxypeptidase (CP) domain at the C-terminus of the Nna1 protein is associated with cell death. On the other hand, this molecule’s two nuclear localization signals (NLSs) suggest some other functions exist. We generated exon 3-deficient mice (Nna1^N KO), which encode a portion of the N-terminal NLS. Despite the frameshift occurring in these mice, there was an expression of the Nna1 protein lacking the N-terminal side. Surprisingly, the pcd phenotype did not occur in the Nna1^N KO mouse. Behavioral analysis revealed that they were less anxious when assessed by the elevated plus maze and the light/dark box tests compared to the control. Furthermore, they showed impairments in context-dependent and sound stimulus-dependent learning. Biochemical analysis of Nna1^N KO mice revealed a reduced level of the AMPA-type glutamine receptor GluA2 in the hippocampal synaptosomal fraction. In addition, the motor protein kinesin-1, which transports GluA2 to dendrites, was also decreased. These results indicate that Nna1 is also involved in emotion and memory learning, presumably through the trafficking and expression of synaptic signaling molecules, besides a known role in cell survival. Full article

Background and Objectives: Brain atrophy is related to cognitive decline. However, the heritability of brain atrophy has not been fully investigated in the Eastern Asian population. Materials and Methods: Brain imaging of 74 Japanese twins registered in the Osaka University Twin Registry was conducted with voxel-based morphometry SPM12 and was processed by individual voxel-based morphometry adjusting covariates (iVAC) toolbox. The atrophy of the measured lobes was obtained by comparing the focal volume to the average of healthy subjects. Classical twin analysis was used to measure the heritability of its z-scores. Results: The heritability of brain atrophy ranged from 0.23 to 0.97, depending upon the lobes. When adjusted to age, high heritability was reported in the frontal, frontal-temporal, and parietal lobes, but the heritability in other lobes was lower than 0.70. Conclusions: This study revealed a relatively lower heritability in brain atrophy compared to other ethnicities. This result suggests a significant environmental impact on the susceptibility of brain atrophy the Japanese. Therefore, environmental factors may have more influence on the Japanese than in other populations. Full article

Background: We dealt with the occurrence of an outbreak of Candida parapsilosis in a neonatal intensive care unit (NICU) in September 2020. There have been several reports of C. parapsilosis outbreaks in NICUs. In this study we describe our investigation into both the transmission route and the biofilm of C. parapsilosis. Methods: C. parapsilosis strains were detected in three inpatients and in two environmental cultures in our NICU. One environmental culture was isolated from the incubator used by a fungemia patient, and another was isolated from the humidifier of an incubator that had been used by a nonfungemia patient. To prove their identities, we tested them by micro satellite analysis. We used two methods, dry weight measurements and observation by electron microscopy, to confirm biofilm. Results: Microsatellite analysis showed the five C. parapsilosis cultures were of the same strain. Dry weight measurements and electron microscopy showed C. parapsilosis formed biofilms that amounted to clumps of fungal cells. Conclusions: We concluded that the outbreak happened due to horizontal transfer through the humidifier of the incubator and that the C. parapsilosis had produced biofilm, which promoted an invasive and infectious outbreak. Additionally, biofilm is closely associated with pathogenicity. Full article

Background: Conventional therapies, including chemoembolization and radiation therapy, have been expected to prolong the prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases, which remains poor. However, little information is available on the efficacy of conventional therapies for such patients under tyrosine kinase inhibitor (TKI) treatment. Methods: We retrospectively investigated 127 HCC patients with extrahepatic metastases, who were divided into the non-TKI (conventional therapies) and TKI groups and further subdivided into the TKI alone and TKI plus conventional therapies groups. Conventional therapies included transcatheter arterial chemoembolization, cisplatin-based chemotherapy, radiation, surgery, and UFT, an oral chemotherapeutic agent. Results: The median of the overall survival (OS) of the 127 patients with extrahepatic metastases was 7.0 months. Meanwhile, the median OS of the TKI and non-TKI groups was 12.1 and 4.1 months, respectively. Imitating TKI after diagnosing metastases promoted a favorable increase in OS. Among the TKI group, the median OS in the TKI alone group was 8.9 months. TKI plus conventional therapies promoted no improvement in OS after adjusting for the patients’ background data. Conclusion: TKI promoted a better OS in HCC patients with extrahepatic metastases compared to conventional therapies. However, TKI plus conventional therapies promoted no improvement in the prognosis of such patients. Full article

The role of Dickkopf-3 (Dkk3)/REIC (The Reduced Expression in Immortalized Cells), a Wnt-signaling inhibitor, in male reproductive physiology remains unknown thus far. To explore the functional details of Dkk3/REIC in the male reproductive process, we studied the Dkk3/REIC knock-out (KO) mouse model. By examining testicular sections and investigating the sperm characteristics (count, vitality and motility) and ultrastructure, we compared the reproductive features between Dkk3/REIC-KO and wild-type (WT) male mice. To further explore the underlying molecular mechanism, we performed RNA sequencing (RNA-seq) analysis of testicular tissues. Our results showed that spermiation failure existed in seminiferous tubules of Dkk3/REIC-KO mice, and sperm from Dkk3/REIC-KO mice exhibited inferior motility (44.09 ± 8.12% vs. 23.26 ± 10.02%, p < 0.01). The Ultrastructure examination revealed defects in the sperm fibrous sheath of KO mice. Although the average count of Dkk3/REIC-KO epididymal sperm was less than that of the wild-types (9.30 ± 0.69 vs. 8.27 ± 0.87, ×10⁶), neither the gap (p > 0.05) nor the difference in the sperm vitality rate (72.83 ± 1.55% vs. 72.50 ± 0.71%, p > 0.05) were statistically significant. The RNA-seq and GO (Gene Oncology) enrichment results indicated that the differential genes were significantly enriched in the GO terms of cytoskeleton function, cAMP signaling and calcium ion binding. Collectively, our research demonstrates that Dkk3/REIC is involved in the process of spermiation, fibrous sheath integrity maintenance and sperm motility of mice. Full article

Malignant gliomas are associated with extremely poor clinical outcomes in both humans and dogs, and novel therapies are needed. Glioma-bearing canine patients may serve as promising preclinical models for human therapies, including complementary medicine. The objective of this study was to evaluate the effects of mistletoe extract (Viscum album) alone and in combination with mebendazole in an in vitro model of canine high-grade astrocytoma using the cell line SDT-3G. SDT-3G cells were exposed to a range of concentrations of mistletoe extract alone to obtain an IC50. In separate experiments, cells were exposed to mebendazole at a previously determined IC50 (0.03 µM) alone or in conjunction with varying concentrations of mistletoe extract to determine the additive effects. The IC50 for mistletoe alone was 5.644 ± 0.09 SD μg/mL. The addition of mistletoe at 5 μg/mL to mebendazole at 0.03 µM led to increased cell death compared to what would be expected for each drug separately. The cytotoxicity of mistletoe in vitro and its additive effect with mebendazole support future expanded in vitro and in vivo studies in dogs and supply early evidence that this may be a useful adjunct therapeutic agent for use in glioma-bearing dogs. To the authors’ knowledge, this is the first published report of Viscum album extract in canine glioma. Full article

Immune checkpoint inhibitors (ICIs) confer remarkable therapeutic benefits to patients with various cancers. However, many patients are non-responders or develop resistance following an initial response to ICIs. There are no reliable biomarkers to predict the therapeutic effect of ICIs. Therefore, this study investigated the clinical implications of plasma levels of soluble anti-programmed death-1 (sPD-1) in patients with cancer treated with ICIs. In total, 22 patients (13 with non-small-cell lung carcinoma, 8 with gastric cancer, and 1 with bladder cancer) were evaluated for sPD-1 concentration using enzyme-linked immunosorbent assays for diagnostic and anti-PD-1 antibody analyses. sPD-1 levels were low before the administration of anti-PD-1 antibodies. After two and four cycles of anti-PD-1 antibody therapy, sPD-1 levels significantly increased compared with pretreatment levels (p = 0.0348 vs. 0.0232). We observed an increased rate of change in plasma sPD-1 concentrations after two and four cycles of anti-PD-1 antibody therapy that significantly correlated with tumor size progression (p = 0.024). sPD-1 may be involved in resistance to anti-PD-1 antibody therapy, suggesting that changes in sPD-1 levels can identify primary ICI non-responders early in treatment. Detailed analysis of each cancer type revealed the potential of sPD-1 as a predictive biomarker of response to ICI treatment in patients with cancer. Full article

Background: A carbapenem-resistant Enterobacteriaceae (CRE) outbreak occurred in an advanced emergency medical service center [hereafter referred to as the intensive care unit (ICU)] between 2016 and 2017. Aim: Our objective was to evaluate the infection control measures for CRE outbreaks. Methods: CRE strains were detected in 16 inpatients located at multiple sites. Environmental cultures were performed and CRE strains were detected in 3 of 38 sites tested. Pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), and detection of β-lactamase genes were performed against 25 CRE strains. Findings: Molecular typing showed the PFGE patterns of two of four Klebsiella pneumoniae strains were closely related and the same MLST (ST2388), and four of five Enterobacter cloacae strains were closely related and same MLST (ST252). Twenty-three of 25 CRE strains harbored the IMP-1 β-lactamase gene and 15 of 23 CRE strains possessed IncFIIA replicon regions. Despite interventions by the infection control team, new inpatients with the CRE strain continued to appear. Therefore, the ICU was partially closed and the inpatients with CRE were isolated, and the ICU staff was divided into two groups between inpatients with CRE and non-CRE strains to avoid cross-contamination. Although the occurrence of new cases dissipated quickly after the partial closure, a few months were required to eradicate the CRE outbreak. Conclusion: Our data suggest that the various and combined measures that were used for infection control were essential in stopping this CRE outbreak. In particular, partial closure to isolate the ICU and division of the ICU staff were effective. Full article