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.

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.

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.

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.

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.

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.

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.

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.

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.

Diurnal variation in onset of hemorrhagic stroke is independent of risk factor status: Takashima Stroke Registry.

BACKGROUND: We examined the circadian periodicity of hemorrhagic stroke onset to identify any existing specific pattern and its relationship with conventional stroke risk factors using 14-year stroke registration data. METHODS: Data were obtained from the Takashima Stroke Registry, which covers a stable population of approx. 55,000 in Takashima County in central Japan. Out of 499 registered first-ever hemorrhagic stroke events during 1990-2003, there were 429 (186 men, 243 women) events with classifiable onset time. Hemorrhagic stroke incidence was categorized as occurring at night (midnight to 6 a.m.), morning (6 a.m. to noon), afternoon (noon to 6 p.m.) or evening (6 p.m. to midnight). The OR (with 95% CI) of having a stroke in the morning, afternoon or evening were calculated, with night serving as reference. RESULTS: There was significant diurnal variation in hemorrhagic stroke incidence (p < 0.001). The proportion of hemorrhagic strokes was highest in the morning (36.1%, 95% CI: 31.7-40.8) and lowest in the night (11.9%, 95% CI: 9.1-15.3). An excess stroke incidence in the morning was observed in both genders, in subjects < 65 years and > or =65 years, and in both intracerebral hemorrhage and subarachnoid hemorrhage. A second surge was also observed during the later part of the day. The higher daytime risk persisted after adjusting for age, gender, and risk factors. CONCLUSION: In the examination of circadian variation of hemorrhagic stroke onset, a 2-peak temporal distribution was observed, which was independent of conventional risk factors.

The time interval window between stroke onset and hospitalization and its related factors.

OBJECTIVE: Successful acute stroke intervention depends on early hospitalization. The time interval between stroke onset to hospitalization was examined to identify the factors influencing the interval and also to determine whether treatment time window expansion will translate into more treatment. METHODS: Data was obtained from Takashima Stroke Registry covering approximately 55,000 residents in Japan. During 1988-2002, the interval between stroke onset and hospitalization was available for 1,446 registered patients (men 761, women 685). Multivariate regression analyses were performed to evaluate the factors influencing early and late admission. RESULTS: The proportions of the patients who arrived within 3 h of onset were 61.4%. Only 8.7% of the patients arrived during a 3- to 6-hour interval. A substantial proportion (29.9%) of patients arrived after 6 h. Early stroke hospitalization was significantly associated with the severity of the stroke event and time of stroke onset. CONCLUSION: Clinically more severe stroke patients were hospitalized earlier and nocturnal strokes had delayed admission. Even expanding the therapeutic time window from

Stroke case fatality shows seasonal variation regardless of risk factor status in a Japanese population: 15-year results from the Takashima Stroke Registry.

BACKGROUND: Seasonal variation in fatality caused by stroke was examined using 15 years of data from a stroke registry of a Japanese population. METHODS: Data were obtained from the Takashima Stroke Registry, which covers approximately 55,000 residents in central Japan. There were 1,650 registered cases of first-ever stroke between 1988 and 2002. 7- and 28-day fatality rates and 95% confidence intervals were calculated for winter, spring, summer and autumn. After adjusting for gender, age at onset and risk factors, the hazard ratios for fatal strokes in winter, spring and autumn were calculated, with summer serving as the reference. RESULTS: For cerebral infarction, the highest 7- and 28-day fatality rates occurred during spring and winter, where they were more than double the rate during summer. The severest strokes were also more likely to occur during winter and spring. A high spring and winter hazard ratio for 28-day mortality was present in both lacunar and nonlacunar subtypes, in both genders and in subjects < 65 and > or = 65 years of age. No apparent seasonal pattern was observed for cerebral hemorrhage or subarachnoid hemorrhage. The spring and winter excess fatality persisted even after adjusting for age, gender and risk factors. CONCLUSION: Patients who suffer an ischemic stroke during winter or spring have a poorer prognosis. Further investigation is needed to determine the factors that explain this excess risk.

Incidence, admission and case-fatality of acute myocardial infarction: weekend versus weekday in a Japanese population: 16-year results from Takashima AMI Registry (1988-2003).

For acute myocardial infarction (AMI), "weekend" has been associated with higher incidence, admission, and fatality. But, very few studies in this regard are available in Japan. Day of the week variation in AMI was examined using an entire community covering 16-year AMI registration data from Japan. Data were obtained from the Takashima AMI Registry, which covers a stable population of approximately 55,000 in central Japan. There were 379 registered first ever AMI cases with 121 fatal events within 28 days of onset during 1988-2003. We divided the days into two groups: 'Weekend' (Saturday and Sunday) and 'Weekdays' (Monday to Friday). The incidence rate (per 100,000 person-year), admission rate (per 1,000 days) and 28-day case-fatality rates (per 100 events) as well as corresponding rate ratios were calculated with 95% confidence intervals. The distribution of the day of the week for onset, admission and fatality for all subjects was fairly random in our study population; incidence (chi (2) test, P = 0.8), admission (chi (2) test, P = 0.9) and case-fatality (chi (2) test, P = 0.8). The incidence, admission, and case-fatality rates were similar for the 2 day-groups. The incidence rate ratio 1.06 (95% CI: 0.9-1.3), admission ratio 1.03 (95% CI: 0.8-1.3), and case-fatality ratio 1.18 (95% CI: 0.7-1.9) showed no significant risk difference between weekend and weekday. After various adjustments, hazard ratio for weekend AMI in reference to weekday AMI was 1.07 (95% CI: 0.5-2.1). There were no obvious differences in occurrence, hospital admission and acute outcome for AMI patients in the weekday or weekend.

Fibrocartilaginous embolism of the spinal cord diagnosed by characteristic clinical findings and magnetic resonance imaging in 26 dogs.

Fibrocartilaginous embolism (FCE) is a disorder of acute onset that presents with nonprogressive ataxia. We performed a retrospective examination of FCE of the spinal cord diagnosed by characteristic clinical findings and magnetic resonance imaging (MRI) in 26 dogs. In the present study, treatment consisting of physiotherapy alone, or this in combination with corticosteroid administration, was initiated immediately following diagnosis of FCE. Age at onset and the gender ratio in the present study closely correlated with those previously reported. In the present study, 88% of the dogs that developed FCE were small- to medium-sized, which is different from previously reported studies. There is a possibility that FCE also develops relatively frequently in small- to medium-sized dogs. No significant difference was observed between the physiotherapy alone and the physiotherapy and corticosteroids groups of dogs. FCE development has been reported predominantly at the vertebral levels C6-T2 and L4-S3 and less frequently at C1-5 and T3-L3. However, in the present study, FCE developed predominantly at T3-L3. FCE developed at T3-L3 or C1-5 in 69% of the cases in the present study, suggesting that there is relatively frequent development of FCE at these vertebral levels. The recovery time of T3-L3 was the shortest (10.2 +/- 7.4 days), and that of C1-5 was next-shortest (15.8 +/- 5.4) in this study. This suggested the possibility that the detection ratio of cases was low, because the symptoms in cases of FCE that has developed in C1-5 and T3-L3 would have improved before inspection in the secondary institution, where the MRI and diagnosis were performed.

Higher stroke incidence in the spring season regardless of conventional risk factors: Takashima Stroke Registry, Japan, 1988-2001.

BACKGROUND AND PURPOSE: Seasonal variation in stroke incidence was examined using 14-year stroke registration data in a Japanese population. We also examined if this variation was modified by conventional stroke risk factors hypertension, diabetes mellitus, drinking, and smoking. METHODS: Data were obtained from the Takashima Stroke Registry, which covers a stable population of approximately 55,000 in Takashima County in central Japan. There were 1665 (men, 893; women, 772) registered first-ever stroke cases during 1988 to 2001. The average age of stroke onset for men and women patients was 69.4 and 74.2 years, respectively. Incidence rates (per 100 000 person-years) and 95% CI were calculated by gender, age, and stroke subtype for winter, spring, summer, and autumn. After stratifying patients by their risk factor history, the OR (with 95% CI) of having a stroke in autumn, winter, and spring were calculated, with summer serving as a reference. RESULTS: Among the seasons, stroke incidence per 100,000 person-years was highest in the spring (231.3; 95% CI, 211.1 to 251.5). Spring incidence was highest in both men (240.8; 95% CI, 211.5 to 270.2) and women (222.1; 95% CI, 194.4 to 249.9), and in subjects younger than 65 years (72.6; 95% CI, 60.0 to 85.3) and 65 years or older (875.9; 95% CI, 787.5 to 964.3). Among stroke subtypes, spring incidence was highest for cerebral infarction (154.7; 95% CI, 138.2 to 171.2) and cerebral hemorrhage (53.7; 95% CI, 44.0 to 63.4). The spring excess in stroke incidence was observed regardless of the presence or absence of the risk factor histories. CONCLUSIONS: Stroke incidence appears to be highest in the spring among a Japanese population regardless of conventional risk factor history. Factors that explain this excess need further investigation.