Transformation of epidermal growth factor receptor mutated lung adenocarcinoma to small-cell carcinoma long after the cessation of tyrosine kinase inhibitor treatment: A case series and literature review.

Histological transformation to small-cell lung cancer (SCLC) is a well-known mechanism of acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), and almost all patients receive EGFR-TKIs at the time of transformation. We herein report three cases of EGFR-mutated lung adenocarcinoma that transformed into SCLC long after the cessation of EGFR-TKIs. Rapid tumor progression and elevated SCLC marker levels were observed at the time of transformation. Our case highlights the importance of considering SCLC transformation throughout the clinical course. Careful observation of the tumor behavior and SCLC markers should be performed to avoid diagnostic delays.

Granulocyte colony-stimulating factor has the potential to attenuate the therapeutic efficacy of chemo-immunotherapy for extensive-stage small-cell lung cancer.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) has the potential to attenuate the anti-tumor immune responses of T-cells by increasing immune suppressive neutrophils and myeloid-derived suppressor cells. However, the clinical impact of G-CSF on the efficacy of immunotherapy remains unknown. This multi-center retrospective analysis evaluated the impact of G-CSF in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemo-immunotherapy. METHODS: We analyzed 65 patients with ES-SCLC who completed four cycles of induction chemo-immunotherapy and evaluated the effects of G-CSF on progression-free survival (PFS), overall survival (OS), and a durable response to immunotherapy (defined as PFS ≥ 12 months). RESULTS: Fifty patients (76.9%) received ≥ 1 dose of G-CSF. The PFS of the patients with G-CSF was poorer than that of the patients without G-CSF (median PFS 8.3 vs. 4.9 months, p = 0.009). The OS of the patients with G-CSF tended to be shorter, but not statistically significant, than that of the patients without G-CSF (median OS 24.3 vs. 16.4 months, p = 0.137). In the multivariate analysis, G-CSF administration was associated with poorer PFS (hazard ratio 2.78, 95% CI 1.36-5.69, p = 0.005) and was identified as a determinant of a durable response (odds ratio 0.18, 95% CI 0.04-0.80, p = 0.024). These results were consistent with other definitions of G-CSF administration (administration of ≥ 1 dose of pegfilgrastim, or either ≥ 5 doses of filgrastim or ≥ 1 dose of pegfilgrastim). CONCLUSIONS: G-CSF has the potential to attenuate the efficacy of immunotherapy; therefore, the indication for G-CSF during chemo-immunotherapy should be carefully considered for ES-SCLC.

Surgical resection combined with perioperative chemotherapy for a patient with locally recurrent, previously stage IV thymic small-cell carcinoma: A case report.

An 83-year-old Japanese man visited our hospital with dyspnea and general fatigue. Computed tomography (CT) revealed a tumor in the anterior mediastinum, bilateral pleural effusion, pericardial fluid, and multiple liver nodules. We performed a CT-guided tumor biopsy, and the patient was diagnosed with thymic small-cell carcinoma, Masaoka-Koga stage classification IVb. The patient received four cycles of carboplatin and etoposide, and all lesions disappeared on CT. However, after 6 months, CT revealed a recurrent tumor in the anterior mediastinum. After one cycle of rechallenge chemotherapy, we performed extended total thymectomy followed by another three cycles of chemotherapy. More than 2.5 years after the last chemotherapy session, the patient's carcinoma did not recur. Thus, this case suggests that salvage surgery may be a treatment option for local recurrence of thymic carcinoma after complete remission with chemotherapy, even in patients with stage IV cancer.

Pulmonary mycobacteriosis caused by Mycobacterium peregrinum: A case report.

RATIONALE: Mycobacterium peregrinum is a member of the group of rapidly growing nontuberculous mycobacteria. It mainly causes surgical site and catheter-related infections, while pulmonary infection is rare. We herein present a case of pulmonary infection caused by M peregrinum. PATIENT CONCERNS: A 62-year-old woman visited our hospital with dyspnea and was admitted for the treatment of pneumonia in July 2018. DIAGNOSIS: Chest computed tomography showed patchy opacities and consolidation in the bilateral lungs and a cavity in the right upper lobe, which persisted after the treatment of bacterial pneumonia 5 years ago. She was administered ceftriaxone and azithromycin. Consolidation in the bilateral lungs improved, whereas the cavity in the right upper lobe remained and the consolidation surrounding it gradually spread. On admission, the sputum acid-fast bacillus culture was positive, and M peregrinum was identified twice by mass spectrometry. The cavity and consolidation surrounding it were diagnosed as pulmonary mycobacteriosis caused by M peregrinum. INTERVENTIONS: Although we recommended treatment for mycobacteriosis, the patient refused it. OUTCOMES: The patient is regularly followed up; however, the cavity wall is thickening and shadows have become mildly enhanced over the course of 3 years. LESSONS: We herein present a rare case of pulmonary mycobacteriosis caused by M peregrinum and discuss the literature. Since limited information is currently available on pulmonary mycobacteriosis caused by M peregrinum, the accumulation of further case reports and the clarification of its clinical features are needed.

Radiation therapy induces an abscopal effect and upregulates programmed death-ligand 1 expression in a patient with non-small cell lung cancer.

Radiation therapy (RT) activates the antigen presentation of dendritic cells and priming of cancer-specific cytotoxic CD8+ T cells, occasionally resulting in a systemic immune response to the tumor outside of the treatment field. The phenomenon of tumor regression at the site distant from irradiated fields is known as the abscopal effect. Several case reports have indicated a potential role of RT in overcoming primary and acquired resistance against immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) and melanoma patients. We herein report an NSCLC patient who developed acquired resistance to an RT-induced abscopal effect and subsequently experienced reactivation of the systemic antitumor immune response by pembrolizumab, an antiprogrammed death 1 antibody. In this case, RT not only induced an abscopal effect but also upregulated the programmed death-ligand 1 expression outside of the irradiated field when the patient developed resistance to the abscopal effect. This case can facilitate our understanding of the mechanism underlying the RT-induced systemic immune response against cancer cells and adaptive resistance mechanism of cancer cells from immune surveillance. These findings highlight the promising results of current clinical trials combining RT and immune checkpoint inhibitors. Ongoing clinical trials will further establish evidence supporting combination therapy with RT and immune checkpoint inhibitors.

The 21-Year Trend of Stroke Incidence in a General Japanese Population: Results from the Takashima Stroke Registry, 1990-2010.

INTRODUCTION: Since the 1960s, the stroke morality rate in Japan has declined significantly. Although several risk factors for stroke have become more evident due to increasingly Westernized lifestyle, there have been no population-based registry data on recent time trends in stroke incidence in Japan. The purpose of this study is to determine these trends in stroke incidence using a population-based registry. METHODS: Data were obtained from the Takashima Stroke Registry, which covers approximately 50,000 residents in Takashima City, Japan. The age- and sex-standardized stroke incidence rate was estimated using the direct method. Average annual relative changes of stroke incidence were estimated using Poisson regression models. RESULTS: We identified a total of 2,371 patients with first-ever stroke during the period 1990-2010. Crude incidence rates of total stroke (per 100,000 person-years) were 225 in the early period (1990-2001) and 187 in the late period (2002-2010), and the mean age at onset of stroke increased from 71.9 years in the early period to 74.8 years in the late period. Age- and sex-standardized incidence rates of stroke (per 100,000 person-years) decreased from 327 in the early part of this study period and 206 in the later period. During the 21-year period, age- and sex-standardized average annual relative reduction in stroke incidence was statistically significant (-3.7% per year). When stratified into early and late periods, the adjusted annual relative reduction in stroke incidence was observed during the early period (-2.1% per year), and there were no significant changes during the late period. CONCLUSIONS: In this population-based registry, there was a significant reduction in incidence of stroke from 1990 to 2010. Although the speed of reduction in stroke incidence appears to have slowed down after 2000, continuous public health measures are required to provide further protection against stroke.

Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 1): Rate of Crystallization from Cream Containing 20% (w/w) Urea and Evaluation of the Properties of the Deposit.

Two creams containing 20% (w/w) urea and various emulsifiers, a nonionic surfactant (NS) and lecithin (LEC), were prepared, and the rate of crystallization following application of the cream and differences in the properties of the deposits were investigated. Post-application crystallization was slower with the LEC formulation. Differences in the crystals obtained from the two formulations and from a 20% aqueous solution of urea were evaluated by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), powder X-ray-DSC (PXRD-DSC) and Fourier transform infrared spectrophotometry (FT-IR). PXRD and PXRD-DSC measurements showed that the diffraction patterns of both formulations differed from that of urea. The NS formulation provided diffraction peaks for urea and a urea composite, whereas only the urea composite was evident in the LEC formulation. DSC scans of urea showed an endotherm at around 134°C, whereas the deposits from both formulations provided an endotherm 23-25°C below that of urea; the NS formulation also showed a peak at around 140°C. These results indicate a tendency for urea crystallization in the NS formulation. FT-IR measurements showed that both deposits have a urea-based structure. The effects of the LEC formulation components on the physical properties of urea were investigated by PXRD and showed that all diffraction peaks were evenly weakened, suggesting that urea tends to be amorphous and that the formulation impacts post-application urea crystallization. Consequently, the amorphous state of urea can be maintained post-application by optimizing the formulation, thereby increasing the clinical efficacy of the cream.

Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 2): Novel Analytical Methods of Urea Accumulated in the Stratum Corneum by Tape stripping and Colorimetry.

The transfer of urea from a urea formulation to the stratum corneum varies with the formulation base and form, and impacts the formulation's therapeutic effect. Consequently, determining the amount of urea transferred is essential for developing efficient formulations. This study assessed a simple method for measuring the amount of urea accumulated in the stratum corneum. Conventional methods rely on labeling urea used in the formulation with radiocarbon ((14)C) or other radioactive isotopes (RIs), retrieving the transferred urea from the stratum corneum by tape stripping, then quantitating the urea. The handling and use of RIs, however, is subject to legal regulation and can only be performed in sanctioned facilities, so methods employing RIs are neither simple nor convenient. We therefore developed a non-radiolabel method "tape stripping-colorimetry (T-C)" that combines tape stripping with colorimetry (urease-glutamate dehydrogenase (GLDH)) for the quantitative measurement of urea. Urea in the stratum corneum is collected by tape stripping and measured using urease-GLDH, which is commonly used to measure urea nitrogen in blood tests. The results indicate that accurate urea measurement by the T-C method requires the application of 1400 mg (on hairless rats) of a 20% urea solution on a 50 cm(2) (5×10 cm) area. Further, we determined the amount of urea accumulated in the stratum corneum using formulations with different urea concentrations, and the time course of urea accumulation from formulations differing in the rate of urea crystallization. We demonstrate that the T-C method is simple and convenient, with no need for (14)C or other RIs.

Deposits from Creams Containing 20% (w/w) Urea and Suppression of Crystallization (Part 3): Novel Analytical Methods Based on Raman Spectroscopy for the Characterization of Deposits and Deposition Phenomena of Creams Containing 20% (w/w) Urea.

In drug formulations for external application, variations in the state of pharmaceutical agents within the base formulation may affect the transfer of agents to the skin. Here, we use Raman spectroscopic methods to acquire more detailed information on the state of the active pharmaceutical ingredients within an externally applied formulation. The combination of wide-field Raman spectroscopy with an experimental method in which drug formulations are applied to glass surfaces provided a new method for characterizing the state of pharmaceutical agents within drug formulations. Here, we demonstrate the usefulness of this new method, called application to glass-wide-field Raman spectroscopy (AG-WRS). In addition to allowing rapid and easy wide-field observations, the use of WRS allows Raman imaging in a manner that is insensitive to variations in the thickness of the formulations applied to sample slides. We consider two types of urea-compound creams with different crystal deposition rates, using AG-WRS to characterize the post-application time-evolving state of deposited crystals. Differences in the base pharmaceutical produce different spectra for the deposits, indicating that the deposits differ in composition and structure. In addition, we use microscopic laser Raman measurements to demonstrate that the process of crystal formulation differs significantly for formulations with different compositions. Our results demonstrate that the combination of AG-WRS with existing analytical techniques such as powder X-ray diffraction or thermal analysis yields more detailed and timely post-application information on the state of pharmaceuticals in external application. We believe this will be a valuable analytical tool for future studies related to the development of external application.

Acute case-fatality rates of stroke and acute myocardial infarction in a Japanese population: Takashima stroke and AMI registry, 1989-2005.

BACKGROUND: Few comprehensive stroke and acute myocardial infarction registries of long duration exist in Japan to illustrate trends in acute case-fatality of stroke and acute myocardial infarction with greater precision. We examined 17-year case-fatality rates of stroke and acute myocardial infarction using an entire community-monitoring registration system to investigate trends in these rates over time in a Japanese population. METHODS: Data were obtained from the Takashima Stroke and AMI Registry covering a stable population of approximately 55 000 residents of Takashima County in central Japan. We divided the total observation period of 17 years into four periods, 1989-1992, 1993-1996, 1997-2000, and 2001-2005. We calculated gender, age-specific and age-adjusted acute case-fatality rates (%) of stroke and acute myocardial infarction across these four periods. RESULTS: During the study period of 1989-2005, there were 341 fatal cases within 28 days of onset among 2239 first-ever stroke events and 163 fatal cases among 433 first-ever acute myocardial infarction events. The age-adjusted acute case-fatality rate of stroke was 14·9% in men and 15·7% in women. The age-adjusted acute case-fatality rate of acute myocardial infarction was 34·3% in men and 43·3% in women. The age-adjusted acute case-fatality rates of stroke and acute myocardial infarction showed insignificant differences across the four time periods. The average annual change in the acute case-fatality rate of stroke (-0·2%; 95% CI: -2·4-2·1) and acute myocardial infarction (2·7%; 95% CI: -0·7-6·1) did not change significantly across the study years. CONCLUSIONS: The acute case-fatality rates of stroke and acute myocardial infarction have remained stable from 1989 to 2005 in a rural and semi-urban Japanese population.

Genetic variants of the fatty acid desaturase gene cluster are associated with plasma LDL cholesterol levels in Japanese males.

Fatty acid (FA) compositions in tissues are related to metabolic disorders, and consequently the appropriate management of underlying FA compositions in tissues is considered to be important. However, the relationship among the serum lipid profiles, the FA composition of the red blood cell (RBC) membranes and genetic variations in the fatty acid desaturase (FADS) genes in Japanese men is unclear. In this study, the subjects recruited were 137 Japanese men, 40 to 60 y old, who had a regular health checkup. Their serum lipid profile and the relative FA composition of the RBC membranes were measured. They were genotyped for the single nucleotide polymorphisms (SNPs) rs174553, rs174546, rs99780 and rs174583 in FADS gene. Multiple regression analysis was conducted to detect the relationship among hyperlipidemia, the FA composition of the RBC and the FADS genotypes. As a result, the homozygous genotype for the minor alleles in rs174553, rs174546, rs99780 were found to be associated with lower low-density lipoprotein cholesterol (LDL-C) levels and a lower LDL-C/total-cholesterol ratio. The homozygous genotype for the minor alleles reduced the risk of high LDL-C level (R2=0.50, ß=-0.20, p=0.009), whereas, the arachidonic acid (AA) levels in the carriers of the homozygous genotype for the minor alleles tended to be lower compared with the carriers of the major alleles. However, no significant differences were observed in any FA level among the three genotypes for four SNPs. These results indicate that the appropriate management of serum LDL-C levels depending on genetic predisposition in FADS genotypes should be encouraged.

Wake-up stroke: incidence, risk factors and outcome of acute stroke during sleep in a Japanese population. Takashima Stroke Registry 1988-2003.

Characterization of the time of stroke onset has been plagued by the problem of determining the time of the onset of events that are detected when the patient awakens. Our aim was to evaluate the characteristics, risk factors and acute fatality associated with wake-up stroke. Data was obtained from Takashima Stroke Registry covering approximately 55,000 residents in central Japan. During the period 1988-2003, information about the situation at stroke onset was available for 897 cerebral infarction (CI) and 335 intracerebral hemorrhage (ICH) events. Differences in characteristics and outcome between stroke during sleep and stroke while awake were explored. Among CI and ICH cases, 9.7 and 11.9% suffered from stroke during sleep, respectively. Hypertension and experiencing a severe event were associated with stroke during sleep among CI. Smoking and experiencing a severe event were associated with stroke during sleep and a drinking history reduced the chance of stroke during sleep among ICH. Acute fatality risks did not differ between stroke during sleep and stroke while awake among both CI and ICH cases. About 1 in 10 stroke patients had an onset of stroke during sleep. Hypertensive, smoker and clinically more severely affected patients had a higher prevalence of stroke during sleep. There were no differences between the 2 groups with respect to acute-case fatality.

Ambient air pollutants and acute case-fatality of cerebro-cardiovascular events: Takashima Stroke and AMI Registry, Japan (1988-2004).

BACKGROUND: Apart from the conventional risk factors, cerebro-cardiovascular disease (CVD) are also reported to be associated with air pollution, thus lowering the level of exposure might contribute in prevention activities to reduce the associated adverse outcomes. Though few studies conducted in Japan have reported on the CVD mortality but none have explored the effect of air pollutant exposure on the acute case-fatality of CVD. We investigated the effects of air pollution exposure on acute case-fatality of stroke and acute myocardial infarction (AMI) in a setting where pollutant levels are rather low. METHODS: We leveraged the data from the Takashima Stroke and AMI Registry, which covers a population of approximately 55,000 in Takashima County located in central Japan. The study period of 6,210 days (16 years, leap years also taken into account) were divided into quartiles of daily average pollutant concentration; suspended particulate matter (SPM), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)), and photochemical oxidants (Ox). The stroke and AMI events were categorized to corresponding quartiles based on the pollution levels of the onset day. To study the effects of air pollutants, we estimated the fatality rate ratio across quartiles of the pollutants where the lowest quartile served as the reference. RESULTS: There were 307 (men: 153 and women: 154) fatal stroke cases within 28 days of onset among the 2,038 first ever stroke during 1988-2004. In the same period, there were 142 (men: 94 and women: 54) fatal AMI cases within 28 days of onset among the 429 first ever AMI events. The mean of the measured pollutant levels were as follows: SPM 26.9 µg/m(3), SO(2) 3.9 ppb, NO(2) 16.0 ppb, and Ox 28.4 ppb. Among the pollutants, higher levels of NO(2) showed increased fatality risk. In multi-pollutant model, the highest quartile of NO(2) was associated with 60% higher stroke case-fatality risk in comparison to lowest quartile of NO(2). In the fully adjusted model the fatality-rate ratio was 1.65 (95% CI 1.06-2.57). This association was more prominent among stroke subtype of cerebral infarction. Other pollutant levels did not show any association with stroke or AMI case-fatality. CONCLUSION: We observed association between NO(2) levels, an index of traffic related air pollution, with the acute case-fatality of stroke, especially cerebral infarction in our study population. Further studies are needed in different regions to determine the association between ambient air pollutants and acute cardiovascular fatalities.

Short-term exposure to air pollution and incidence of stroke and acute myocardial infarction in a Japanese population.

BACKGROUND: Exposure to high levels of air pollution can increase the risk of cardiovascular events. However, there is no clear information in Japan on the effect of pollution on the incidence of stroke and acute myocardial infarction (AMI). Therefore, we investigated the effects of air pollution on the incidence of stroke and AMI in a setting where pollutant levels are rather low. METHODS: Data were obtained from the Takashima Stroke and AMI Registry, which covers a population of approximately 55,000 in Takashima County in central Japan. We applied a time-stratified, bidirectional, case-crossover design to estimate the effects of air pollutants, which included suspended particulate matter (SPM), sulfur dioxide (SO(2)), nitrogen dioxide (NO(2)) and photochemical oxidants (Ox). We used the distributed lag model to estimate the effect of pollutant exposure 0-3 days before the day of event onset and controlled for meteorological covariates in all of the models. RESULTS: There were 2,038 first-ever strokes (1,083 men, 955 women) and 429 first-ever AMI cases (281 men, 148 women) during 1988-2004. The mean pollutant levels were as follows: SPM 26.9 µg/m(3); SO(2) 3.9 ppb; NO(2) 16.0 ppb, and Ox 28.4 ppb. In single-pollutant and two-pollutant models, SO(2) was associated with the risk of cerebral hemorrhage. Other stroke subtypes and AMI were not associated with air pollutant levels. CONCLUSIONS: We observed an association between SO(2) and hemorrhagic stroke; however, we found inconclusive evidence for a short-term effect of air pollution on the incidence of other stroke types and AMI.

Admission with metabolic disorder is a useful predictor of the 1-year prognosis for patients with unstable angina, but not for patients with acute myocardial infarction: east-Osaka acute coronary syndrome registry.

BACKGROUND: For patients with acute myocardial infarction (AMI), several studies have examined the relationship between the metabolic syndrome and prognostic outcome. However, few studies have revealed an association between the metabolic syndrome and clinical outcomes in patients with unstable angina (UA). This study compared the differences in the usefulness of recognizing metabolic disorders for the prediction of a 1-year prognosis in patients with UA and AMI. METHODS: The study cohort consisted of 1173 patients with a mean age of 67 years. The focus was on general prognostic factors and five metabolic disorders (body mass index; hypertension; blood glucose/diabetes mellitus; and, serum concentrations of triglycerides and high-density lipoprotein cholesterol) at the time of admission. RESULTS: According to multivariate logistic regression analysis, metabolic scores on admission positively related to 1-year mortality or major adverse cardiovascular events (MACE) for patients with UA, but not for those with AMI, with an increase in either all-causes mortality or MACE being associated with the degree of metabolic dysfunction. No other general prognostic factors were related to either 1-year mortality or MACE in patients with UA. By contrast, general prognostic factors such as age and the Killip classification had a positive effect on 1-year mortality or on MACE for the patients with AMI. CONCLUSION: Accumulation of the effects of each metabolic disorder may affect mortality and MACE for patients with UA.

Time lag to hospitalisation and the associated determinants in patients with acute myocardial infarction: the Takashima AMI Registry, Japan.

BACKGROUND: Prompt initiation of treatment is the cornerstone in the management of patients with acute myocardial infarction (AMI). The time lags for AMI hospitalisations were examined to identify the factors influencing the interval. METHODS: Time lag information was available for 273 men and 148 women from the Takashima AMI Registry during 1988-2006. Multivariate regression analyses were performed to evaluate the factors influencing early and late admission. RESULTS: The median time to hospitalisation was 2 h (mean 6.1, SD 18.7). Within 2 h of onset, 59.8% patients arrived and 20.6% arrived during the 2-6 h interval. A substantial number of patients (19.6%) arrived after 6 h and onwards. A time lag of >2 h in hospital admission was significantly influenced by history of hypertension, angina, presence of syncope as an initial symptom and time of AMI onset. A time lag of >6 h shared similar characteristics except for presence of history of angina. CONCLUSIONS: About one-fifth of patients with AMI have prolonged time lag in the study population. Future research intervention and health promotion activities should focus on achieving a reduction in presentation delays.

Ischemic stroke subtypes in a Japanese population: Takashima Stroke Registry, 1988-2004.

BACKGROUND AND PURPOSE: Population-based information on the epidemiology of ischemic stroke (IS) subtypes is scant. In this study, we characterized IS subtypes in terms of incidence, time trend, and risk factor profiles in a community-based population. METHODS: We obtained data from the Takashima Stroke Registry on approximately 55 000 residents of Takashima County in central Japan and calculated age-adjusted stroke incidence rates for different IS subtypes. We determined the incidence time trend by calculating the average annual change across years and also compared risk factors between subtypes. RESULTS: There were 1389 first-ever ischemic strokes registered during 1988 to 2004. Lacunar infarction was the most frequent etiology (54.1%) followed by cardioembolic infarction (22.9%). Age-adjusted incidence rates for different IS subtypes were lacunar, 77.1; cardioembolic, 31.5; and nonlacunar, 29.7/10(5) person-years. The average annual change was not significant for the IS subtypes except for nonlacunar infarction, which showed a decreasing trend. Risk factor analysis showed that patients with lacunar infarctions were younger and less likely to have a history of transient ischemic attack or a drinking habit than patients with nonlacunar infarctions. CONCLUSIONS: Lacunar infarct was the most common IS subtype in our population. We found no significant change in the incidence of subtypes during the study, except a decrease in nonlacunar infarction.

Brachial-ankle pulse wave velocity predicts all-cause mortality in the general population: findings from the Takashima study, Japan.

Brachial-ankle pulse wave velocity (baPWV) is a relatively new non-invasive measure of arterial stiffness obtained using an automated system. We assessed the relationship between baPWV and 6.5-year overall mortality from the Takashima cohort study. The baPWV was measured in 2642 participants at baseline. When participants were divided into tertiles, all-cause mortality increased significantly as baPWV increased (P<0.001). Participants in the highest baPWV tertile showed an increased risk of all-cause mortality evidenced by a multivariable adjusted hazard ratio of 6.8 (95% confidence interval: 1.4-32.8) as compared with the lowest tertile. The present study demonstrated that increased baPWV is an independent predictor of all-cause mortality in the Japanese population.

Association of lifestyle factors, polymorphisms in adiponectin, perilipin and hormone sensitive lipase, and clinical markers in Japanese males.

According to recent genome-wide association studies, a number of single nucleotide polymorphisms is reported to be associated with diseases or several clinical markers. Among them, adiponectin (ADIPOQ) and perilipin (PLIN) polymorphisms are major factors of obesity. However, the association between lifestyle factor, these polymorphisms and obesity-related clinical markers in Japanese is not well researched. Therefore, the aim of present study is to investigate the association between lifestyle factor, polymorphisms of lipid metabolic genes, and clinical markers in 148 middle-aged Japanese males. The study revealed that ADIPOQ 45 T>G and ADIPOQ 276 G>T genotypes were significantly associated with triglyceride, total cholesterol, hemoglobin A1c (HbA1c) in blood and body mass index (BMI). PLIN4 11482 G>A and hormone sensitive lipase (LIPE)-60 C>G genotypes were respectively associated with BMI and serum triglyceride. Not only genetic factors but also lifestyle factors influence several clinical markers. The BMI of subjects who like sweets and have the GG allele in ADIPOQ 276 G>T was higher than that of subjects who don't like sweets. The habit of eating fruits and fish affected low-density lipoprotein-cholesterol of the GT allele and HbA1c of the TT allele in ADIPOQ 276 G>T. Those findings indicate improvement and conservation of lifestyle depending on genetic predisposition in ADIPOQ, PLIN and LIPE should be encouraged.

Circaseptan variation in case-fatality rate for patients with acute subarachnoid hemorrhage (Takashima Stroke Registry 1988-2003).

We explored the circaseptan variation in 28-day case-fatalities for patients with subarachnoid hemorrhage (SAH) across days of the week. Data were obtained from the Takashima Stroke Registry, which covers approximately 50000 residents of central Japan. There were 169 first-ever SAH cases registered during the period 1988-2003 (68 in males, 101 in females). We divided the SAH cases into two groups according to the day on which the SAH occurred: "weekend" and "weekday". The 28-day case-fatality rate and 95% confidence interval (CI) were calculated. Multiple logistic regression analysis was used to calculate the adjusted odds ratio (95% CI) for weekday fatalities by entering all relevant patient-level variables into the model. The 28-day case-fatality rate for SAH was higher on weekdays (51.7%) than on weekends (32.6%; odds ratio 2.19; 95% CI: 1.10-4.49). The differences in fatality rate persisted after adjustment for age, sex, severity, family history of stroke and patient history of hypertension, diabetes mellitus, dyslipidemia, drinking and smoking. We observed a circaseptan variation in fatalities from SAH, with higher fatality rates during weekdays in our study population.