Five‐year efficacy of finasteride in 801 Japanese men with androgenetic alopecia

Finasteride is standard medical treatment for androgenetic alopecia; however, no large studies with 5 years or more of follow up have been performed in Japan. The authors followed Japanese men with androgenetic alopecia treated with finasteride for 5 years to evaluate long‐term treatment efficacy. Of 903 men treated with finasteride (1 mg/day), 801 patients were evaluated over 5 years by modified global photographic assessment. Although the proportion of improvement was high (99.4%), modified global photographic assessment scores after 5 years of treatment were lower in patients with more advanced disease as measured by the modified Norwood–Hamilton scale. After separating patients into “sufficient” and “insufficient” efficacy groups according to the modified global photographic assessment score after 5 years (scores ≥6 and <6, respectively), multivariate analysis showed that independent risk factors of insufficient efficacy were age at start of treatment of 40 years or more (P = 0.021) and classification on the modified Norwood–Hamilton scale (P < 0.001), whereas presence of stress at start of treatment was a negative predictor (P = 0.025). In conclusion, continuous finasteride treatment for 5 years improved androgenetic alopecia with sustained effect among Japanese. Younger age and less advanced disease at start of treatment were the key predictors of higher finasteride efficacy.     

Does Oil Rich in Alpha-Linolenic Fatty Acid Cause the Same Immune Modulation as Fish Oil in Walker 256 Tumor-Bearing Rats?

Objective: Polyunsaturated fatty acids n-3 (PUFA n-3) have shown effects in reducing tumor growth, in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) abundantly present in fish oil (FO). When these fatty acids are provided in the diet, they alter the functions of the cells, particularly in tumor and immune cells. However, the effects of α-linolenic fatty acid (ALA), which is the precursor of EPA and DHA, are controversial. Thus, our objective was to test the effect of this parental fatty acid. Methods: Non-tumor-bearing and tumor-bearing Wistar rats (70 days) were supplemented with 1 g/kg body weight of FO or Oro Inca® (OI) oil (rich in ALA). Immune cells function, proliferation, cytokine production, and subpopulation profile were evaluated. Results: We have shown that innate immune cells enhanced phagocytosis capacity, and increased processing and elimination of antigens. Moreover, there was a decrease in production of pro-inflammatory cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6)) by macrophages. Lymphocytes showed decreased proliferation capacity, increased cluster of differentiation 8 (CD8⁺) subpopulation, and increased TNF-α production. Conclusions: Oil rich in ALA caused similar immune modulation in cancer when compared with FO.     

Outcomes After Aortic Valve Replacement for Asymptomatic Severe Aortic Regurgitation and Normal Ejection Fraction

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Infective Endocarditis Due to Treponema pallidum: A Case Diagnosed Using Polymerase Chain Reaction Analysis of Aortic Valve

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis.     

Population Pharmacokinetic and Exposure-Response Analyses of Baloxavir Marboxil in Adults and Adolescents Including Patients With Influenza

Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships. Population pharmacokinetic analysis of the baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer. A 2-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing the clearance and distribution volume. A dose regimen based on the body weight (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race; however, the exposures were dependent on the body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups. In conclusion, the population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid.     

Idiopathic myointimal hyperplasia of mesenteric veins: Rare case of ischemic colitis mimicking inflammatory bowel disease

Idiopathic myointimal hyperplasia of mesenteric veins (IMHMV) is a rare and poorly understood ischemic colitis that occurs in the rectosigmoid colon of predominantly young, previously healthy, male patients. A 76‐year‐old Japanese man presented to our hospital with a 1‐year history of worsening diarrhea, lower abdominal pain, and weight loss (−6 kg). Laboratory evaluation revealed white blood cell count of 13 200/μL, C‐reactive protein level of 2.0 mg/dL (normal range, 0.0–0.3), and negative results for stool culture (including Clostridium difficile). Colonoscopy showed circumferential and edematous narrowing of the sigmoid colon with deep longitude ulceration. Biopsy was done and examination of the specimen demonstrated no specific ischemia. The patient was treated with bowel rest, antibiotics, and i.v. fluids; however, his symptoms worsened. Finally, sigmoidectomy was carried out. Histological examination demonstrated significant myointimal hyperplasia of mesenteric veins leading to thickening and stenosis of the venous lumen. Therefore, the final diagnosis was IMHMV. Three months following sigmoidectomy, he was asymptomatic.     

Japanese Versus Non-Japanese Patients with Transient Ischemic Attack or Minor Stroke: Subanalysis of TIA registry.org

BackgroundTIAregistry.org is an international cohort of patients with transient ischemic attack (TIA) or minor stroke within 7 days before enrollment in the registry. Main analyses of 1-year follow-up data have been reported.⁵ We conducted subanalysis on the baseline and 1-year follow-up data of Japanese patients.MethodsThe patients were classified into 2 groups based on Japanese ethnicity, Japanese (345) and non-Japanese (3238), and their baseline data and 1-year event rates were compared. We also determined risk factors and predictors of 1-year stroke.ResultsCurrent smoking, regular alcohol drinking, intracranial arterial stenosis, and small vessel occlusion; and hypertension, dyslipidemia, coronary artery disease, and extracranial arterial stenosis were more and less common among Japanese patients, respectively. Stroke risk was higher and TIA risk was lower at 1-year follow-up among Japanese patients. The baseline risk factors for recurrent stroke were diabetes, alcohol drinking, and large artery atherosclerosis. Independent predictors of 1-year stroke risk were prior congestive heart failure and alcohol consumption.ConclusionsThe two populations of patients featured differences in risk factors, stroke subtypes, and outcome events. Predictors of recurrent stroke among Japanese patients included congestive heart failure and regular alcohol drinking. Strategies to attenuate residual risk of stroke aside from adherence to current guidelines should take our Japanese-patient specific findings into account.     

Influence of SNPs in cytokine-related genes on the severity of food allergy and atopic eczema in children

Although many single nucleotide polymorphism (SNP) studies have reported an association of atopy, allergic diseases and total serum immunoglobulin E (IgE) levels, almost all of these studies sought risk factors for the onset of these allergic diseases. Furthermore, many studies have analyzed a single gene and hardly any have analyzed environmental factors. In these analyses, the results could be masked and the effects of other genes and environmental factors may be decreased. Here, we described the correlation between four genes [interleukin (IL)-4 (C-590T), IL-4 receptor (A1652G), FCER1B (G6842A) and STAT6 (G2964A)] in connection with IgE production; the role of IL-10 (C-627A) as a regulatory cytokine of allergy; and the severity of food allergy (FA) and atopic eczema (AE) in 220 Japanese allergic children. In addition to these SNPs, environmental factors, i.e., patient's attitude, indoor environment, and so on, were also investigated in this study. Our study was retrospective, and the correlation was analyzed by our defined clinical scores divided into three terms: worst symptoms, recent symptoms and general amelioration at the most recent examination during the disease course. Our results indicated that IL-10 AA, the genotype with lower IL-10 production, is associated with higher IgE levels in the serum (p < 0.0001, estimate; 0.912). Marginal liver abnormalities were observed in the subject group with both FA and AE (p < 0.1191, estimate; 0.1490). Our defined clinical scores enabled evaluation of various aspects of disease severity. Based on the scores, while no single SNP selected in this study determined severity, the combination of the SNP with laboratory data and environmental factors appeared to determine severity.