To compare the patterns of uveitis, emphasizing similarities and discrepancies, in the Middle East and Europe.Six articles reporting uveitis patterns from the Middle East including a total of 2,693 cases, and seven articles with a sum of 4,379 cases from Europe were analyzed and patterns in each region were defined and compared.In both regions, uveitis was most commonly seen in the fourth decade of life with anterior uveitis being the most common anatomical form. Idiopathic cases accounted for the majority of anterior and intermediate uveitis; toxoplasmosis was the most frequent entity in posterior uveitis while Behcet’s disease and idiopathic forms were the next most common causes in the Middle East and in Europe, respectively.Since patterns of uveitis differ in various geographic regions, discovering these patterns would be helpful for the diagnosis and treatment of this broad category of conditions. This necessitates applying a universal diagnostic classification system to enable accurate comparisons. Uveitis accounts for 5–20% of legal blindness in Europe and the United StatesDue to the varying prevalence of infectious (e.g. tuberculosis and toxoplasmosis) and non-infectious (e.g. Behçet’s disease) entities in different parts of the world, one would expect variability in the prevalence and patterns of uveitis. This variability may be influenced by multiple factors including race and genetic background, environmental factors, referral patterns, and diagnostic criteria and facilities. For instance, in the US, the four most common forms of uveitis include acute anterior uveitis associated with ankylosing spondylitis, sarcoidosis, cytomegalovirus retinitis, and toxoplasmosis.8In the Indian subcontinent, toxoplasmosis, VKH syndrome, and idiopathic anterior uveitis are most frequently observed.11The purpose of this study was to compare patterns of uveitis in Europe with that in the Middle East, and to highlight similarities and disparities.Six articlesExcept for the Finnish studyHaving been classified as an idiopathic and independent disease in some articles, all cases of pars planitis were considered as idiopathic for uniformity. An article from IsraelTo present data, we used mean ± standard deviations (SDs) and frequencies (percentage). To compute these values we used weighted means proportional to sample size of a particular paper. Whenever there was no information about a particular item, we disregarded that particular data. All statistical analyses were performed using SPSS software version 17.0 .Mean age of participants in Middle Eastern and European studies was 35.2 and 39.1 years, respectively. Male subjects comprised 52% of cases in Middle Eastern and 49.4% of subjects in European studies. There was no significant difference in terms of age and sex between Middle Eastern and European studies; both study groups reported the fourth decade of life as the most common age for presentation of uveitis .In studies from the Middle East, the most common anatomical forms, in descending order, were anterior (49.6%), pan- 24.9%), posterior (15.5%), and intermediate uveitis (10.3%); however, in the Ankara study.9%, postIn Middle Eastern studies, idiopathic uveitis (49.9%) was the most common form of anterior uveitis while Behçet’s disease 13.7%), Fuchs heterochromic iridocyclitis (FHIC) (8.6%), herpes viruses (10.6%), TB (1.9%), and HLA B-27 associated disease , Behçet’s disease 17.4%), idiopathic 16%), Eales disease (4.4%), toxocariasis (3.9%), acute retinal necrosis (3.6%), TB (2.8%), sympathetic ophthalmia (1.9%), and VKH syndrome (1.7%). Highly prevalent conditions were Behçet’s disease in the Ankara (26.3%)%, Eales .4%, idioIn Middle Eastern studies, Behçet’s disease (44.8%) was the most common cause of panuveitis followed by idiopathic 22.2%), VKH (10.9%), multifocal choroiditis panuveitis (MCP) (3.8%), toxoplasmosis and sympathetic ophthalmia (3.6%), and sarcoidosis (3.4%). Behçet’s disease was frequent in Turkey (53.8%).2%, VKH In Middle Eastern studies, idiopathic intermediate uveitis (82.7%) was most common followed by sarcoidosis (4%), multiple sclerosis (2%), TB (1.6%), and Behçet’s disease (1.2%). Noteworthy percentages were reported for sarcoidosis in Iran (7.3%)Regardless of anatomical classifications and considering all causes of uveitis as a whole, in Middle Eastern studies, idiopathic uveitis was found to be most common (41.6%) followed by Behçet’s disease 17.6%), toxoplasmosis (6.3%), herpes viruses (5.5%), FHIC (4.3%), VKH (2.9%), TB (2.8%), HLA B-27 associated disorders (1.9%), sympathetic ophthalmia (1.2%) and sarcoidosis (1.1%). Herpes viruses (11.9% and 16%) and TB (7.6% and 10.5%) were rather frequent in both Saudi Arabian studies.6%, toxoIn both Middle Eastern and European studies, toxoplasmosis, herpes viruses, and TB were major infectious agents; they were found in 6.3%, 5.5%, and 2.8% of Middle Eastern and in 9.1%, 6.0%, and 1.9% of European cases, respectively. Remarkably frequent non-infectious causes were Behçet’s disease, FHIC, sarcoidosis, and VKH with prevalence rates of 17.6%, 4.3%, 1.1%, and 2.9% in the Middle East, and 2.9%, 4.9%, 1.4%, and 1.2% in Europe, respectively.Limitations of epidemiological studies on uveitis stem from a variety of factors including heterogeneity of diagnostic criteria and work-up, lack of uniform classification systems or precise definitions, and the effects of referral and selection bias. These factors render comparison of epidemiological studies from different regions and populations difficult.Most uveitis studies convey data obtained from tertiary referral centers rather than population-based information. More complicated and severe forms of pan- and posterior uveitis may be over-represented at referral centers; in contrast, primary care and population-based studies tend to report less severe cases such as anterior uveitis.Average age and male to female ratio did not differ significantly between Middle Eastern and European studies .The most frequent anatomic forms, in order of frequency, were anterior, pan-, posterior and intermediate uveitis in Middle Eastern studies (except for the Ankara studyConsidering anterior uveitis, idiopathic cases were comparable in Middle Eastern and European studies and were the most prevalent category in all studies. Behçet’s disease in TurkeyRegarding posterior uveitis, in the Middle East, toxoplasmosis was the most frequently reported cause in IranConcerning panuveitis, in Middle Eastern studies, Behçet’s disease was consistently the most frequent cause in IranIn terms of intermediate uveitis, idiopathic cases held the largest share in both European and Middle Eastern reports. Eye-catching prevalence rates were noted for sarcoidosis in IranOverall, in both geographic regions, idiopathic uveitis was the most common form of intraocular inflammation; in the Middle East, Behçet’s disease and toxoplasmosis, and in Europe, toxoplasmosis and herpes viruses ranked second and third. Behçet’s disease, VKH and sympathetic ophthalmia were more common in the Middle East while toxoplasmosis and HLA-B27 associated disorders were more frequent in Europe. Considering infectious causes, toxoplasmosis in Europe and TB in the Middle East were relatively more prevalent but herpes viruses did not show any prominent differences in prevalence.Since uveitic entities follow different patterns in different regions and are influenced by a variety of factors, epidemiologic studies can help improve their diagnosis and treatment. Adoption of a universal classification systems and population-based studies in all countries may provide more reliable data for comparisons among different areas.


Obesity is common in type 2 diabetic patients in some of the Middle Eastern countries, which are amongst the countries with highest rates of diabetes mellitus and obesity.We conducted this study to assess the prevalence of obesity in Yemeni patients with type 2 diabetes mellitus.Body mass index (BMI) of patients with type 2 diabetes mellitus who were 25-years-old or older was measured during their first visit to an endocrinology and diabetes clinic in Sana’a, Yemen over a 4-year period from May 2007 to May 2011.2), overweight (BMI 25-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2), respectively. On the other hand, 256 (28%), 369 (40.0%), and 294 (32%) of the female patients were non-obese (BMI < 25 kg/m2), overweight (BMI 25-29.9 kg/m2), and obese (BMI ≥ 30 kg/m2), respectively.The BMI was measured in 1640 patients  who attended the clinic. According to the measured BMI, 328 (45.5%), 314 (43.5%), 79 (11%) of the male patients were non-obese (BMI < 25 kg/mThe prevalence of obesity in patients with type 2 diabetes mellitus in Yemen is high with respect to the Yemeni population, especially in females. Obesity is prevalent in patients with type 2 diabetes mellitus (type 2 DM). In some areas such as the United Kingdom, approximately 86% of patients with type 2 DM are overweight or obese . In AustThe aim of this study was to assess the prevalence of overweight and obesity among Yemeni patients with type 2 DM aged ≥ 25 years on their first visit to the endocrine and diabetes clinic. In addition, we aimed to reveal its association with age of the patients, and the duration of the disease.The Yemeni patients with type 2 DM who attended a specialized diabetes and endocrinology clinic since May 2007 through May 2011 were recruited in the study. Patients of non-Yemeni origin were excluded from the study. BMI (the weight in kilogram divided by height in square meter) was calculated for all patients at the first visit. All the participants had ≥ 25 years of age. According to the BMI, the patients were allocated into 5 groups . The analysis was performed on all patients admitted to the study. Continuous variables were summarized by descriptive statistics, using means and standard deviation (SD), and the difference was measured by t test. Confidence intervals (95% CI) were calculated in order to indicate precision of the sample estimation, variability of the characteristics, and the degree of confidence being studied. Median values and interquartile range (IQR 25-75%) were also used to show the central tendency; its upper and lower quartiles as a preferred measure of range were used with skewed distribution. Categorical variables were expressed as numbers and percentages and the difference was examined by the chi-square test. Pearson correlation coefficient and its P value were used to assess the correlation between variables. All statistical analyses were two-sided, using a pre-specified 5% significance level, i.e. significance was defined as P value < 0.05. Analysis was performed using SPSS software, version 18.0 for windows .A total of 1640 Yemeni patients with 25 years of age or older attended to the clinic over a four-year period. All of them were recruited in the study. The median (IQR) duration of DM was 3.0 (0.1-8.0) years and the mean duration was 5.0 ± 6.0 years (95% CI: 4.65-5.27). The mean age of the study population was 50.3 ± 11.5 years, (96% CI: 49.7-50.9). 2 and 276 (28.8%) patients were obese (BMI ≥ 30 kg/m2).Most of the patients presented with recently diagnosed DM. the duration of the disease since the time of diagnosis was less than five years, five to ten years, ten to 15 years, and more than 15 years in 980 (59.7%), 312 (19%), 196 (12%), and 152 (9.3%) patients, respectively. Among the patients, 959 (58.5%) had a BMI ≥ 25 kg/m2 and 25.4 kg/m2, respectively (P < 0.001). The basic characteristics of the study population is shown in 2) than in males (25.4 ± 3.9 kg/m2) (P < 0.001).2 = 7.0, P = 0.008). Among those with normal weight , there were 299 (41.5%) out of 721 males and 240 (26.1%) out of 919 females . In the overweight group (BMI of 25-29.9 kg/m2), 314 (43.6%) out of 721 were males and 369 (40.2%) out of 919 were females . In the group with mild obesity (BMI of 30-34.9 kg/m2), there were 205 (22.3%) out of 919 females 71 (9.8%) out of 721 males . In the group with moderate obesity (BMI ≥ 35), we also found a much higher rate of obesity among the females than males with the frequency of 89 (9.7%) out of 919 and 8 (1.1%) out of 721 patients, respectively .There was a significant difference between the mean BMI for females and males in all age groups. The peak differnce in the mean BMI between females and males was in those aged 45-54. There were significant sex differences with regard to the BMI distributions in patients with type 2 DM. In patients with a low or normal BMI, we found a male preponderance. Among the group with a BMI < 19, there were 29 (4.0%) males out of 721 and 16 (1.7%) out of 919 were females  for exploring the association between BMI and each patient’s age and duration of DM. We also tested the association between duration of DM and glycemic control expressed as HbA1c levels. There was a significant inverse correlation between BMI and age , between BMI and duration of DM  These results declared that the BMI values tended to be significantly lower with advanced age and increased duration of diabetes.2 in patients with type 2 DM was approximately 58.5% and 28.8% of them were obese (BMI ≥ 30 kg/m2). The sex-specific and age-specific mean BMI values were significantly higher in females than in males across different age groups with the peak difference between 45 to 54 years of age. Most of our patients in our study were recently diagnosed. In this study, the prevalence of BMI ≥ 25 kg/m2) in females was three times higher than males with type 2 DM (32% vs. 11%). This female-male difference was even higher than the rate reported from Saudi Arabia (87.7% vs. 83.1%)  . Therefo2), prevalence rate in women was about nine times higher than in males , which seemed to be higher than any female-male difference in neighboring countries. Many factors have been shown to be associated with an increased risk of obesity and DM such as high intake of sugar-sweetened beverages  were prevalent in patients with type 2 DM in Yemen, with a higher frequency in females than in males. Moreover, the mean BMI, as a continuous variable associated with morbidity and mortality, was significantly higher in females than in males at different age groups. The finding of poor glycemic control among the majority of patients was another alarming sign of low quality diabetes care in this country. We recommend improving the standards of diabetes health care in Yemen at the primary and critical care levels in order to reduce the burden attributable to the DM in the Yemen.


Age >60 years was the major risk factor for death from pandemic (H1N1) 2009.Pandemic (H1N1) 2009 affected Chile during the winter of 2009. The hospitalization rate was 0.56% overall and 3.47% for persons  On April 23, 2009, the World Health Organization issued alerts about the emergence of pandemic (H1N1) 2009. On May 17, during fall in the Southern Hemisphere, the first case of this disease in Chile was identified  2009 confirmed by PCR in a pilot study.ILI was defined as fever >38.5°C and cough plus All fatal cases included in the analysis occurred in persons whose deaths were directly attributable to influenza. Demographic data, clinical features, concurrent conditions, and number of consultations before hospitalization were recorded  were 80% of ILI cases reported to the Ministry of Health during the study. We conducted statistical analysis by using SPSS version 13.0  and Epi Info version 6 .>60 years of age. During the same period, 651,416 treatments with oseltamivir were reported. Treatment data indicated that the attack rate was 4%.During May 19–August 3, 2009, a total of 342,588 ILI cases were reported. Median age of case-patients was 20.4 years (range <1–109 years). The overall attack rates were 1.2% for pandemic (H1N1) 2009 and 0.4% for persons >60 years of age and 1.6% for children <5 years of age) , and 52% were women. Overall rate of hospitalization was 9.4/100,000 persons. Case-hospitalization rate was 0.6% (3.5% for persons  of age) . Pneumon>49 years of age. CFR was 0.04%: the highest rate was for patients >60 years of age , followed by persons 15–59 years of age (0.045%). CFR was 0.02% for children <5 years of age and 0.008% for children 5–14 years of age . Among these patients were 117 who died during the study period. Median age was 47 years (range 4 months–89 years) for persons who died and 30 years (range <1–94 years) for persons who survived (p<0.0001). Forty-seven percent of patients who died were s of age . Fifty p>60 years of age and <5 years of age were at a higher risk for severe disease, and patients >60 years of age were at a higher risk for death. At least 1 concurrent condition was identified as a risk factor for death from pandemic (H1N1) 2009. Eighty-four (87.5%) of 96 patients who died and 485 (54.3%) of 893 of patients who survived had an underlying disease . A concurrent condition was a risk only for persons 15–49 years of age  for persons who died and 3.6 days (range 0–20 days) for persons who survived (p = 0.03). Median time from onset of symptoms to beginning of treatment with oseltamivir was 3.0 days for persons who died and for those who survived.The strength of this study was inclusion of nearly all patients with confirmed severe pandemic (H1N1) 2009 in Chile because of timely implementation of a national notification system. The population studied included 97% of hospitalized patients with pandemic (H1N1) 2009.Differences in attack rate (1.2% by reporting of ILI cases and 4% by amount of oseltamivir provided) might be explained by the fact that not all ILI cases were captured (≈20% were lost because of underreporting) by the notification system and oseltamivir was prescribed to persons with illness not included in the ILI case definition. We demonstrated in a pilot study that ≈60%–70% of oseltamivir used complied with the case definition for ILI.>60 years of age did not have a high hospitalization rate (The first wave of pandemic (H1N1) 2009 in Chile showed the highest incidence rate in children 5–14 years of age; persons ≥60 years of age were least affected  2009 because of absence of identified increased risk for infection. Our study indicates an age >60 is the greatest risk factor for a severe outcome during pandemic (H1N1) 2009 and seasonal influenza.Before April 2009, influenza was rarely reported as the cause of death in Chile. Therefore, only CFRs for severe respiratory infection are available for comparison. The CFRs for patients >65 years during winter 2009 was similar to that during previous winters. We conclude that elderly persons’ risk for a severe outcome during pandemic (H1N1) 2009 did not exceed this risk for a severe outcome during seasonal influenza. Previous reports have documented increased risk for severe outcomes in younger persons during pandemic (H1N1) 2009 and the absence of increased risk for disease severity among elderly persons  2009 influenza, similar to that for seasonal influenza. These results can be used for future planning strategies for influenza, strengthening the need for influenza vaccination, opportune medical evaluation, and timely therapy specific for this age group.


Background. Chronic kidney disease is frequently seen in patients with congestive cardiac failure and is an independent risk factor for morbidity and mortality. The aim of this study was to determine the prevalence of chronic kidney disease in patients with hypertension associated congestive cardiac failure. Method. One hundred and fifty patients with hypertension associated congestive cardiac failure were recruited consecutively from the medical outpatient department and the medical wards of the Nnamdi Azikiwe University Teaching Hospital Nnewi over a one year period, January to December 2010. Patients' biodata and medical history were obtained, detailed physical examination done and each patient had a chest X-ray, 12 lead ECG, urinalysis, serum urea and creatinine assay done. Ethical clearance was obtained from the Ethical Review Board of our institution and data analysed using SPSS-version 16. Results. There were 86 males and 64 females with mean age 62.7 ± 12.5 years. The mean blood pressures were systolic 152.8 ± 28.5 mmHg and diastolic 94.3 ± 18 mmHg. 84.7% had blood pressure ≥140/90 mmHg on presentation. The mean GFR was 70.1 ± 31.3 mls/min. 76% of subjects had GFR <90 mls/min and no statistical significant difference between males and females, P = 0.344. The mean serum urea was 7.2 ± 51 mmol/L while the mean serum creatinine was 194 ± 416.2 mmol/L. Conclusions. This study has demonstrated that majority of patients presenting with hypertension associated congestive cardiac failure have some degree of chronic kidney disease. Congestive heart failure (CHF) is common in North America with the prevalence being approximately 2% in adults older than 45 years . While cRenal dysfunction is recognised as an independent risk factor for morbidity and mortality in congestive cardiac failure , 8. The This is a cross-sectional study involving 150 adult patients aged 18–80 years in hypertension associated congested cardiac failure. They were recruited consecutively from medical outpatient clinic and the medical wards of Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, South East Nigeria. A diagnosis of hypertension associated congestive cardiac failure was made using the Framingham criteria  for diagpatient's age between 18 and 80 years;congestive cardiac failure using the Framingham criteria  and the congestive cardiac failure using the Framingham criteria  and the Inclusion criteria for the study wereobvious cause of congestive cardiac failure such as valvular heart disease, cardiomyopathy, and ischemic heart disease;congestive cardiac failure with other comorbidities such as diabetes mellitus, human immunodeficiency virus infection (HIV), chronic obstructive airway disease, infections of the urinary tract, trauma, or taking nonsteroidal anti-inflammatory agents (NSAID), or being involved in strenuous exercise prior to urine production;those found on renal imaging to have preexisting renal disease or suffering from diseases like multiple myeloma, systemic lupus erythematosus (SLE), and so forth.Exclusion criteria for the study wereEthical clearance for the study was obtained from the Ethical Review Board of the Nnamdi Azikiwe University Teaching Hospital Nnewi, Anambra State, South East Nigeria. t-test was used for continuous variables, and χ2 test was used for categorical variables. In the analyses a P value of <0.05 was considered statistically significant. Statistical analysis was carried out using SPSS version 16. Student's There were 86 (57.3%) males and 64 (42.7%) females. The mean age of the subjects was 62.7 ± 12.6. The majority (56.7%) were traders. The educational attainment of the subjects is shown in 127 (84.7%) of the patients were aware that they had hypertension. The mean systolic blood pressure was 152.8 ± 28.5 mmHg while the mean diastolic blood pressure was 94.3 ± 18 mmHg. The mean duration of hypertension was 7.6 ± 8.9 years. 37 (27.3%) of the subjects had blood pressure less than 140/90 mmHg on presentation.P = 0.344, 0.159, and 0.100, resp.). The mean GFR of the study population was 70.1 ± 31.3 mLs/min. 114 (76%) of the subjects had renal impairment (GFR < 90 mLs/min). Mean serum urea concentration was 7.2 ± 5.1 mmol/L while mean serum creatinine was 194 ± 416.2 mmol/L. Proteinuria was found in 52 (34.6%) of the subjects. Our study found impaired renal function in 76% of the subjects which confirms the assertion that chronic kidney disease is common in patients with congestive cardiac failure. The majority of subjects (43.3%) had mild chronic kidney disease . This compares favorably with the findings of 72% prevalence in Blacks and 69% in Whites found by Smith et al. . The 76% Obasohan and Ajuyah  in the NThe high values may also reflect the relatively lesser contribution of coronary artery disease to heart failure in Black hypertensive patients than Caucasian patients . Chronic kidney disease in congestive cardiac failure patients has become increasingly recognized as an independent risk factor for morbidity and mortality . HyperteIn view of the high prevalence of chronic kidney disease in hypertension associated congestive cardiac failure it is recommended that health awareness campaigns targeted at vulnerable groups be initiated, for the detection of chronic kidney disease in those with congestive cardiac failure and hypertension using the media (radio and television), health talks at town/village meetings, churches, and so forth.Also clinicians who provide care should be encouraged to screen hypertensive patients and those in congestive cardiac failure periodically by estimating the GFR to detect a decline in renal function and measures instituted to reduce the morbidity and mortality associated with chronic kidney disease in congestive cardiac failure.This study showed that there is a high prevalence of chronic kidney disease in patients in congestive cardiac failure and is in agreement with similar studies done in other countries. There are differences in the prevalence of chronic kidney disease in congestive cardiac failure in different studies done due to nonuniformity in the criteria for defining chronic kidney disease.


This study aims to estimate the toxicological risk of PM2.5 from biomass burning in children and adolescents between the age of 6 and 14 in Tangará da Serra, a municipality of Subequatorial Brazilian Amazon.Exposure to fine fractions of particulate matter .Risk assessment methodology was applied to estimate the risk quotient in two scenarios of exposure according to local seasonality. The potential dose of PM2.5 was 1.95 μg/kg.day (95% CI: 1.62 – 2.27) during the dry scenario and 0.32 μg/kg.day (95% CI: 0.29 – 0.34) in the rainy scenario. During the dry season, children and adolescents showed a toxicological risk to PM2.5 of 2.07 μg/kg.day (95% CI: 1.85 – 2 .30).Male asthmatic children under the age of 8 at normal body rate had the highest risk quotient among the subgroups. The general potential average dose of PM2.5 resulting in toxicological risk for this multi-pollutant. The toxicological risk quotients of children in this region were comparable or higher to children living in metropolitan regions with PM2.5 air pollution above the recommended limits to human health.Children and adolescents living in the Subequatorial Brazilian Amazon region were exposed to high levels of PM With coe health  of thosee health ,30.2.5 in the Amazon region. It furthermore provides a basis for comparison between other studies using the same methodology across emission sources, age and region.Risk Assessment Methodology was sensitive in accommodating characteristics in specific groups and producing estimates of risk for respiratory adverse health effects. It identified specifically children younger than 8 as having more vulnerability to high levels of PMPM, Particulate matter; BMI, Body mass index; PHAs, Polycyclic aromatic hydrocarbon; CI, Confidence interval; SD, Standard deviation.The authors declare they have no competing interests.2.5 Risk Assessment methodology; WLJ and BFAO the statistical and sensitivity analysis; PA contributed with the air pollution and meteorological data. PHNS provided the data of the panel study. All authors contributed to revising the final manuscript. All authors read and approved the final manuscript.BFAO, EI and SH designed and implemented the PM


The objective was to assess correlation between organ failure and outcomes in patients admitted with neutropenic sepsis to an adult ICU in a district general hospital.Retrospective data were collected for admissions with neutropenic sepsis to the ICU over a 3-year period. The Ward Watcher electronic system was used to collect data on the level of organ support on the ICU. Outcomes assessed were 30-day and 1-year mortality.9/l and 52% had zero count during their ICU stay. A total of 41.3% had positive blood cultures. Mortality with negative blood cultures was 73%. Overall 30-day mortality was 58.6% and 1-year mortality was 79.3%. Ventilator support was needed in 83% with a mortality of 88%. Inotropes were required in 48.2% and there was a 71% 30-day mortality. Renal support was commenced in 27.5% with 100% mortality. The 30-day mortality was 100% in patients requiring invasive ventilation and renal support. Mortality was also 100% in those requiring three-organ support (Figure Twenty-nine neutropenic patients were admitted during the study period; 93% had haematological malignancy while 7% showed no evidence of malignancy. The mean neutrophil count was 0.2 × 10Our data suggest a significant mortality in mechanically ventilated patients with neutropenic sepsis. This rises to 100% if two or more organs are supported, especially if one of them is the kidney. Early recognition and intervention to prevent progression to multiorgan failure is paramount to improve outcomes.


This cycle was repeated for ∼6 weeks. The 5 patients received a total of 19 cycles of treatment with decitabine. No patient achieved complete or partial remission. An antileukemic effect was observed in 25% of courses (3/12). An increase in platelet count of >20×109/l was observed in 26.3% (5/19) of cycles compared with previous treatment. An increase in hemoglobin concentration of >20 g/l was observed in 36.8% (7/19) of cycles in comparison to previous treatment, four of which achieved normal hemoglobin levels. One patient became red blood cell transfusion-independent. The median survival time was 19.8±4.8 months. Survival time from decitabine administration to mortality was 13.2±5.1 months. The main side-effect was bone marrow suppression with grade III–IV thrombocytopenia, grade III–IV leukocytopenia, grade III–IV neutropenia and anemia accounting for 94.7% (18/19), 47.4% (9/19), 89.5% (17/19) and 21.1% (4/19), respectively. Severe infection or bleeding was not observed and no patient stopped treatment due to adverse effects. In conclusion, extremely low-dose decitabine may be used safely in elderly patients and achieved longer survival times than reported previously in AML patients aged 80 and above. It is suggested that complete remission may not be the primary objective, while improvement of quality of life may be a better choice in AML patients over 80 years old. The cases observed in our study were limited, so more cases are required for further study.The incidence of acute myelogenous leukemia (AML) in patients over 80 years old is >20 times greater than that observed in younger patients. Previously, no standard treatment protocol for elderly patients with AML existed, however the development of hypomethylating agents, including decitabine, has brought about promising results in AML. In the present study, we report on the usage of a lower than routine dosage of decitabine in patients over 80 years old with AML. Since January 2010, 5 patients diagnosed with AML over the age of 80 years old received treatment with decitabine in our hospital. Decitabine was administered at a dose of 10–15 mg/m The incidence of acute myelogenous leukemia (AML) in the elderly population is increasing due to the aging of the general population. Statistics from U.S. National Cancer Institute demonstrated that the incidence of AML is 23/100,000 in the age range of 80–84 years, while 21.2/100,000 over the age of 85, which is ∼20 times greater than the incidence in younger patients ; iv) oftet al reported that low-dose decitabine was effective in myelodysplastic syndrome (MDS) and this finding was confirmed in further clinical trials , as well as normalizing terminal differentiation, the aging process or apoptosis of cells. In 1992, Zagonel l trials . Subsequl trials ,22. In pl trials . TherefoFive elderly patients aged over 80 years old with AML were enrolled in January 2010 and treated with decitabine in the Department of Geriatric Hematology in the People’s Liberation Army General Hospital . The study was approved by the Ethics Committee of The Chinese PLA General Hospital, Beijing, China. Written informed consent was obtained from the patients priort to the study.2 by continuous intravenous infusion over 1 h and repeated every other day for a total of 5 days. Each cycle was repeated every 6 weeks. No other chemotherapy was provided from administration of decitabine to mortality. Hematopoietic colony-stimulating factors were used during bone marrow suppression. Supportive care measures included the use of red blood cell transfusion in patients with a hemoglobin level <8 g/dl and platelet transfusion in patients with a platelet count <20×109/l or where active bleeding existed.Decitabine  was administered at a dose of 10–15 mg/mBlood routine, liver and kidney function tests, chest X-ray, echocardiography, cardiac enzymes and electrocardiograms were performed prior to and following treatment. Bone marrow examination was performed following some cycles of treatment.9/l, white blood cell (WBC) levels of >1.5×109/l and absence of extramedullary infiltration. ii) Partial remission (PR): either blast cell levels in the bone marrow between 5–25%, platelet levels of >100×109/l and WBC levels of >1.5×109/l or blast cell levels in the bone marrow of <5% but platelet levels of <100×109/L and WBC levels of <1.5×109/l. iii) Antileukemic effect (ALE): blast cells in the bone marrow reduced by >25% compared with before treatment, but do not meet PR criteria. iv) Progressive disease (PD): blast cells in the peripheral blood or bone marrow increase >25% compared with before treatment. v) Stable disease (SD): other than CR, PR, ALE and PD.Treatment efficacy was evaluated according to the following: i) complete remission (CR): blast cell levels in the bone marrow of <5%, platelet levels of >100×10The side-effects of chemotherapy were graded according to WHO criteria: grade 0, grade I, grade II, grade III and grade IV.Numerical data are reported as mean ± standard deviation and were analyzed with the Student’s t-test (pair-wise comparison for pre- and post-treatment comparison). Event rate was analyzed using the Chi-square test. P<0.05 was considered to indicate a statistically significant result.The clinical information of the 5 patients is presented in 9/l was observed in 26.3% (5/19) of cycles compared with previous treatment. The mean time to achieve platelet best response was 35.6 days. An increase in hemoglobin concentration of >20 g/l was observed in 36.8% (7/19) of cycles in comparison to previous treatment, four of which achieved normal hemoglobin levels. The mean time to best hemoglobin response was 35.4 days. One patient became red blood cell transfusion-independent.Bone marrow examination was performed following 12 cycles of treatment. No patients achieved CR or PR. ALE was observed in 25% of courses (3/12). An increase in platelet count of >20×10Median survival time was 19.8±4.8 months , which wThe main side-effect was bone marrow suppression. The lowest value and days to the lowest value of blood routine tests are presented in in vitro. Reversal of aberrant methylation leads to re-expression of silenced tumor suppressor genes. In 2006, the US FDA approved decitabine for the indication of MDS. The efficacy of low-dose decitabine in the treatment for MDS laid the foundation for AML treatment research. Decitabine to treat AML has been evaluated in a number of clinical trials, however these only included a few patients aged 80 years and above.Abnormalities in DNA methylation play an important role in the development of hematological malignancy. Decitabine, a hypomethalyting agent, reverses hypermethylation of genes Elderly patients with AML cannot tolerate either hematopoietic stem cell transplantation or standard intensity chemotherapy. Therefore, regimens with a lesser degree of side-effects are recommended. Furthermore, there is no standard treatment regimen for elderly AML patients. Treatment should be individualized based on the nature of the disease, the physiological status of the patient and the patient’s preferences. We consider that CR may not be the primary objective, while improvement of life quality may be a better choice . AccordiThe main adverse effect of decitabine in elderly patients was bone marrow suppression, most notably in thrombocytopenia and neutrocytopenia. This often occurred 2 weeks following treatment. No severe bleeding or infection was observed following reinforcement of supportive care. If strong supportive care is provided, administration of decitabine in elderly patients is relatively safe.The cases observed in our study were limited, hence a comprehensive conclusion cannot be made. More cases are required for further study to confirm the results.


Background. We analyzed radical TUR-PCa against localized prostate cancer. Patients and Methods. Seventy-nine out of 209 patients with prostate cancer in one lobe were studied. Patients' age ranged from 58 to 91 years and preoperative PSA, 0.70 to 17.30 ng/mL. In other 16 additional patients we performed focal TUR-PCa. Patients' age ranged from 51 to 87 years and preoperative PSA, 1.51 to 25.74 ng/mL. Results. PSA failure in radical TUR-PCa was 5.1% during the mean follow-up period of 58.9 months. The actuarial biochemical non-recurrence rate was 98.2% for pT2a and 90.5% for pT2b. Bladder neck contracture occurred in 28 patients (35.4%). In 209 patients, pathological study revealed prostate cancer of the peripheral zone near the neurovascular bundle bilaterally in 25%, unilaterally in 39% and no cancer bilaterally in 35%, suggesting the possibility of focal TUR-PCa. Postoperative PSA of 16 patients treated by focal TUR-PCa was stable between 0.007 and 0.406 ng/mL at 24.2 months' follow-up. No patients suffered from urinary incontinence. Bladder neck contracture developed in only 1 patient and all 5 patients underwent nerve-preserving TUR-PCa did not show erectile dysfunction. Conclusion. Focal TUR-PCa was considered to be a promising option among focal therapies against localized prostate cancer. Cryotherapy , 12 and  We previously reported that radical transurethral resection of prostate cancer (RTUR-PCa) could be a radical therapy against localized prostate cancer . We thenBetween December 2003 and July 2009, a total of 261 RTUR-PCa were performed under spinal anesthesia in 209 patients with localized prostate cancer. Clinical stages were determined according to the UICC TNM staging system of 1997. We performed bone scintigraphy and computerized tomography for the purpose of metastatic workup in patients who had initial PSA levels of 20 ng/mL or more. And we recommended the patients who had PSA level between 10 and 20 ng/mL and higher Gleason score to undertake such examinations with some of them having refused to take. We informed the patients that the procedure was not a standard radical surgery, and those who refused this procedure were excluded from the study. We also excluded patients who might not tolerate standard transurethral resection of the prostate (TURP). Patients who gave the written informed consent were eligible for the study in the order they were given a diagnosis of localized prostate cancer. Institutional review board approved the TUR-PCa program after a preliminary study. We thought that the most appropriate indication of focal therapy should be localized prostate cancer in one lobe. We reviewed RTUR-PCa cases to find patients to match such criteria. Seventy-nine of the above 209 RTUR-PCa patients diagnosed to have prostate cancer in one side of the lobes were included in the present study. In 74 out of these 79 patients, cancer was detected by ultrasound-guided transrectal needle biopsy, and in the other 5 patients prostate cancer was incidentally detected after TURP for benign prostate hyperplasia (BPH). We obtained a total of 14 biopsy samples per case from the peripheral and transition zone including far lateral part, dividing the prostate into base (2 cores), upper middle part (2 cores), lower middle part (6 cores), and apex (4 cores), and we marked at the dorsal end to obtain tumor maps. In the patients underwent TURP; after resecting most of the transition and central zone, we made a slightly deeper resection dividing the residual thin transition zone and peripheral zone into 6 parts and collected the resected specimens separately to identify the affected sites by pathological examination (advanced TURP) . We performed 93 RTUR-PCa in 79 patients under spinal anesthesia. Patients ranged from 58 to 91 years old  and preoperative PSA, 0.70 to 17.30 ng/mL . Chlormadinone acetate was administered for a mean period of 4.6 months in 52 patients. Between July 2007 and September 2011, we performed FTUR-PCa in 16 patients. FTUR-PCa includes two different procedures: in one procedure we radically resect the affected one lobe with unaffected lobe being resected as advanced TURP for BPH , and in the other procedure we radically resect both lobes except for the prostate tissues near the neurovascular bundle  based on the tumor mapping. Patients ranged from 51 to 87 years old  and preoperative PSA, 1.51 to 25.74 ng/mL . Chlormadinone acetate was not administered in this group.2O and an irrigation rate of 250 mL/min using D-sorbitol solution. After resecting almost all the transition and central zone, we tried to resect and fulgurate the peripheral zone completely especially where cancer was detected by biopsy. The resection was performed as deep as adipose tissue was identified and as distal as the external sphincter was identified. But we did not resect prostate tissues until adipose tissue was exposed all around the operative field. We aggressively fulgurated the area adjacent to where adipose tissue was exposed because the remaining prostate tissue could be considered a thin layer. We especially paid attention not to distend the bladder too much to prevent a high irrigation pressure and resultant TUR syndrome. Special attention was also paid to avoid injury to Santorini's plexus and the rectum. The procedure was started from the 12 o'clock position, dividing the prostate into 6 parts, and resected specimens were separately collected from each part to examine the distribution of cancer. The seminal vesicle was partially resected at its attached part to the prostate between the 4 and 8 o'clock positions to determine the invasion of cancer. Finally the verumontanum was resected to achieve the complete resection of prostate tissue. A bag catheter was removed on the third postoperative day. One urologic surgeon (M. Morita) performed all operations. We used a standard TURP setup with an irrigation pressure of 80 cm H Postoperative PSA was measured every two months starting two months after the operation. PSA failure was suspected when PSA levels showed a consecutive rise over 0.2 ng/mL. But when the PSA level reached a plateau between 0.2 and 1.0 ng/mL, we did not immediately think that the patients were in a treatment failure. This was also applied to the indication of the second RTUR-PCa. We evaluated stress urinary incontinence by asking patients the postoperative status of urinary leak on a cough or a sneeze and needs for urinary pads.The mean follow-up period of 79 patients was 58.9 ± 17.0 months . The operation time ranged between 65 and 120 minutes , and the resected tissue weight was between 5.0 and 37.0 grams . The preoperative PSA value was 5.77 ± 3.51 ng/mL . Clinical stages were as follows: T1b, 28 cases; T1c, 47; T2, 4; and pathological stages: pT2a, 56 cases; pT2b, 21; pT3, 2 . GleasonOne patient died of cerebrovascular accident 15 months postoperatively with a low PSA value of 0.012 ng/mL. No patients died of prostate cancer. Sixty-four patients had stable PSA after the first operation. The second operation was required in 14 patients after a mean period of 16.4 months  due to rising PSA levels. Resected tissue weight was between 5.0 and 12.0 grams . No cancer was detected by pathological examination in 3 patients. The second operation was required in 10 (40.0%) out of 25 patients before April 2006 but in only 4 (7.0%) out of 54 patients after that time, suggesting that there seemed to be a learning curve for the operative technique. At the final followup, there were 75 (94.9%) patients with stable PSA levels: PSA ≦ 0.01, 40 cases; ≦0.02, 12; ≦0.03, 5; ≦0.04, 5; ≦0.1, 5; ≦1.0, 8. PSA failure developed in 4 (5.1%) of the studied patients. Clinical stages were as follows: T1b, 1 case; T1c, 2; T2, 1; pathological stages: pT2a, 1 case; pT2b, 2; pT3, 1. In all cases studied, the actuarial biological non-recurrence rate was 96.4% for the clinical stage T1b and 95.7% for T1c at 58.9 months . PSA faiTo evaluate the distribution of prostate cancer near the neurovascular bundle, we studied the result of pathological examination of resected samples in 209 RTUR-PCa patients. Cancer was detected at the 4 to 6 o'clock position in 44 patients (21%), at the 6 to 8 o'clock position in 38 patients (18%), bilaterally (at the 4 to 8 o'clock position) in 74 patients (35%) and was not detected bilaterally in 53 patients (25%). Concerning the 16 patients underwent FTUR-PCa, the follow-up period ranged from 3 to 53 months , operation time 80 to 120 minutes , and resected tissue weight 12 to 30 grams . Postoperative PSA was stabilized between 0.07 and 0.406 ng/mL . The Gleason scores were as follows: 5, 1 case; 6, 4; 7, 8; 8, 1; 9, 2. Clinical stages were T1c in all patients, and pathological stages were as follows: pT2a, 10 cases and pT2b, 6. There were 11 cases underwent one lobe radical TUR and 5 cases underwent nerve sparing radical TUR. Eight (72.7%) out of 11 patients underwent one lobe radical TUR had the postoperative pathological stage of pT2a. TUR syndrome  and perioperative bleeding (bleeding during the procedure or bladder tamponade that requires blood transfusion) did not develope.As for the postoperative complication of RTUR-PCa, urinary incontinence was seen in about half of the patients when a bag catheter was removed on the third postoperative day. Incontinence soon improved until the third postoperative week, and no patients complained of stress urinary incontinence at all after the third postoperative month. Bladder neck contracture developed in 28 patients  mostly three to four months postoperatively. Other complications included one pubic osteitis  and one acute epididymitis . Erectile function was preserved after the operation in 9 (50.0%) of the evaluated 18 sexually active patients. In FTUR-PCa, bladder neck contracture developed in only 1 out of 16 patients. We experienced no stress urinary incontinence, and erectile function was preserved in the all 5 patients underwent nerve-sparing TUR. Out of 79 patients with the clinical stage of T2a, 56 (70.9%) patients were finally diagnosed to have the pathological stage of pT2a disease with PSA non-recurrence rate of 98.2% at a mean follow-up period of 58.9 months. These results may support that FTUR-PCa is a promising procedure. But it may be desirable to make the cancer distribution in the prostate more accurate to select proper candidates of the procedure. Only 27.3% to 35.1% of patients with unilateral cancer on biopsy are reported to have cancer in one lobe on radical prostatectomy samples , 19. Cra The number of patients with low-volume, low-grade localized prostate cancer has increased after the introduction of PSA into health check-up program , 22. Abl It is still controversial to support or not a mass screening of prostate cancer because screening may lead to overdiagnosis and overtreatment. Active surveillance policy or watchful waiting, which is an ultimate noninvasive procedure, is then accepted to care for the patients with low-risk cancer , 29. But Dissemination of cancer cells may occur during TUR, but the effect on the clinical outcome is controversial –32. Our  Extravasation of irrigation fluid is sure to occur during the operation, but there were no patients in whom water intoxication developed with the lowest irrigation pressure, and postoperative serum electrolytes were kept normal. At present much safer operation is possible with the use of a bipolar TUR system. The most frequent postoperative complication was bladder neck contracture occurred in 35.4% of patients 3 to 4 months after surgery. This had been anticipated because of aggressive bladder neck resection to achieve radicality. It was easily treated by optical urethrotomy under caudal block on a day-surgery basis. In FTUR-PCa, occurrence of bladder neck contracture is expected to be low because it is a radical procedure in only one affected lobe with advanced TUR in the other lobe. The effect of chlormadinone acetate on postoperative PSA must be considered in the present study. We could not find any reports that describe the duration of the suppressive effect of chlormadinone acetate in patients with prostate cancer. But in patients with prostate hyperplasia 50 mg/day of chlormadinone acetate given for 16 weeks, PSA levels are reported to return to the baseline levels 32 weeks after discontinuation . In the We could get a satisfactory cancer control with less invasive procedure of RTUR-PCa and FTUR-PCa. Although the results of long-term followup with more cases need to be studied, the procedure we report here could be a potential option of focal therapy against localized prostate cancer with minimum adverse effect on urinary continence and erectile function.


The OTA content of 30 roasted coffees purchased in French supermarkets was evaluated by two validated different methods: one using immunoaffinity column (IAC) clean-up after alkaline extraction; the second using toluene extraction under acidic conditions. OTA recoveries (0.5 to 5 µg/kg) ranged from 16–49% with the alkaline extraction method and 55–60% with the acidic method. OTA recoveries from prepared beverages were similar with all methods (75–80%). All samples containing OTA ranged from trace (<LOQ) to 11.9 µg/kg. About 20 to 140% of OTA passed through the beverages. Recoveries of over 100% of OTA in beverages were due to three types of interferences: (i) formation of open-ring OTA (OP-OA) during alkaline extraction, (ii) isomerization of OTA during roasting, and (iii) presence of the nonchlorinated analogue OTB. The first two types of interference generate OTA derivatives that are not recognized by OTA antibodies, while OTB cross-reacts with OTA-antibodies. These analytical problems will seriously impact the amount of OTA detected, especially at the levels close to the limits from the EU legislation. Underestimation of OTA could be highly dangerous for health.  Penicillia in cereal or Aspergillii in wine and coffee [Ochratoxin A (OTA) is a secondary metabolite produced either by d coffee ,2. OTA id coffee ,4. Simild coffee ,6,7 may d coffee ,11,12,13d coffee ,16,17,18d coffee , isomerid coffee  and therd coffee ,19,20,21d coffee . et al. [Therefore, it is essential to use reliable and sensitive analytical methods for the detection of OTA in individual foodstuff. There are numerous methods for the determination of OTA in foodstuffs, such as thin layer chromatography, enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC) and liquid chromatography-mass spectroscopy (LC-MS) . The anaet al.  in whichet al. 1996 [All reagents  were of normapur grade. All solvents  were of HPLC grade from ICS (France). Deionized water was used for the preparation of all aqueous solutions and for HPLC. OTA and OTB standards, free from benzene and carboxypeptidase were from Sigma Chemicals (France). The immunoaffinity columns (IAC) (Ochraprep®) were from Rhone Diagnostic technologies (France). OP-OTA was prepared as described by Xiao al. 1996 . In brieThirty ground roasted coffee samples were purchased in French supermarkets. OTA was extracted by three methods: two using IAC cleanup ,27 and t2 0.4 M and 100 mL Toluene. The mixture was continuously shaken for 60 min. After separation, 50 mL of toluene phase containing OTA was purified on SEP pack. The column was washed twice with 10 mL n-hexane, twice with 10 mL acetone/toluene , and once with 5 mL toluene. OTA was recovered by addition of 15 mL toluene/acetic acid  two times. 30 mL of 5% natrium bicarbonate solution was added twice. The mixture was shaken for 10 min. After separation, OTA was present in the aqueous phase. The solution was acidified by the addition of concentrated HCl until pH 2 was reached. Finally, 60 mL of CHCl3 was added and the mixture was shaken for 10 min. After separation, the chloroformic phase was recovered. This step was performed twice. Chloroform containing OTA was evaporated to dryness. OTA was dissolved in methanol (500 µL). Twenty grams of ground coffee were mixed with 30 mL HCl 2 M; 50 mL MgCl2HPO4), 0.2 g kalium dihydrogenophosphate (KH2PO4), 0.2 g KCl, and 900 mL water) were added to 10 mL of extract. This mixture was purified on an Ochrastar Immuno Affinity Column (IAC). The column was washed twice with 10 mL PBS. OTA was recovered by elution of 1.5 mL of methanol, evaporated to dryness and dissolved again in 500 µL methanol.Ten grams of ground coffee were mixed with 100 mL of solution containing methanol/natrium bicarbonate 3%, 50/50 (v/v) and shaken for 30 min. The solution was filtered through Whatman paper No. 4. Twenty milliliters of this extract were diluted with 20 mL of natrium bicarbonate 3% and purified on a phenyl silane column. The column was washed with 10 mL methanol/natrium bicarbonate 3%,  and 5 mL of natrium bicarbonate 1%. OTA was recovered by addition of 10 mL methanol/water . 30 mL of phosphate buffer solution (PBS)  and shaken for 10 min. The solution was filtered through Whatman paper No. 4. Four milliliters of this extract were mixed with 100 mL PBS. This mixture was purified on an IAC. The column was washed two times with 10 mL ultra pure water. OTA was recovered by elution in 4 mL of methanol, evaporated to dryness and dissolved again in 500 µL methanol.2HPO4), 0.6 kalium dihydrogenophosphate (KH2PO4), 0.6 g KCl, 900 mL water adjusted to pH 7.4 and loaded on the IAC. A second purification was made according the Pittet’s method [OTA was also analyzed in coffee beverages that were made using two different kinds of machines (filtration technique and piston) . Using ts method . In thisOTA has also been extracted with cold water. Thirty grams of coffee were placed in the presence of cold water for 24 h. In each case, the beverage (20 mL) was used as extract and diluted with 80 mL of PBS then passed through the IAC.2) with inner porosity of 3 µm, with an ultrasep C18 10 µm precolumn, 1 cm long from ICS, under isocratic condition (mobile phase: orthophosphoric acid at 0.33 M/ACN/propan-2-ol (600:400:55), flow rate 0.8 mL/min). HPLC analysis used a Gilson 811B dynamic chromatography pump coupled to a Spectra Physics 2000 ﬂuorescence spectrophotometer and an ICS autosampler. Detection was performed with a programmable Merck HITACHI FL Detector L-7485 . The chromatograms were analyzed by Normasoft software provided by ICS (France).OTA was analyzed by HPLC using C18 column PRONTOSIL 120 . They were used to calibrate the LC detector response. The concentration of the OTA stock solutions was determined by measuring the UV absorbance at 333 nm with a molar extinction coeﬃcient ε of 5500 moltraction , alkalintraction , and Pittraction .2) was 0.997. The limit of detection (LOD) was 0.025 µg/kg and the limit of quantification (LOQ) was 0.04 µg/kg at nine times background.The coeﬃcient of linearity (ROTA recoveries: Three coffee samples spiked with 5 µg/kg (corresponding to EU legislation), were extracted by the three methods and were analyzed on the same day, by the same operator and with the same HPLC system. The average recoveries were 45 ± 4% for Entwisle method ; 71 ± 1%2O) was added and the mixture was incubated at room temperature overnight. The sample was analyzed under the same HPLC chromatographic conditions as used above. The OTA peak disappeared whereas the peak of α-OT appeared. The OTB peak disappeared whereas the peak of β-OT appeared. The confirmation of the presence of OTA (or OTA derivatives) in coffee samples was achieved by the following technique: an aliquot, taken from the purified extract of a sample where OTA was detected by the HPLC analysis, was dried. The pellet was dissolved in 975 µL of a buffer solution of 0.04 M Tris-HCl, 1 M NaCl, pH 7.5. Then, 25 µL of carboxypeptidase  was spiked with increasing amounts of OTA . The recovery limits commonly accepted for a level of contamination of OTA around 10 µg/kg are 70–125% . For thiThe major difference between the two IAC methods was the relative proportion of PBS added to the extract and the duration of shaking incubation. The conditions in Pittet’s method  bring thThirty samples were analyzed by both official methods . Ten samIn all samples, trace amounts of OTA (<LOD) could be detected. The amount of OTA, whatever the method of extraction, ranged from trace (<LOD) to 11.9 µg/kg. For 27% of the samples, the OTA amount ranged between LOD and 0.5 µg/kg, 33% samples contained OTA between 0.5 and 1 µg/kg, while 37% samples contained OTA between 1 and 3 µg/kg. Only one sample (3%) contained OTA above the EU limit of 5 µg/kg  and reacet al. [et al. [For six samples out of 10 analyzed, the amount found by Pittet’s method  was signet al.  correspo [et al.  correspoIn 9 samples , OTB (dechlorinated OTA) was detected, but not quantified. OTB could lead to underestimation of OTA (see paragraph 3.3).et al. (2004) [et al. (2007) [Our results are in good agreement with the findings of others. For example, reported amounts of OTA in coffee have been from 0.5 to 23.0 ng/g , 9.9 to . (2004)  analyzed. (2007) , a total. (2007) .Post-harvest practices, particularly drying, affect OTA contamination . The higTo analyze the amount of OTA passing through the beverage, only clean-up on IAC without extraction was performed. Coffee beverage is prepared by passing hot water over ground coffee beans and is equal to the crude extract. The recovery of OTA was evaluated on coffee spiked with increasing amounts of OTA before infusion, or by addition of OTA to the crude extract. In this analysis the % recovery of OTA was fairly constant , becauseThe most contaminated roasted coffees were used to prepare coffee beverage. Nineteen samples were used to prepare beverages using two different techniques: the filtration technique (infusion) or piston technique (decoction). The percentage of OTA passing through the beverage was calculated using the value obtained by the EN 14132 method  as 100% The amounts of OTA passing through the beverage are slightly higher (ranging from 5–20%) when the coffee is made by the electric machine (infusion) compared to piston machine (decoction).The percentage of OTA found in the beverages varied from 13–141% of the initial amount of OTA found in ground coffee . Several authors described also that OTA present in roasted coffee essentially passes completely into the brew (or found even more OTA), whereas some others did not find any passage ,16,36,43Percentage of OTA passage over 100% confirms the presence of masked OTA, probably isomerization of OTA by roasting ,43 and iAs in the case of breakfast cereal ,33, someFormation of OP-OA by alkalinization leads to the underestimation of OTA. This loss is partially counteracted in the Pittet’s method because the large dilution of the extract lowers the pH, allowing reconversion of OP-OA into OTA . Interference is also due to the presence of OTB, which was detected in the most OTA contaminated coffee.For this reason, we tested the cross reactivity of OTA, OTB and OP-OTA with the antibodies from the IAC used. When 50 ng of each toxin is spiked on a coffee extract before IAC, the recoveries of OTA and OTB were respectively of 57% and 81%, whereas OP-OTA is not recognized (amount detected is below the LOQ). The respective recoveries when each derivative is spiked independently were 80% for OTA, 91% for OTB and 0% for OP-OTA. This indicates that: (1) OTB is recognized by the antibodies of the OTA IAC; (2) the affinity of OTB is higher than that of OTA on these columns; (3) OP-OTA is not recognized by OTA-IAC. This explains the data obtained with the most contaminated coffee sample, for which much higher OTA amounts are found in acidic conditions without IAC (15 µg/kg) than by the two other methods (9.5 µg/kg). Thus, the loss of OTA by the two methods—including IAC cleanup—is due to the transformation of OTA into OP-OTA and the presence of OTB, which has a higher affinity and contribute to saturation of column. Our data show that OTA in coffee is generally underestimated due to OTB and other substances also present in coffee that interfere with the OTA antibodies. In addition, extractions in alkaline medium lead to conversion of OTA into open-ring OTA (OP-OA), which is not recognized by OTA antibodies. In general, the amount of OTA found in ground coffee was below the limit of residue enforced by EU . Neverth


Within the lymphocyte population the proportion of B cells increased from 4 to 46% over the 5 week exposure period. Mice developed perivascular, peribronchiolar and alveolar inflammation which increased in severity during the five week exposure period. The inflammation was accompanied by epithelial and mucus cell hypertrophy/hyperplasia in the bronchi and bronchioles which reached maximum severity during Weeks 3 to 5. Perivascular/peribronchiolar fibrosis peaked in Week 5. Therapeutic treatment with prednisolone and roflumilast significantly (P<0.001) inhibited BALF cell recruitment and reduced the severity of the airway remodelling suggesting this model, in our laboratory, has the potential to test novel compounds for the treatment of allergic disorders.House dust mite (HDM) allergens are associated with allergic disorders and the use of this clinically relevant allergen is increasing in animal models. We assessed the chronic inflammatory time course and the anti-inflammatory efficacy of a phosphodiesterase 4 inhibitor and a corticosteroid. BALB/c mice were challenged intranasally with HDM for 5 days/week for 5 weeks. Animals were sacrificed weekly 24 hours after final challenge and recruitment of inflammatory cells assessed in bronchoalveolar lavage fluid (BALF). Lung tissue was stained for the evaluation of a histopathological response. Roflumilast (10 mg/kg) and prednisolone (10 mg/kg) were administered orally twice daily from Week 3. Chronic HDM extract exposure resulted in significant recruitment of eosinophils, neutrophils, lymphocytes and macrophages as early as Week 1, peaking (1.13±032, 0.31±0.05, 0.66±0.10 and 0.33±0.04 x10


To the Editor: Norovirus (NoV) has been identified as one of the major causal agents of nonbacterial, acute gastroenteritis in humans  suggest that this increase is related to the emergence of a new GII.4 variant, termed Sydney_2012 .During July 2011–December 2012, fecal specimens from 748 outpatients (≥16 years of age) with acute gastroenteritis who visited 1 of the 2 sentinel hospitals in Shanghai were collected and stored at Shanghai Public Health Clinical Center at −70°C. Molecular detection of GI and GII NoV was performed by using conventional reverse transcription PCR as described . The prevalence of GII NoV during the same period in 2011 was low; the detection rate was 6.90% (8 cases in 116 outpatients). Genotyping analysis of the strains detected in these 3 months in 2012 (39 strains were sequenced) showed that except for 1 GII.6 strain and 3 GII.4 2006b strains, the other 35 strains sequenced all belong to the new established cluster of GII.4, termed Sydney_2012. Retrospective analysis indicated that the novel GII.4 variant had already been detected in 2 outpatients during September 2011 in Shanghai.http://blast.ncbi.nlm.nih.gov/Blast.cgi) searches, the most closely related NoVs (98%–100% nucleotide identity) were 4 GII.4 viruses recently detected in Australia and Hong Kong. The new GII.4 strains detected in Shanghai also clustered with these strains, a finding that was supported by bootstrap values >70% . The 3′ end of RNA-dependent RNA polymerase gene sequences also confirmed that the new GII.4 strains were recombinants, with a GII.e polymerase and GII.4 capsid , and most epidemics have been associated with emergence of a novel GII.4 cluster (


Data on inpatient admissions for COPD and ambient on air pollution levels in Taipei were obtained for years 2006 to 2010. We estimated the relative risk of inpatient admissions for COPD using a case-crossover design with the following control variables: weather measures, day of the week, seasonality, and long-term time trends. For the single-pollutant model (not controlling for other atmospheric pollutants), COPD admissions were significantly and positively associated with higher PM2.5 levels during both warm days (>23 °C) and cool days (<23 °C), with an interquartile range increase of 12% (95% CI = 8–16%) and 3% (95% CI = 0–7%) in COPD admissions, respectively. In the two-pollutant models, PM2.5 remained significant even controlling for SO2 or O3 on both warm and cool days. Taken as a whole, our study demonstrates that higher levels of PM2.5 may increase the risk of inpatient admissions for COPD.We undertook this study to investigate whether there is an association between atmospheric fine particles (PM It i2.5 due to lack of PM2.5 monitoring data [2.5 and hospital admissions (or ER visits) for chronic obstructive pulmonary disease (COPD) [Relatively few epidemiologic studies have been undertaken which specifically address the health effects of PMing data . Consideing data ,23,24,25ing data . Severale (COPD) ,28,29,3010 levels [2.5 levels, due primarily to the lack of monitoring data [There is a substantial number of epidemiological studies in Taiwan reporting associations between mortality/morbidity with ambient PM0 levels ,34,35,36ing data ,39,40,412.5 levels on daily inpatient admissions for COPD among residents of Taipei, the largest city in Taiwan, using over 5 years of observations from 2006–2010, and a case-crossover design.Our primary objective was to examine the short-term impact of PM2.5 levels in Taipei for the 5-year period from 2006 through 2010. Taipei is the largest metropolitan city in Taiwan with a population of approximately 2.64 million located in northern Taiwan. The major air pollution source is automobile exhaust emission. Taipei has a subtropical climate, with an annual average temperature of 23 °C. (the months with a mean temperature below 23 °C are from November to April and May to October are the months with a mean temperature above 23 °C).This study examined daily variations in hospital admissions for COPD in relation to PMThe National Health Insurance (NHI) Program, which provides compulsory universal health insurance, was implemented in Taiwan on 1 March 1995. Under the NHI, 98% of the island’s population receives all forms of health care services including out-patient services, in-patient care, Chinese medicine, dental care, childbirth services, physical therapy, preventive health care, home care, and rehabilitation for chronic mental illness. Most medical providers (93%) were under contract with the Bureau of NHI (BNHI), and those not under contract provide fewer health services. More than 96% of the population with insurance coverage through the NHI utilized health services at least one time at contracted medical institutions. Data in electronic format on daily clinic visits or hospital admissions can be obtained for each contracted medical institution. In order to be reimbursed, all medical institutions must submit their claims for billable medical services on a standardized electronic form, which includes data elements such as the date of admission and discharge, patient identification number, gender, birthday, and the ICD-9-CM diagnostic code for each admission. Therefore, the information from the NHI database appears to be sufficiently complete, reliable, and accurate for use in epidemiological studies. Daily counts of hospital admissions with a primary diagnosis of COPD  were extracted from the medical insurance files for the period 2006–2010.2) (by ultraviolet fluorescence); particulate matter (PM10) (by beta-ray absorption); nitrogen dioxide (NO2) (by ultraviolet fluorescence), carbon monoxide (CO) (by nondispersive infrared photometry), and ozone (O3) (by ultraviolet photometry) levels. However, PM2.5 was not regularly monitored. PM2.5 concentrations in Taiwan were measured continuously since 2006. PM2.5 was measured using tapered element oscillating microbalance method samplers. The availability of the monitoring network for PM2.5 provided an opportunity to investigate the impact of PM2.5 on hospital adsmissions for COPD. For each day, hourly air pollution data were obtained for all of the monitoring stations. After calculating the hourly mean of each pollutant from the six stations, the 24 h average levels of these pollutants were computed. Daily information on mean temperature and mean humidity was provided by the Taipei Observatory of the Central Weather Bureau.Six air quality monitoring stations were established in Taipei city by the Taiwanese Environmental Protection Administration (EPA), a central governmental agency in 1994. The monitoring stations were fully automated and routinely monitored five “criteria” pollutants including sulfur dioxide  was used. Because pollutants vary considerably by season, especially O3 and particles, seasonal interactions between PM2.5 and hospital admissions have often been reported. However, previous studies were conducted mostly in countries where the climates are substantially different from that in Taipei [2.5 was not considered; but temperature was used instead. The adverse health effects of each air pollutant were examined for the “warm” days (days with a mean temperature above 23 °C) and “cool” days (days with a mean temperature below 23 °C) separately. For our case-crossover analysis, we adopted a time-stratified approach . We stran Taipei ,35, whic2.5 were estimated using the odds ratio (OR) and their 95% confidence intervals (CI) which were produced using conditional logistic regression with weights equal to the number of hospital admissions on that day. All statistical analyses were performed using the SAS package . Both single-pollutant models and multi-pollutant models were fitted with a different combination of pollutants (up to two pollutants per model) to assess the stability of the effect of PM2.5. Exposure levels to air pollutants were entered into the models as continuous variables. Meteorologic variables such as daily average temperature and humidity on the same day, which might play a confounding role, were included in the model. In all analyses, we modeled the mean temperature at lag 0 as a quadratic function, mean humidity at lag 0, and pollutants as a linear function of the 3-day moving average of current and previous 2 days concentrations (lag 0–2). Inclusion of barometric pressure did not markedly change the effect estimates and therefore was not considered in the final model. OR were calculated for the interquartile difference  for PM2.5, as observed during the study period.The associations between hospital admissions for COPD and levels of PMDuring the 5 years of the study, there were a total of 22,424 hospital admissions for COPD for the 47 hospitals in Taipei city. The descriptive statistics for admissions and corresponding environmental data are shown in 10 and PM2.5 (r = 0.78), PM2.5 and SO2 (r = 0.61), PM2.5 and NO2 (r = 0.54), PM2.5 and CO (r = 0.54), SO2 and NO2 (r = 0.52), SO2 and CO (r = 0.50), and between NO2 and CO (r = 0.89). Pearson’s correlation coefficients among the air pollutants are presented in 2.5 on hospital admissions for COPD in single-pollutant models and two-pollutant models. For the single pollutant model (without adjustment for other pollutants), increased admissions for COPD were significantly associated with PM2.5 both on warm (>23 °C) and cool days (<23 °C), with an IQR increase associated with a 12% (95% CI = 8–16%) and 3% (95% CI = 0–7%) increase in COPD admissions, respectively. In two-pollutant models, PM2.5 remained significant after the inclusion of SO2 or O3 both on warm and cool days.2.5 and hospital admissions for COPD and is the first in Asia. Data demonstrated that the levels of PM2.5 were positively associated with increases in the daily number of hospitalizations for COPD after inclusion of SO2 or O3 both on warm and cool days. The observed effects of PM2.5 were not maintained in the presence of NO2 or CO. It is possible that the effect of PM2.5 might have been masked by those of NO2 and CO. This study is one of the few that investigated the association between exposure to PM2.5 on COPD admissions are rare. Belleudi et al. conducted a study in Rome, and found no evidence of an association between COPD admissions and exposure to PM2.5 [et al. [3 increase in the level of PM2.5 which is similar to their study results on COPD ER visits (4.6% for 10 ug/m3 PM2.5) [et al. reported a 1.61% (95% CI = 0.56–2.66%) increase in hospitalization for COPD per 10 ug/m3 increase in PM2.5 level [3 increment in the 3 day moving average (lag 2) concentrations of PM2.5 for warm days and cool days, respectively.Studies on the effect of PMto PM2.5 . A study [et al.  reported3 PM2.5) . Dominic.5 level . In this2.5 concentrations may be closer to personal exposure to PM2.5 in the warm season than in the cool season (better exposure assessment). The fact may attenuate the PM2.5 effect in the cool season. On the other hand, seasonal differences in air pollution mixture may also affect the effect estimates. Furthermore, compared with other studies in developed countries, our study found larger effect estimates per unit increase of PM2.5. One potential explanation for this discrepancy is that most published studies only demonstrated straightforward pooled effect estimates (lack of effect estimates stratified by season). This may conceal inherent differences between different climates and air pollution mixtures. Variations in seasonal and regional effect estimates may in part result from differences in the chemical composition of PM2.5 [In our study, effects were observed on both warm and cool days, but they were larger on warm days (effect modification). We were able to confirm that PM effects vary by season ,22. The 2.5 exposure and COPD admissions in this study. This finding is in agreement with previous studies [2.5 and COPD admissions. Researchers have suggested that PM2.5 levels represent the effective toxic fraction of PM, because PM increase and sustain oxidative stress both on the entire respiratory tract and on the systemic level, where oxidative stress induces inflammation [2.5 [The most common and consistent associations between air pollutants and hospital admissions for respiratory disease were found with PM . A signi studies ,23,27. Sammation ,55. In tammation . Animal ammation , and exaion [2.5 .2.5 components vary geographically seasonally, but typically include ammonium sulfate and nitrate, elemental carbon, carbonaceous species, carbonates, metals, and water [2.5 remains unanswered but toxicity is likely to vary between components [Numerous studies have documented an association between air pollution and increased hospital admissions in cities worldwide. Major PMnd water ,58. DespMaclure proposed the case-crossover study design as a way to study the influence of transient, intermittent exposures on the subsequent risk of uncommon acute-onset events shortly after exposure . This de2.5 levels and admissions for COPD it needs to be correlated with both variables. It is unlikely that smoking and other indoor pollutants confound the present association since day to day variations in indoor emissions, including smoking may not be correlated with PM2.5 air pollution. For a factor to confound the relationship between PM2.5 levels were assigned from fixed, outdoor monitoring stations to individuals to estimate exposure . Exposure measurement errors resulting from differences between the population‑average exposure and ambient PM2.5 levels are not avoidable. This kind of measurement error will result in nondifferential misclassification. However, this exposure misclassification is likely to cause a bias toward the null and lead to underestimates of pollutant effects [Exposure measurement error is a common concern in environmental epidemiology. PM effects ,60. Our study population is homogenous in terms of race compared with populations in other cities. This study was conducted in a subtropical city. These facts may restrict somewhat the generalizability of these findings to other locations with different meteorological and racial characteristics. Further, behavior such as air conditioning usage or time spent outdoors may affect personal exposures. This might affect the magnitude of the observed associations compared with other geographical locations.2.5 and increased hospital admissions for COPD.In summary, this study provided evidence of associations between short-term exposure to PM


Seven patients received an additional 35–50 Gy external beam radiotherapy after seed implantation, and ten patients received two to ten cycles of chemotherapy. Overall survival of the patients was calculated and prognostic factors were evaluated.Twenty-eight patients with pancreatic carcinoma who underwent laparotomy and were considered to have unresectable tumors were included in this study. Nine patients were pathologically diagnosed with Stage II disease, and nineteen patients with Stage III disease. Twenty-eight patients received intraoperative ultrasound-guided 90 higher than 110 Gy may survive for a longer period.Of the patients, 94.1% (16/17) achieved good to medium pain relief. The tumor response rate was 78.6% (22/28), and local control was achieved in 85.7% (24/28) of patients. The 1-, 2- and 3-year survival rates were 30%, 11% and 4%, and the median survival was 10.1 months (95% CI: 9.0-10.9). Analysis using the Cox proportional hazards model suggested that patients younger than 60 years and patients who received a D125I seeds. These findings need to be validated by conducting further studies with larger cohorts.I seed implantation provides a safe and effective method to relieve pain, control local tumor growth and, to some extent, prolong the survival of patients with stage II and III pancreatic disease, without additional complications. Age and accumulated dose may be factors predictive of a favorable outcome for patients with unresectable pancreatic carcinoma treated with  Pancreatic carcinoma is the tenth most common malignant tumor, but is the fourth most common cause of cancer-related deaths worldwide . Less thPancreatic carcinoma survival rates have shown little improvement over the past 30 years. Despite the introduction of new therapeutic techniques combined with aggressive modalities, such as external beam radiotherapy (EBRT), intraoperative radiotherapy (IORT) and chemotherapy, the prognosis for patients with pancreatic carcinoma remains unsatisfactory, with a 5-year survival rate less than 6% . At pres125I seed implantation as a new technique for managing unresectable pancreatic carcinoma, and demonstrated that the technique was feasible and safe [125I seed implantation, and analyzed the possible factors associated with favorable clinical outcomes.Currently, there is no consensus regarding the best therapeutic modality for unresectable pancreatic carcinoma. It is necessary to investigate novel techniques that may improve patient outcome. Wang et al. were the first group to investigate the use of intraoperative ultrasound-guided and safe . In this125I seed implantation guided by intraoperative ultrasound. The criteria of unresectable disease included vascular invasion, or vascular invasion combined with metastasis to the local regional lymph nodes. Of the twenty eight pancreatic carcinoma patients, nine were diagnosed with stage II disease, and nineteen patients had stage III disease. Summaries of the patients’ characteristics are listed in Table 125I seed implantation. All patients were evaluated for the extent of disease progression by physical examination, complete blood panel, chest X-ray, abdominal CT scans and ultrasound prior to seed implantation. This study was approved by the institutional review board and informed consent was obtained from all patients. Institutional Review Board: Peking University Third Hospital Medical Science Research Ethics Committee.Between October 2003 and August 2012, twenty eight patients with a Karnofsky performance status (KPS) score of 70 or above were identified. Of these twenty eight patients, 39% (10/28) had jaundice, 60% (17/28) suffered pain, 11% (3/28) had intestinal obstruction and 93% (26/28) experienced weight loss. These patients were diagnosed with unresectable pancreatic carcinoma by surgeons carrying out a laparotomy, and received 90 of 60–163 Gy (median 120 Gy) for 125I seed irradiation could be calculated. Then the system figured out the required number of 125I seeds to be implanted. The D90 was defined that at least 90% of the tumor volume received the reference dose  had a half-life of 59.4 days with a low energy level of 27.4 KeV and a half-value layer of 0.025 mm of lead. A computerized treatment planning system  was used for dose calculations.Computerized tomography (CT) scans were taken 1–2 weeks before seed implantation to evaluate detailed tumor location and volume of patients. Images of pancreatic carcinomas were obtained at 5 mm intervals. The gross tumor volume (GTV) was outlined by radiation oncologists and surgeons on each image in consultation with one another. The planning target volume (PTV) included GTV plus 0.5-1.0 cm peripheral tissue. These traces were digitized and scanned to define the tumor volume, from which the D125I seeds were implanted using a Mick applicator following insertion of the needles, and the spacing for seeds in the same needle is 1 cm [125I seeds implanted ranged from ten to seventy five; the median number was thirty five. The specific activity of 125I seeds ranged from 0.40 to 0.60 mCi per seed, and the total isotope radioactivity implanted ranged from 4 to 37.5 mCi. An omental fat pad was placed over the implanted volume to protect the gastric and transverse colon mucosa from excessive irradiation.Following collection of an intraoperative biopsy to establish the diagnosis of pancreatic cancer, tumor volume was measured during laparotomy by intraoperative ultrasonography utilizing a megahertz linear probe. Guided by ultrasound, 18-gauge needles were implanted into the mass and spaced at intervals of 1.0 cm in a parallel array, extending at least 0.5-1.0 cm beyond the margins of the pancreatic lesions. During the placement of the needles, care was taken to avoid the needles penetrating the pancreatic duct, small blood vessels, and the adjacent transverse colon by ensuring placement at least 1 cm from these tissues.  is 1 cm . The num125I seed implantation. The total dose of EBRT ranged from 35 to 50 Gy at 1.8-2.0 Gy per fraction. Postoperative chemotherapy was recommended for all patients on an adjuvant or palliative basis, but only ten patients received chemotherapy consisting of gemcitabine or paclitaxel and completed two to six cycles. The remaining patients refused EBRT or chemotherapy following seed implantation.EBRT was generally recommended for all patients as an adjuvant therapy, but only seven patients received EBRT 4–6 weeks after Tumor response was assessed using WHO criteria . In briePain is one of the most common clinical symptoms of pancreatic carcinoma. Pain intensity was evaluated and graded by the Numerical Rating Scale (NRS). NRS score 1–3 was defined as mild pain, NRS score 4–6 was defined as moderate pain and NRS score 7–10 was defined as severe pain . A good Patients were evaluated by radiation oncologists and surgeons one month after seed implantation. Regular items included physical examination, complete blood panel, chest X-ray, abdominal CT and ultrasound. Then, a clinical consultation was provided, followed by evaluation every 2–3 months or sooner if a new clinical sign or symptom appeared. Survival was calculated from the date of diagnosis to the date of death, or last follow-up. Local recurrence was defined as tumor progression within the implanted area or surrounding regions according to CT images. Local recurrence and distant metastases were scored until patient death, and censored thereafter.p value of <0.05.Overall survival rates were estimated using the Kaplan-Meier method, and deaths for any reason were scored as events. The impact of different factors on the survival curves was analyzed using the log-rank test and Cox proportional hazards model, that were frequently used in single factor analysis and multiple factor analysis. SPSS version 16.0 was used for statistical analysis, with the level of significance defined as a In our study, the tumor response rate was 78.6%, with an overall local control rate of 85.7% 24/28)  achieved good response. Three patients suffering severe pain and five patients with moderate pain were all reported no pain after treatment. An additional 47% (8/17) of patients achieved medium response. Six patients with severe pain and one patient with moderate pain were reported only mild pain following treatment. Only one patient continued to suffer moderate pain after treatment. The majority of patients experienced some relief from pain within one week following seed implantation.Pain is one of the most common clinical symptoms of pancreatic carcinoma. 60% (17/28) of patients were suffering pain prior to treatment, and 94.1% (16/17) of patients achieved a good or medium response after There were few toxicity and complications, and no patients died during the perioperative period. Chylous fistula was observed in one patient (4%). Gastric ulcer was observed in one patient (4%) who underwent seed implantation and EBRT. Two patients (7%) experienced radiation enteritis and ten patients (36%) experienced transient fever. In addition, in each of two (7%) patients, three seeds were found to have migrated to the liver. However, no side effects were observed in the 12 months post-treatment.90 higher than 110 Gy , and patients younger than 60 years may survive longer. The median survival of patients who actually received a D90 higher or lower than 110 Gy was 11 months (95% CI: 9.3-12.6) and 8 months (95% CI: 3.9-12.0), respectively, p < 0.001. The median survival of patients younger than 60 years was 10 months (95% CI: 8.0-11.9), compared with 9 months (95% CI: 8.0-9.9) for patients over 60 years old (p = 0.035). The outcome of patients with pancreatic carcinoma in the head of the pancreas and jaundice may be poor. The median survival time of patients with cancer in the head of the pancreas was 9 months (95% CI: 8.3-9.7) compared with 11 months (95% CI: 9.3-12.6) for patients whose tumor was situated outside of the head of the pancreas (p = 0.15). The median survival of patients with and without jaundice was 9 months (95% CI: 8.3-9.6) and 11 months (95% CI: 9.4-12.5), respectively (p = 0.09). Patients who achieved CR and received adjuvant EBRT may survive longer. However additional patients should be enrolled to verify these observations. The median survival of patients achieving CR or not was 24 months (95% CI: 7.9-40.0) and 9 months (95% CI: 8.0-9.9), respectively (p = 0.05). However, only three patients achieved CR, with overall survival of 14, 24 and 28 months, respectively. The median survival of patients receiving adjuvant EBRT or not was 13 months (95% CI: 8.3-17.6) and 10 months (95% CI: 9.0-10.9), respectively (p = 0.24). However, only seven patients received adjuvant EBRT, and six of these patients were younger than 60 years. Gender, adjuvant chemotherapy, tumor volume and CA199 level before and after the operation did not impact the clinical outcome (p > 0.05). The result of the Cox proportional hazards model suggested that a D90 higher than 110 Gy was an independent, favorable prognostic factor comparing with lower than 110 Gy (p = 0.001), and the relative risk ratio was 0.21 (95% CI: 0.08-0.57). The fitted curve is shown in Figure p = 0.002), and the relative risk ratio was 0.34 (95% CI: 0.13-0.91). The fitted curve is shown in Figure Multiple factors that may affect overall survival were analyzed. Log-rank single factor analysis suggested that patients who actually received a DPancreatic cancer has an appalling prognosis, especially for patients with unresectable tumors at the time of diagnosis, which represents more than 80% of patients. Therefore the treatment of unresectable pancreatic cancer continues to be a major challenge. In approximately 30% of patients with unresectable tumors, the lesions remain locally advanced without evidence of distant metastases at autopsy . TherefoRadiation techniques such as three-dimensional conformal radiotherapy, intensity-modulated radiotherapy (IMRT), stereotactic body radiation therapy (SBRT), intraoperative radiation therapy, and low-dose rate (LDR) or high-dose rate (HDR) radiation have all been used in the treatment of locally advanced pancreatic cancer. However, the clinical outcomes are unsatisfactory. There is evidence that common external beam radiation with or without chemotherapy can achieve a median survival time of 8.2-14.8 months, with the incidence of grade III to IV complications between 10% and 25% -16. The 125I seed continuous low dose rate irradiation may be beneficial to pancreatic carcinoma. Wang et al. reported that 125I seeds irradiation could induce higher apoptotic rates of PANC-1 pancreatic cancer cells, which led to programmed cell death [125I seed continuous low dose rate irradiation inhibited pancreatic cancer tumor growth and changed DNA methyltransferases expression patterns [125I seed continuous low dose rate irradiation from beach to bedside.Recent years, there were some basic research indicated that ll death . Ma et apatterns . Similarpatterns ,28. Basi125I seed implantation, intraoperative ultrasound-guided implantation of 125I seeds for unresectable pancreatic carcinoma is feasible and safety, especially for those centers who do not have IORT equipment. 125I seeds were selected as the radioactive source, due to the half-life of the isotope of 59.4 days [125I seed implantation for the treatment of pancreatic carcinoma, enrolled ninety eight patients, and achieved a median survival time of 7 months in 1975 [125I seed implantation was comparable with other techniques in patients with locally advanced pancreatic carcinoma [125I seed implantation to manage unresectable pancreatic carcinoma, and demonstrated that it was a feasible and safe technique [The advantage of permanent interstitial radioactive seed implantation into the tumor site is the ability to deliver a high dose of irradiation to the tumor while minimizing relative exposure to the surrounding area. In some medical centers who have skillful surgeons, radiation oncologists and license of 9.4 days . The tec9.4 days . Hilaris in 1975 , with on in 1975 . These rarcinoma . Wang etechnique -33.The limitation of permanent interstitial radioactive seed implantation in pancreatic cancer is the high rate of perioperative morbidity and mortality, since most of the earlier radioactive seed implantation techniques were performed by eye during surgery. In a previous study using eye guided implantation, the perioperative mortality rate was 16% to 25% due to acute pancreatitis, fistulization, and abscess formation . Probabl90 higher than 110 Gy and patients younger than 60 years may survive longer (p < 0.05). The outcome of patients with pancreatic carcinoma in the head of the pancreas or who have jaundice may be poor. However, additional patients should be observed to confirm these findings. Gender, adjuvant chemotherapy, tumor volume and CA199 level before and after the operation did not impact the clinical outcome (p > 0.05). Multivariate analysis suggested that a D90 higher than 110 Gy and an age younger than 60 years were independent, favorable prognostic factors with a relative risk ratio of 0.21 and 0.34, respectively. Therefore, we recommend that the optimal dose for 125I seed implantation in patients with unresectable pancreatic cancer is at least 110 Gy.The data indicate that younger patients with good performance status, or treatment with gemcitabine- or capecitabine-based chemotherapy were favorable prognostic factors -38. Mult125I seed implantation is a safe, effective radiation technique for the treatment of unresectable pancreatic cancer. The technique provides satisfactory distribution of seeds within the tumor mass and achieves favorable clinical outcomes with acceptable complications. Additional studies with larger patient cohorts are now required in order to verify these results.Intraoperative ultrasound-guided permanent 125I: Iodine-125; LDR: Low-dose rate; HDR: High-dose rate; IMRT: Intensity-modulated radiotherapy; EBRT: External beam radiotherapy; IORT: Intraoperative radiotherapy; GTV: Gross tumor volume; PTV: Planning tumor volume; SBRT: Stereotactic body radiation therapy; CR: Complete response; PR: Partial response; PD: Progressive disease; NRS: Numerical rating scale; KPS: Karnofsky performance status; RR: Relative risk.The authors declare that they have no competing interests.JJW conceived, designed, coordinated the study and wrote the paper; HW, YLJ, JNL, SQT and YG contributed to the data collection and performed the statistical analysis; WQR and DRX performed the research. All authors read and approved the final version of the manuscript.Characteristics of Patients and Treatment.Click here for fileResults using intraoperative ultrasound‒guided implantation of 125I seeds for patients with locally advanced unresectable pancreatic cancer.Click here for file