The use of generic drugs has been increasing. However, studies of the safety of generic cisplatin (CDDP) for the treatment of head and neck cancer (HNC) have not been reported. This study investigated the treatment completion rates and incidence of CDDP-related adverse events in patients with advanced HNC treated with concurrent chemoradiotherapy (CRT) using generic CDDP. This study included 72 patients who received concurrent CRT using generic CDDP. The number of courses of CDDP was 3 in 45 patients, 2 in 19 patients, and 1 in 8 patients. During 154 courses of 80 mg/m2 generic CDDP, grade 3/4 leukopenia in 21 (14%), neutropenia in 18 (12%), and hypochromia in 8 (5%) cases were reported. Grade 2 elevated serum creatinine occurred in 4 cases (3%), but no grade 3/4 elevated serum creatinine was reported. These results suggest that CRT using generic CDDP is well tolerated in patients with HNC.
Objective: Although safety concerns still remain among patients undergoing unanticipated noncardiac surgery after prior percutaneous coronary intervention (PCI), it has not been directly compared with coronary artery bypass grafting (CABG). The objective of this study was to compare clinical outcomes after noncardiac surgery in patients with prior (>6 months) coronary revascularization by PCI or CABG. Methods: From February 2010 to December 2015, 413 patients with a history of coronary revascularization, scheduled for noncardiac surgery were identified. Patients were divided into PCI group and CABG group and postoperative clinical outcome was compared between 2 groups. The primary outcome was composite of all-cause death, myocardial infarction, and stroke in 1-year follow-up. Results: The 413 patients were divided according to prior coronary revascularization types: 236 (57.1%) into PCI and 177 (42.9%) into CABG group. In multivariate analysis within 1-year follow-up, there was no significant difference in clinical outcome which was composite of all-cause death, myocardial infarction, and stroke (hazard ratio [HR]: 1.50; 95% confidence interval [CI]: 0.76-2.93; P = .24). The same result was present in propensity-matched population analysis (HR: 1.43; 95% CI: 0.68-3.0; P = .34). Conclusions: In patients undergoing noncardiac surgery with prior coronary revascularization by PCI or CABG performed on an average of 42 months after PCI and 50 months after CABG, postoperative clinical outcome at 1-year follow-up is comparable.
Intraventricular hemorrhage (IVH) is a devastating morbidity in preterm infants and can result in poor neurodevelopmental outcomes. Intraventricular hemorrhage usually occurs within 72 hours after birth; post–acute-phase IVH (>1 week after birth) is uncommon. Development of the hemostatic system in fetuses and neonates is an age-dependent evolving process, and the neonatal hemostatic system is characterized by low levels of vitamin K–dependent factors, with further reduction caused by prematurity. Importantly, a severe coagulation deficiency can be a major contributing factor of IVH. Active maternal Crohn disease (CD) during pregnancy causes malnutrition via enteral malabsorption; this may include vitamin K deficiency, resulting in fetal vitamin K deficiency. We herein describe a preterm infant who was born to a mother with CD and developed post–acute-phase IVH due to coagulopathy despite vitamin K administration.
Postoperative cognitive dysfunction (POCD) has been one of the most common problems in elderly patients following surgery. But the specific mechanism of POCD is still not clear. To further understand the reason of these postoperative behavioral deficits, we evaluated the spatial learning memory of both adult (3 months) and aged (18 months) male mice, 3 or 28 days after isoflurane (Iso) exposure for two hours or appendectomy (App). Hippocampal microglia activation and IL-1β, TNF-α, and IFN-γ expression were also evaluated at day 3, day 14 and day 28 after Iso exposure or appendectomy. Results showed that spatial learning memory of aged, but not adult, mice was impaired after Iso exposure or appendectomy, accompanied with more hippocampal microglia activation and IL-1β, TNF-α, and IFN-γ overexpression. These findings suggest that the cognitive deficits of elderly patients who have undergone surgeries are quite possibly caused by hippocampal microglia overactivation and the subsequent inflammation.
Spleen tyrosine kinase (SYK) is a cytoplasmic enzyme that promotes survival and proliferation of B cells. SYK inhibition has shown promising results in the treatment of arthritis and chronic lymphocytic leukemia (CLL). However, in other context, it has been shown that SYK overexpression in epithelial cancer cells induced senescence in p53-dependent mechanism, which underscored its antineoplastic activity in vitro. Here, we show that SYK was induced in response of DNA damage in parallel with p53 levels. In addition, using chemical inhibitors of SYK reduced p53 levels in HCT116 and HT1080 cell lines, which underlines the role of SYK inhibition on p53 activity. Furthermore, SYK inhibition modulated the cell growth, which resulted in a decreasing in cell death. Interestingly, SYK expression showed a positive prognosis in patients with solid tumors in correlations with their survival rates, as expected negative correlation was seen between SYK expression and survival rate of patients with CLL. In conclusion, these findings demonstrate that SYK inhibition modulates p53 expression and activity in HCT116 and HT1080 cells. Reconsidering using of SYK inhibitors in clinical setting in the future should be evaluated carefully in accordance with these findings to prevent the formation of secondary malignancies.
Purpose: Oral care in hospitalized patients with psychiatric disorders is important. However, some patients with psychiatric disorders cannot undergo oral care because of psychiatric symptoms and cognitive decline. The effect of a standardized oral hygiene intervention on the prevention of pneumonia in hospitalized patients with psychiatric disorders was investigated. Method: Patients were divided into 2 groups: control group (N = 259), patients without standardized intervention who were enrolled on April 2014 as the time point of baseline, and intervention group (N = 263), patients with standardized intervention who were enrolled on April 2015 as the time point of baseline. Two end points were evaluated: (1) pneumonia onset within 1 year after the enrollment and (2) no pneumonia for 1 year after the enrollment. The following parameters were compared between the groups: sex, age, psychiatric disorders, past history of diseases of the respiratory system, hypertension, diabetes, hyperlipidemia, heart impairment, and pneumonia. Results: No statistically significant differences were found between the 2 groups in the distributions of characteristics except pneumonia by univariate analysis. The presence of pneumonia was significantly associated with age and the absence of the standardized oral hygiene intervention by multivariate logistic regression analysis. Conclusions: The standardized oral hygiene intervention appears to be effective for preventing pneumonia in patients with psychiatric disorders.
Neisseria gonorrhoeae , the human obligate pathogen responsible for the sexually transmitted disease gonorrhea, has evolved several mechanisms to evade the host immune response. One such mechanism is the modulation of host cell death pathways. In this study, we defined cell death pathways induced by N gonorrhoeae in human monocyte-derived macrophages (MDMs). In a dose-dependent manner, N gonorrhoeae stimulation of MDMs resulted in caspase 1 and 4–dependent cell deaths, indicative of canonical and noncanonical pyroptosis, respectively. Internalization of bacteria or stimulation with lipooligosaccharide (LOS) specifically induced pyroptosis in MDMs and increased secretion of IL-1β. Collectively, our results demonstrate that N gonorrhoeae induces inflammatory pyroptosis in human macrophages due in part to intracellular LOS. We propose that this in turn may exacerbate inflammatory outcomes observed during mucosal infection.
We report an elderly male patient with hyperammonemia induced by intrahepatic portal-systemic shunt without cirrhosis (IPSSwoC). The occasional emergence of his erratic behaviors was misdiagnosed as a psychiatric disorder. Regardless of his uneven symptoms, IPSSwoC was suspected due to his hyperammonemia. The contrast computed tomography of the abdomen revealed a congenital type of IPSSwoC. As blood ammonia levels are inconstant, repeated blood tests are recommended when this disease is suspected in elderly patients with psychiatric symptoms.
The patient was a 66-year-old woman, G2P2. The patient presented a chief complaint of irregular postmenopausal bleeding 1 month ago. A transvaginal ultrasonography showed that bilateral ovaries were not enlarged and uterine endometrium was thickened, measuring at 9 mm. As a result of endometrial curettage, the simple endometrial hyperplasia was revealed. A blood examination showed an elevated estradiol level of 67 pg/mL, an elevated level of testosterone 0.64 ng/mL, and a slightly suppressed follicle-stimulating hormone (FSH) level of 34.86 mIU/mL. We conducted laparoscopic hysterectomy and bilateral salpingo-oophorectomy because the patient strongly suggested less invasive surgery. The result of pathological diagnosis was Sertoli-Leydig cell tumor (SLCT) in moderately differentiation. A blood examination after a month postoperatively revealed an elevated FSH level of 85.59 mIU/mL, depressed estradiol level of less than 10 pg/mL, and testosterone level of less than 0.03 ng/mL. There was no evidence of recurrence in the first year of follow-up.
KillerRed (KR) is a recently discovered fluorescent protein that, when activated with green light, releases reactive oxygen species (ROS) into the cytoplasm, triggering apoptosis in a KR-expressing cell. This property allows for the use of KR as a means of killing cells in an organism with great temporal and spatial specificity, while minimizing the nonspecific effects that can result from mechanical or chemical exposure damage techniques. Such optogenetic control of cell death, and the resulting ability to induce the targeted death of specific tissues, is invaluable for regeneration/repair studies–-particularly in Xenopus laevis, where apoptosis plays a key role in regeneration and repair. We here describe a method by which membrane-bound KR, introduced to Xenopus embryos by mRNA microinjection, can be activated with green light to induce apoptosis in specific organs and tissues, with a focus on the developing eye and pronephric kidney.
Background Because of the potential anti-inflammatory effects, linagliptin, a therapeutic dipeptidyl peptidase-4 inhibitor, is used as an effective drug for diabetic patients for whom inflammation is a prognosis-related factor. We investigated the anti-inflammatory mechanism of linagliptin using seven markers. Methods We pretreated human umbilical vein endothelial cells (HUVECs), with linagliptin and lipopolysaccharide (LPS). The cytosolic fractions were evaluated for protein kinase A (PKA), protein kinase B (PKB), protein kinase C (PKC), ratio of reactive oxygen species (ROS) and Cu/Zn superoxide dismutase (SOD), activator protein 1 (AP-1), and adenosine 3′,5′-cyclic monophosphate (cAMP). Results Linagliptin increased the PKA and PKC activities and the cAMP levels in LPS-treated cells. However, it inhibited LPS-induced PKB phosphorylation, ratio of ROS and Cu/Zn SOD, and LPS-stimulated AP-1 nuclear translocation. Conclusion We reaffirmed the anti-inflammatory and antioxidant effects of linagliptin. These effects might be related to the three protein kinases. Our findings suggest that linagliptin has a wide range of anti-inflammatory effects.
A case of late-infantile Krabbe disease in a patient who presented with developmental regression and spastic quadriplegia in late infancy is reported. Brain magnetic resonance imaging (MRI) at 11 months of age showed predominant corticospinal tract involvement, which usually appears in adult Krabbe disease. Galactocerebrosidase activity in lymphocytes and skin fibroblasts was very low. Genetic testing revealed compound heterozygous mutations of the galactocerebrosidase (GALC) gene, c.635_646 delinsCTC and c.1901T>C [p.L618S], both of which are known pathogenic mutations. It has been reported that the c.1901T>C [p.L618S] mutation is associated with the late-onset phenotype and, in a past case, a homozygous mutation at this location showed predominant corticospinal tract involvement on MRI. Although further analysis is needed to identify the pathophysiological mechanism, this combination of mutations is likely to be associated with this unusual MRI finding in late-infantile Krabbe disease. Because these types of mutations are common for Japanese patients, it is possible that there are more undiagnosed and late-diagnosed patients of late-infantile Krabbe disease who display limited lesions on MRI. Pediatricians should be aware that patients with late-infantile Krabbe disease can present with predominant corticospinal tract involvement on MRI.
Background: Chorioamnionitis (CAM) is an important risk factor for the development of bronchopulmonary dysplasia (BPD) in preterm infants. Objectives: To evaluate the effects of CAM on the development of BPD using interleukin 6 (IL-6), Krebs von den Lungen 6 (KL-6), and transforming growth factor β1 (TGF-β1) in the amniotic fluid as markers for inflammation, lung injury, and fibrosis/remodeling, respectively. Methods: Amniotic fluid concentrations of IL-6, KL-6, and TGF-β1 were measured with enzyme-linked immunosorbent assay or electrochemiluminescence immunoassay. Results: Of the 36 preterm infants, 18 were exposed to histologically confirmed CAM. Of these, 12 were later diagnosed as having BPD. The IL-6, KL-6, and TGF-β1 levels in the amniotic fluid significantly increased with increasing histologic severity of CAM. Moreover, these markers were higher in the BPD group with histologic CAM than those without. Conclusions: Our study suggests that CAM is likely to induce inflammatory, injury, and remodeling processes in the fetal lung.
Purpose Depression is frequently observed in people with diabetes. The purpose of this study is to develop a tool for individuals with diabetes and depression to communicate their comorbid conditions to health-care providers. Method We searched the Internet to review patient-held medical records (PHRs) of patients with diabetes and examine current levels of integration of diabetes and depression care in Japan. Results Eight sets of PHRs were found for people with diabetes. All PHRs included clinical follow-up of diabetes and multidisciplinary clinical pathways for diabetes care. No PHRs included depression monitoring and/or treatment. In terms of an integrated PHR for a patient comorbid with diabetes and depression, necessary components include hopes/preferences, educational information on diabetes complications and treatment, medical history, stress and coping, resources, and monitoring diabetes and depression. Conclusion A new PHR may be suitable for comorbid patients with diabetes and depression.
Chorioamnionitis (CAM) is an important risk factor for the development of bronchopulmonary dysplasia (BPD) in preterm infants. To evaluate the effects of CAM on the development of BPD using interleukin 6 (IL-6), Krebs von den Lungen 6 (KL-6), and transforming growth factor β (TGF-β ) in the amniotic fluid as markers for inflammation, lung injury, and fibrosis/remodeling, respectively. Amniotic fluid concentrations of IL-6, KL-6, and TGF-β were measured with enzyme-linked immunosorbent assay or electro-chemiluminescence immunoassay. Of the 36 preterm infants, 18 were exposed to histologically confirmed CAM. Of these, 12 were later diagnosed as having BPD. The IL-6, KL-6, and TGF-β levels in the amniotic fluid significantly increased with increasing histologic severity of CAM. Moreover, these markers were higher in the BPD group with histologic CAM than those without. Our study suggests that CAM is likely to induce inflammatory, injury, and remodeling processes in the fetal lung.
Background The aim of this study was to identify the unique molecular characteristics of biliary tract cancer (BTC) for the development of novel molecular-targeted therapies. Materials and Methods We performed mutational analysis of KRAS, BRAF, PIK3CA, and FBXW7 and immunohistochemical analysis of EGFR and TP53 in 63 Japanese patients with BTC and retrospectively evaluated the association between the molecular characteristics and clinicopathological features of BTC. Results KRAS mutations were identified in 9 (14%) of the 63 BTC patients; no mutations were detected within the analyzed regions of BRAF, PIK3CA, and FBXW7. EGFR overexpression was observed in 5 (8%) of the 63 tumors, while TP53 overexpression was observed in 48% (30/63) of the patients. Overall survival of patients with KRAS mutation was significantly shorter than that of patients with the wild-type KRAS gene (P = 0.005). By multivariate analysis incorporating molecular and clinicopathological features, KRAS mutations and lymph node metastasis were identified to be independently associated with shorter overall survival (KRAS, P = 0.004; lymph node metastasis, P = 0.015). Conclusions Our data suggest that KRAS mutation is a poor prognosis predictive biomarker for the survival in BTC patients.
Familial dysalbuminemic hyperthyroxinemia (FDH) is a familial autosomal dominant disease caused by mutation in the albumin gene that produces a condition of euthyroid hyperthyroxinemia. In patients with FDH, serum-free thyroxine (FT4) and free triiodothyronine (FT3) concentrations as measured by several commercial methods are often falsely increased with normal thyrotropin (TSH). Therefore, several diagnostic steps are needed to differentiate TSH-secreting tumor or generalized resistance to thyroid hormone from FDH. We herein report a case of a Japanese man born in Aomori prefecture, with FDH caused by a mutant albumin gene (R218P). We found that a large number of FDH patients reported in Japan to date might have been born in Aomori prefecture and have shown the R218P mutation. In conclusion, FDH needs to be considered among the differential diagnoses in Japanese patients born in Aomori prefecture and showing normal TSH levels and elevated FT4 levels.