Effects of Combination Therapy with Intravitreal Ranibizumab and Tissue Plasminogen Activator for Neovascular Age-Related Macular Degeneration.

Background: Subretinal hyper-reflective material (SHRM) sometimes causes vision loss in spite of anti-vascular endothelial growth factor (VEGF) therapy in eyes with neovascular age-related macular degeneration (nvAMD). We evaluated the impacts of combination therapy with intravitreal ranibizumab (IVR) and tissue plasminogen activator (tPA) in eyes with nvAMD accompanying SHRM. Methods: In total, 25 eyes of 25 patients (16 men and 9 women, 76.7 years old), who underwent IVR/tPA for nvAMD with SHRM and were followed up for at least 12 months, were retrospectively reviewed. In total, 15 eyes were treatment-naïve and 10 eyes had previous treatment for nvAMD. Results: In total, 16 eyes had type 2 macular neovascularization (MNV), 5 eyes type 1 MNV with fibrovascular pigment epithelial detachment and 4 eyes polypoidal choroidal vasculopathy. At month 12, SHRM regressed or reduced in 18 eyes (72%) and the best-corrected visual acuity (BCVA) improved in 6 eyes (24%) and was unchanged in 14 eyes (56%), while the mean BCVA was just stabilized. The mean central retinal thickness, macular volume and SHRM thickness significantly improved from 408 µm to 287 µm, from 11.9 mm3 to 9.6 mm3, from 369 µm to 165 µm, respectively (p < 0.01). Conclusions: The combination therapy with IVR/tPA for nvAMD with SHRM may help preserve vision by prompt regression of SHRM.

Predictive and prognostic value of stromal tumour-infiltrating lymphocytes before and after neoadjuvant therapy in triple negative and HER2-positive breast cancer.

AIM: Lymphocyte predominant breast cancer (BC) is associated with higher pathological complete response (pCR) rate after neoadjuvant therapy (NAT) and favorable outcome in triple negative breast cancer (TNBC) and HER2+ BC. The predictive and prognostic impact of stromal tumour-infiltrating lymphocytes (TILs) after NAT and the change of TILs before (pre-) and after (post-) NAT are not well studied. We aimed to assess the predictive and prognostic value of pre- and post-NAT TILs, as well as their pharmacodynamics modulation and their change for TNBC and HER2+ BC. MATERIALS AND METHODS: Two-hundred and nine consecutive patients (n = 80 TNBC, n = 129 HER2+ BC) who received NAT between 2001 and 2009 in a single institution were included. We evaluated the association between pre-NAT TILs and pCR, and the association between pre- and post-NAT TILs, as well as their immunodynamics change with relapse-free survival (RFS) for patients with residual disease (RD). RESULTS: Low pre-NAT TILs compared to int/high were significantly associated with lower pCR rate (TNBC: 4.0% vs 43.6%; HER2+ BC: 26.0% vs 51.9%). The median follow-up period was 98 months. In TNBC with RD, low pre-NAT TILs showed significant association with shorter RFS (HR = 3.844 [1.190-12.421], p = 0.024) in multivariate analysis. Low post-NAT TILs showed borderline significant association with shorter RFS (HR = 2.836 [0.951-8.457], p = 0.061). The change in TILs was not associated with RFS. In HER2+ BC, low pre-NAT TILs were not associated with RFS. CONCLUSION: In TN and HER2+ BCs, low pre-NAT TILs tumours had a low likelihood of achieving pCR. In TNBC with RD, both low pre- and post-NAT TILs were associated with shorter RFS. These results suggest that TILs information should be taken into account when additional therapies may be given in the post-neoadjuvant setting.

Association of serum hs-CRP and lipids with obesity in school children in a 12-month follow-up study in Japan.

OBJECTIVES: To investigate the association of serum lipids and high-sensitivity C-reactive protein (hs-CRP) with obesity in school children and to explore whether hs-CRP levels could be used to predict the presence or absence of obesity 12 months later. METHODS: The subjects were school children (6-11 years old) in Japan. Blood sampling and physical measurements were performed in school (2001); low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and hs-CRP levels were measured. Data from children who could be followed 12 months later were analyzed. Subjects weighing 20% or more over his/her standard weight were regarded as obese, and the association of obesity with serum parameters was analyzed. RESULTS: Data from 612 subjects were analyzed (follow-up rate, 75.4%). The mean of each serum parameter was significantly higher (inverse for HDL-C; lower) in obese than that in non-obese children. Logistic regression analysis for obesity at baseline showed that the odds ratio (OR) of hs-CRP was the highest [OR, 2.15; 95% confidence interval (CI), 1.65-2.78 for an interquartile rage (IQR) increase]; the association with triglycerides and LDL-C/HDL-C was significant. At the 12-month follow-up, the OR of high hs-CRP remained the highest of all serum parameters (2.09; 95% CI, 1.63-2.69 for an IQR increase). CONCLUSIONS: High levels of triglycerides, LDL-C/HDL-C, and hs-CRP increased the risk of obesity in school children. Hs-CRP is considered to be a better predictor of obesity 12 months later than is LDL-C/HDL-C.

Effect of hourly concentration of particulate matter on peak expiratory flow in hospitalized children: a panel study.

BACKGROUND: Little information is available on the possible association between hourly short-term air pollution and peak expiratory flow (PEF) in asthmatic children. METHODS: PEF was measured twice daily, from October through December, 2000, in 17 children aged 8 to 15 years hospitalized with severe asthma. A total of 1198 PEF measurements were made at 7 a.m. and 1175 at 7 p.m. Measurements were conducted immediately prior to medication under the guidance of trained nurses. PEF changes were estimated in 10-µg/m3 increments of particulate matter with a 50% cut-off aerodynamic diameter of ≤2.5 µm (PM2.5), with adjustment for sex, age, height, and temperature. Lagged-hour exposures of up to 24 hours were examined. RESULTS: Increased 24-hour mean concentration of PM2.5 was associated with a decrease in both morning and evening PEF (-3.0 l/minute; 95%CI: -4.6, -1.4 and -4.4 l/minute; 95%CI: -7.1, -1.7, respectively). In addition, hourly concentrations of PM2.5 and PEF showed a significant association between some lags of PM2.5 and PEF. Effect size was almost -3 l/minute in both morning and evening PEF for an hourly PM2.5 concentration of 10 µg/m3 in several lags. Even after adjustment for other air pollutants, some of the significant associations with PEF remained. CONCLUSION: Among hospitalized children with severe asthma, increased hourly concentration of PM2.5 was associated with a decrease in PEF.

Modifying effect of age on the association between ambient ozone and nighttime primary care visits due to asthma attack.

BACKGROUND: We examined the association between short-term exposure to outdoor air pollution and nighttime primary care visits due to asthma attack. We also investigated the modifying effects of age on this association. METHODS: A case-crossover study was conducted at a primary care clinic in metropolitan Tokyo. The subjects were 308 children aged 0-14 years and 95 adolescents and adults aged 15-64 years. All subjects made visits to the clinic for an asthma attack at between 7 PM and 12 AM. Data on hourly concentrations of particulate matter with a 50% cut-off aerodynamic diameter < OR =2.5 microm (PM(2.5)), ozone, and nitrogen dioxide (NO(2)) were obtained. A conditional logistic regression model was used to estimate odds ratios (ORs) of primary care visits per unit increment of each air pollutant. RESULTS: Among children, the ORs in warmer months per 10 ppb increment of the 24-hour mean concentration of ozone were 1.16 (95% confidential interval [CI], 1.00-1.33) adjusted for temperature, and 1.29 (95% CI, 1.08-1.55) adjusted for PM(2.5), NO(2), and temperature. With respect to modification of the association by age, the ORs for 24-hour mean concentration of ozone--after adjustment for PM(2.5), NO(2) and temperature in warmer months--in children aged 0-1 years, 2-5 years, and 6-14 years were 1.06 (95% CI, 0.63-1.78), 1.37 (95% CI, 1.05-1.71), and 1.25 (95% CI, 0.87-1.82), respectively. There was no association between ozone and primary care visits among adults. CONCLUSIONS: An association was found between ozone and nighttime primary care visits for asthma attack in warmer months; the association was greater among preschool children.

The significance of tumour markers as an indication for mediastinoscopy in non-small cell lung cancer.

OBJECTIVE: The purpose of this study was to verify the significance of tumour markers as indicators for mediastinoscopy in non-small cell lung cancer. METHODOLOGY: In the past 4 years, 205 patients with non-small cell lung carcinoma (NSCLC) underwent surgical resection at Chiba Cancer Center, Chiba, Japan. The correlation between the serum levels of eight tumour markers (CEA, AFP, CA19-9, SCC, NSE, CA125, CYFRA, ProGRP) and the presence of N2 disease was analysed. Univariate and multivariate analyses were performed to determine the relationship between both marker levels and clinical findings and N2 disease. RESULTS: In multivariate analysis, positive CEA was significantly associated with the diagnosis of N2 disease. We also demonstrated that when CA125, CYFRA and ProGRP were positive, they were individually significantly associated with N2 disease. However, CEA was superior to the other markers and equivalent to a combination of various tumour markers. CONCLUSION: It was concluded that evaluation of CEA in addition to CT is of use in the diagnosis of N2 disease in NSCLC patients and should be used as an indication for mediastinoscopy.

Acute effects of ozone exposure on lung function in mice sensitized to ovalbumin.

Pulmonary responses to ozone exposure (1.0 ppm) were investigated in mice sensitized to ovalbumin compared with control mice receiving saline. Pulmonary function parameters were measured by pneumotachography. Arterial blood gases and the concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and tumor necrosis factor-alpha (TNF-alpha) in bronchoalveolar lavage fluid were analyzed. Ozone exposure, when compared with filtered air exposure, caused significantly larger decreases in dynamic compliance (P<0.05) and minute ventilation (P<0.05) in ovalbumin-sensitized mice but not in control mice. Moreover, the decrease in minute ventilation in response to ozone exposure was significantly greater (P<0.01) in ovalbumin-sensitized mice than in control mice. Ozone exposure caused a significant decrease in PaO2 in ovalbumin-sensitized mice but not in control mice. PaO2 after ozone exposure tended to be smaller in ovalbumin-sensitized mice than in control mice. The concentration of sICAM-1 in bronchoalveolar lavage fluid increased in ovalbumin-sensitized mice, but effects of ozone exposure were not observed. These results indicated that sensitization of the immune system to ovalbumin might be a risk factor which aggravates the effects of ozone exposure on the respiratory system.

Effects of air pollution on the prevalence and incidence of asthma in children.

The effects of air pollution on asthmatic symptoms were assessed in a prospective cohort study of 3,049 schoolchildren in 8 different communities in Japan. Respiratory symptoms in these children were evaluated by questionnaires every year from the 1st through the 6th grades. The prevalence of asthma among the 1st graders was strongly associated with a history of allergic or respiratory diseases, but it was not associated with concentrations of air pollution. During the follow-up period, incidence rates of asthma were associated significantly with atmospheric concentrations of nitrogen dioxide. Particulate matter less than 10 microm in diameter (PM10) was also associated with a higher incidence of asthma, although the association was not significant. These findings suggest that air pollution, including nitrogen dioxide, may be an important factor in the development of asthma among children in urban districts.