Introduction: Patients with low serum albumin and abnormal BMI may be at the risk of death and other complications after surgery. This could be remarkable in patients with coronary arteries bypass graft surgery. Therefore, we decided to evaluate the impact of these factors associated with survival and outcome after cardiac surgery.Methods: A cross-sectional study was performed from 2009 until 2012 on 345 patients who underwent coronary artery bypass grafts. Also Patients were monitored for a year. Patients’ information was collected and then the patients were analyzed for body mass index (BMI) and serum albumin and their effects on postoperative outcomes. P value <0.05 was considered statistically significant.Results: Mortality after CABG operation was not of a significant relation in patients with low BMI (BMI <20), normal and high (BMI> 30). Obese patients are more susceptible to myocardial infarction in postoperative period (P=0.02). Pneumonia after surgery in these patients was more common than others (P= 0.023); however, low serum albumin was significantly associated with mortality following operation (P<0.001). Reoperation due to bleeding (P<0.001) and required mechanical ventilation for more than a day (P=0.019) were significantly associated with low serum albumin.Conclusion: In conclusion, the high or low BMI alone did not increase mortality after cardiac surgery. However, postoperative morbidity in obese patients may be greater than others. Low serum albumin may increase the risk of mortality and postoperative complications as well. Therefore, it seems ameliorating serum albumin can be effective more than body mass index in improving the outcome of patients after CABG surgery. Long-term survival after CABG is excellent: 5-year survival of 90% and 10-year survival of 75 to 90% depending on comorbidities.3 Intensive medical therapy to control diabetes, hypercholesterolemia, and hypertension and smoking significantly improve long-term survival. According to data in STS database (Society of Thoracic Surgeons), the risk of mortality associated with CABG surgery reaches to 1.9% and rises to 15% with severe complications.3Coronary artery disease is the most common cardiac pathology which cardiovascular surgeons deal with. The etiology of coronary artery disease is atherosclerosis basically.3Risk of bleeding requiring reoperation is 1.8%, MI 0.9% and the probability of any neurological complications  1.6%. Also, there is 1.1% risk for permanent stroke.4 In a series of studies, BMI was demonstrated to be of a significant effect on the duration of hospitalization of the patient in the ICU and the surgery department. Patients with weight gain and obesity had shorter duration of stay in the ICU than patients with normal BMI and obesity did not have any effects on increase of morbidity and other side effects during operation compared with normal weight.6Engeiman et al. reported both low body mass index (BMI) and hypoalbuminemia as reason of increased mortality and postoperative complications after cardiac surgery. Thinnest patients had the highest risk factors for postoperative complications.9 Habib et al concluded that high rate of deviation in BMI compared to the normal BMI cause direct increase in morbidity and also decrease in long term survival.10 Severe obesity (BMI> 40) is specifically related to undesirable consequences escalating duration of hospitalization after CABG.14 On the other hand, there is belief that obese patients have better consequences and higher survival in hospital than patients with normal BMI.16It has been suggested that a lot of attention should be paid to the heart surgery of patients with low BMI due to their being prone to the consequence after the surgery.17Kesek et al. concluded that cardiac surgery patients who have low BMI have raised mortality rates and low serum albumin levels expand the risk of infection after surgery.A cross-sectional and descriptive-analytic study was conducted in Jorjani heart surgery center of Shahid Mohammadi hospital on patients with CABG by using left internal mammary artery (LIMA) and saphenous vein graft with Cardiopulmonary Bypass (CPB) from June 2009 to August 2012 for 38 months. First of all, patients’ demographic data including patient age, sex, place of birth, place of residence, weight and height as well as laboratory data on admission and risk factors that might affect outcome of the disease were collected. Patients were monitored to evaluate the physical condition of patients and postoperative complications for one year. Some of patients who could not be accessed were excluded from the study.2, normal 20-30 kg/m2 and high 30< kg/m2). Serum albumin levels were divided into three groups . Data were analyzed using SPSS. 20 and Chi-square test to examine the relationships between variables. P value less than < 0.05 was considered statistically significant.Patients were sorted in three categories by BMI .Overall, 345 patients with coronary artery bypass graft (CABG) were studied; 59% (203 subjects) were male and 41% (142 subjects) were female. Average age of the patients was 60.7 years; the minimum age was 30 years and maximum 86 years. Of the studied patients, 16.4% aged less than 50 years, 73.4% between 50 and 75 years and 10.2% were over 75 years of age (with the mean weight of 61 kg ranging from 34 to 110 kg). BMI of the patients was between minimum of 13.48 kg/mThe mean serum albumin levels was 3.72 g/dl; 0.4% of patients had levels of less than 2.5 g/dl, 36.2% of patients between 2.5 and 3.5 g/dl and 43.4% of patients greater than 3.5 g/dl serum albumin. In terms of gender, 31.9% of females and 39.4% males had low serum albumin levels (2.5-3.5 g/dl). There was no significant relation between gender and serum albumin levels .2) was observed in 15.2% of females, and 22.7% of males. Furthermore, 8.7% of females and 3.5% males had high BMI (>30 kg/m2). There was a statistically significant relationship between BMI and sex (P =0.04). There was no significant association between gender and mortality (P=0.83) (Low BMI (< 20kg/m(P=0.83) .2 died during or shortly after surgery. There was no significant relation between these variables (P=0.20) (2) and high BMI (>30kg/m2) were identified in 14.3% and 11.1% of patients, respectively. However, there was no significant relation between variables.Low serum albumin levels (2.5-3.5g/dl) were reported in 51% of patients with low BMI and 28.6% of patients with high BMI. While 71.4% of patients with high BMI and 49% of patients with low BMI had serum albumin levels higher than 3.5 g/dl. There was no significant relation between BMI and serum albumin levels (P=0.20) . Of note(P=0.20) . Lower sOnly one patient had low serum albumin levels (<2.5 mg/dl); so, we did not include him in later steps. Notably, this patient required reoperation due to bleeding after surgery and stayed in the ICU for more than 3 days. . Of pati2) and high BMI (> 30 kg/m2), 22.7% and 21.1% required reoperation because of bleeding, respectively. The relationship was not significant (P= 0.50) (Of patients with low BMI (<20 kg/mP= 0.50) .Significant association did not exist between BMI and serum albumin levels in patients with CABG postoperative complications such as deep sternal region infection, leg infection, cerebrovascular accident/ transient ischemic attack, low cardiac output, sepsis, or requiring ICU more than 3 days .2) patients were affected by MI or pneumonia after operation while patients with low BMI (<20 kg/m2) did not develop these complications. There was a significant relationship between variables (P=0.02)  . Mechani(P=0.02) . More th(P=0.02) .12.7% of patients with low serum albumin levels (2.5-3.5g/dl) died during or after surgery. However, none of the patients with normal serum albumin levels (>3.5 g/dl) had such a condition. There was significant relation between variables. (Table 2).2) and 16.7% patients with high BMI (> 30 kg/m2) died during or after surgery. But the relationship between them was not significant . In this study, females were significantly more obese than men and males contributing to the majority of thin people. However, low serum albumin did not have association with gender. Moreover, mortality after CABG surgery was not affected by gender.2) compared to patients with low BMI (<20 kg/m2) were at higher risk for MI after CABG which could increase mortality and adverse outcomes after the operation. This study showed that the risk of pneumonia after CABG increases in obese patients. However, patients with low BMI are less prone to this complication. The study did not find evidence of a direct effect of low or high BMI on postoperative complications including prolonged hospitalization or hospitalization in the intensive care unit for long time, sepsis, lower cardiac output, stroke, surgery site infection and reoperation due to bleeding.Old age had relation with decreased serum albumin and BMI. Majorities of the elderly patients were thin and had low serum albumin levels. However, age is not a risk factor for increased mortality after cardiac surgery. The simultaneous presences of other risk factors are needed for increased morbidity and mortality. Unlike the study of Kesek et al. (17), in our study obese patients  had higher mortality risk after cardiac surgery. These patients were also at higher risk of postoperative bleeding requiring reoperation after CABG. Low serum albumin levels are independent risk factor that increases the need for mechanical ventilation for more than 1 day after CABG despite correcting it before operation.In contrast with some of the previous studiesUnlike other studies, low BMI and high BMI did not increase mortality after CABG in our study. Patients with a higher BMI are at increased risk of complications after heart surgery and their outcomes are worse. In patients with low serum albumin levels, mortality after CABG is high. These patients also have higher postoperative complications. Values of albumin levels are more prognostic for patient outcome and are of further importance.The study was approved by the Ethics Committee of the University.Authors declare no conflict of interest in this study.


Observing the fast during the holy month of Ramadan is one of the five pillars of Islam. Although pregnant women and those with pre-existing illness are exempted from fasting many still choose to fast during this time. The fasting behaviours of pregnant Muslim women resident in Western countries remain largely unexplored and relationships between fasting behaviour and offspring health outcomes remain contentious. This study was undertaken to assess the prevalence, characteristics of fasting behaviours and offspring health outcomes in Asian and Asian British Muslim women within a UK birth cohort.Prospective cohort study conducted at the Bradford Royal Infirmary UK from October to December 2010 comprising 310 pregnant Muslim women of Asian or Asian British ethnicity that had a live singleton birth at the Bradford Royal Infirmary. The main outcome of the study was the decision to fast or not during Ramadan. Secondary outcomes were preterm births and mean birthweight. Logistic regression analyses were used to investigate the relationship between covariables of interest and women’s decision to fast or not fast. Logistic regression was also used to investigate the relationship between covariables and preterm birth as well as low birth weight.Mutually adjusted analysis showed that the odds of any fasting were higher for women with an obese BMI at booking compared to women with a normal BMI, (OR 2.78 (95% C.I. 1.29-5.97)), for multiparous compared to nulliparous women(OR 3.69 (95% C.I. 1.38-9.86)), and for Bangladeshi origin women compared to Pakistani origin women (OR 3.77 (95% C.I. 1.04-13.65)). Odds of fasting were lower in women with higher levels of education (OR 0.40 (95% C.I. 0.18-0.91)) and with increasing maternal age (OR 0.87 (95% C.I. 0.80-0.94). No associations were observed between fasting and health outcomes in the offspring.Pregnant Muslim women residing in the UK who fasted during Ramadan differed by social, demographic and lifestyle characteristics compared to their non-fasting peers. Fasting was not found to be associated with adverse birth outcomes in this sample although these results require confirmation using reported fasting data in a larger sample before the safety of fasting during pregnancy can be established.The online version of this article (doi:10.1186/1471-2393-14-335) contains supplementary material, which is available to authorized users. Annual fasting during the holy month of Ramadan is one of the five pillars of Islam. During Ramadan all able bodied Muslims abstain from food, fluids, smoking and oral medications between sunrise and sunset . Muslim Contemporary evidence on Ramadan fasting behaviours undertaken by pregnant women in the UK is scarce, with the last survey published in 1982 . As objeRecent data from the 2011 UK census shows that the Muslim population of the UK now comprises 4.8 per cent of the population up from three per cent in the previous 2001 census and locally in Bradford 24.7 per cent of the population reports their religious group as Islam . Given tWe used data from a sub cohort of the Born in Bradford (BiB) birth cohort study to explore the Ramadan fasting behaviours of pregnant Muslim women and associated birth outcomes.Born in Bradford (BiB) is a longitudinal multi-ethnic birth cohort study investigating the impact of environmental, psychological and genetic factors on maternal and child health and wellbeing . BradforBetween October and December 2010, a consecutive sample of 310 pregnant women who reported their ethnicity as Asian or Asian British and reported their religion as Islam were approached and agreed to participate in this study. We included results from all women who had live singleton births with a linked maternity record resulting in an eligible sample of 300 women for this study. Ten women were excluded from the analysis, n = 1 did not have linked birth information for, n = 7 excluded as had multiple births, n = 2 did not have a live birth.th of August to 8th of September, a total period of 29 days with fasting times of up to 18 hours per day. The first question asked women if they had fasted during Ramadan in their pregnancy this year; response options were (fully- full 29 day period), yes  or not fasting and secondly asked pregnant women how many days they had fasted. We explored the effect of fasting by grouping fasting behaviour into a binary, fasted not fasted classification. To test for a dose response effect of fasting we also examined the effect of fasting as a categorical variable grouped as none, 1–10 days, 11–19 days, 20–29 days.In addition to the baseline questionnaire, participants in this sub study were asked two extra questions relating to their fasting behaviour during the preceding Ramadan. In 2010, Ramadan occurred between 11The primary outcome was fasting behaviour, defined as fasting or not fasting. Secondary outcomes of this study were preterm delivery and birth weight as they had previously been reported to be associated with Ramadan fasting –4, 8. Prstandard minimum level of education when leaving school), A level equivalent, Higher than A level, Other), mother living in an extended family (yes or no) and consanguinity (in consanguineous relationship vs not in consanguineous relationship). We also explored markers of health during pregnancy including gestational and pre-existing diabetes, pregnancy induced hypertension (defined as having a blood pressure higher than 140/90 measured at two or more periods at least 6 hours apart) and pre-eclampsia (defined as defined as proteinuria (+0.3 gms with blood pressure >/=140/90 after 20 weeks of pregnancy on more than one occasion) which were all categorised as yes or no to ascertain whether women with health problems took the option of exemption from fasting.A priori we selected covariables that are known to be associated with the outcomes of interest and/or hypothesised to be associated with the decision to fast. These included trimester exposed to fasting, booking BMI , maternal age (mean centred), parity , ethnic origin , marker of acculturation (born in the UK or migrated to the UK aged five or less vs migrated to the UK aged greater than five years), smoking status (yes or no), employment status , marital status , maternal education  qualification, 5 GCSEs , of all pregnant women reported fasting during Ramadan in 2010. Of these women who fasted, this was undertaken partially by 28 per cent and for the full period of Ramadan by 14 per cent of pregnant women. Of the cohort who chose to fast, most were fasting in their first  and second trimesters of pregnancy . Table 28, of alNext the univariate and multivariate relationship of covariables and fasting behaviours were investigated with non-fasters comprising the reference category. These relationships are shown below in Table The results of univariate analyses showed a higher odds of fasting for women with an obese BMI at booking compared to women of a normal BMI OR 2.44 (95% C.I. 1.31-4.57), women who moved to the UK aged over five compared to women who moved prior to age five or were born in the UK, OR 1.59 (1.00-2.51), higher in women who were in a consanguineous relationship compared to those not in consanguineous relationships, OR 1.89 (95% C.I. 1.19-3.02), and a higher odds of fasting with parity of three or greater compared with nulliparous women OR 1.95 (95% C.I. 1.02-3.71), whereas women who had educational qualifications of greater than A level were less likely to fast compared to women with less than 5 GCSEs, OR 0.35 (95% C.I. 0.18-0.67) as were older women compared to younger women OR 0.95 (95% C.I. 0.90-0.99).Adjusted analyses were conducted including all variables where covariates had p values greater than 0.2. In these adjusted analyses higher maternal age, OR 0.87 (0.80-0.94), and highest educational qualification greater than A level OR 0.40 (0.18-0.91) remained significantly associated with lower odds of fasting. Likewise higher parity and obese BMI remained significantly associated with higher odds of fasting. Women with a parity of either two or three or greater had a higher odds of fasting, OR 3.69 (95 C.I. 1.38-9.86) and OR 3.99 (95 C.I. 1.39-11.49) respectively, compared to women who were nulliparous and women with an obese BMI had an odds of fasting 2.78 (95% C.I. 1.29-5.97) that of women with a normal BMI at booking. In this final adjusted analyses maternal employment, migration status and consanguinity were no longer significantly associated with odds of fasting. Bangladeshi ethnicity was however found to be associated with higher odds of fasting 3.77 (95% C.I. 1.04-13.65).We also examined the relationship between fasting categories (day of fasting) and covariables, .Born in Bradford is only possible because of the enthusiasm and commitment of the Children and Parents in BiB. We are grateful to all the participants, health professionals and researchers who have made Born in Bradford happen.Table S2. Adjusted relationship of covariables to fasting behaviour. (DOC 98 KB)Additional file 1: Table S1.: Unadjusted relationship of covariables to fasting behaviour.


To evaluate the clinical usefulness of lung biopsy in ventilated patients admitted to an Intensive Care Unit.Retrospective descriptive study that included 16 ventilated patients admitted to the ICU, which underwent a lung biopsy between 2008 and 2013. Demographic data, reason for admission, comorbidities, APACHEII, SOFA, SAPS3, reason for biopsy, clinical data, laboratory results, bronchoalveolar lavage (BAL), radiological pattern and histology, were analyzed. Changes in treatment generated by these results and their impact on prognosis were also analyzed.The average age of the population was 60 ( ± 13) years. 68.8% of patients were male. Most patients were admitted for severe CAP (62.5%). The most frequent comorbidities were malignancy and immunosuppression (25%) with APACHE 17 ( ± 5) SAPS3 57 ( ± 14) and SOFA 5 ( ± 2). The main reason for lung biopsy was nonresolving acute respiratory distress syndrome . 62.5% of biopsies were opened, 25% were transbronchial and 12.5% were obtained with transthoracic punction. Laboratory results and BAL were inconclusive and the most frequent tomographic pattern was alveolar damage and ground glass (56.2%). The main results of biopsies were idiopathic interstitial disease (56%), tumors (25%) and other processes (19%). In 55.5% of cases the histologic diagnosis led to changes in treatment (start corticosteroids or stop antibiotic). The most common complication related to the procedure was pneumothorax (25%). Intra-ICU mortality was 50% and within patients who died, 75% had neoplastic disease and 25% had interstitial disease.Open lung biopsy confirmed the diagnosis in all cases and caused a change in treatment in 50% of them. The most frequent diagnosis was idiopathic interstitial lung disease, which appears to have a better prognosis than neoplasic pathology. In the group of patients with nonresolving ARDS, Lung biopsy could be a useful and safe procedure to guide the treatment and prognosis.


Graves’ disease is the most common cause of thyrotoxicosis in children. Prepubertal children are the most difficult to treat with remission attained in less than 15% .Objective: To characterise clinical features and review treatment outcome among children with very early onset Graves’.Retrospective medical record review of patients diagnosed with Graves’ disease at age less than 8 years, who received treatment in our department in the last 14 years.Sixteen patients  were identified with median age at diagnosis of 4.96 years (range 2.5-7.83). Presenting symptoms were hyperactivity, weight loss, poor sleep and diarrhoea. They had predominant non-Anglo-Saxon ethnicity. Significant co-morbidities were- Down syndrome , juvenilOur cohort had 16 patients diagnosed with Graves’ at a median age of 4.96 years. Overall remission for those with more than 30 months follow-up is 58.3% (7/12), at a median age of 10.13 years. Thyroidectomy had a remission rate of 100%, ATD’s alone of 33.3% and one dose of radioactive iodine ablation of 25%.


Malignant hyperthermia (MH) is a rare disorder, occurring in 1 per 5,000 to 1 per 50,000 – 100,000 anaesthetic procedures and is usually fatal if untreated. Relapse occurs in 23% of patients in spite of appropriate management. Since emergency treatment is required, few reports document the time course of events relative to treatment.2 subsequently remaining stable for 2 hours. However, this increased to 10kPa and the patient began to sweat. The patient’s temperature rose from 35.5°C 15 minutes after the start of the procedure to 37.9°C after 2.5 hours, but 15 minutes later the patient’s temperature was 38.9°C. MH was diagnosed and dantrolene 380mg administered. Minute ventilation was increased to 12 litres FiO2 100%. Cooling was performed with cold intravenous Ringer Acetate and surface cooling with ice. After 25 minutes the temperature was 37.6°C. The patient remained on the ventilator for 11 hours after anaesthesia. There was mild recrudescence at approximately 6 hours, with blood pH gradually falling from 7.43 to 7.31, and pCO2 increasing from 4.9 to 6.8. A 200mg dantrolene infusion was therefore administered over 2 hours, prior to extubation of the patient, such that the total dose of dantrolene administered was 580mg . When the patient came round he reported severe muscle pain. With regard to surgery, the mandible sagittal split was performed, but the maxillary surgery was cancelled, leaving the patient unable to close his mouth or bite. Over the following 2 weeks, prior to the second surgery, the patient was only able to drink and lost 6kg. Second surgery was performed in trigger free anaesthesia without problems. In vitro contracture test revealed MH susceptible results . The patient has p. 552 Arg>Trp mutation in RYR1.The patient, a 19 year old healthy male, who suffered childhood asthma, was anaesthetised for a planned mandible sagittal split and bimaxillar osteotomia due to prognathia. Anaesthesia was induced with propofol 140mg and suxamethonium 100mg was administered for muscle relaxation. Relaxation was not optimal but intubation was performed without problems. Anaesthesia was maintained with remifentanil (0.6-2.3µg/kg/min) and desflurane (4.9-7vol%). After 15 minutes the airway pressure was 30mbar, which was initially interpreted as broncho-obstructivity due to his childhood asthma, however, it was probably a sign of muscle rigidity. The patient was given minute ventilation at 8.2 litres, with pCOThis report describes the time course for the onset of clinical features of MH, and associated changes in laboratory parameters, and during relapse. It clearly demonstrates the need for, and efficacy of, dantrolene, when used immediately. Since the introduction of intravenous dantrolene, mortality from MH has fallen from 80% to less than 5%. The European Guidelines for the management of a MH crisis recommend the immediate use of dantrolene sodium in combination with other symptomatic treatments as soon as a MH crisis is suspected, and recognise that an adult patient requires up to 50 vials for effective treatment.


Real clinical setting data about onabotulinumtoxinA treatment on chronic migraine are poor, especially in patients with medication-overuse headache (MOH) and ≥ 65 years old, as well as data on predictors of responsivity. W present results on chronic migraine patients treated at the Padua Headache Centre from April 2014 to March 2015.By compiling a headache diary, efficacy parameters (mean reduction of headache days and hours) were evaluated at 90 days after the first cycle. We analyzed also: 30% and 50% response rates and the percent of first-time responders to II cycle; association with headache related symptoms and comorbidities .Forty patients were evaluated  of which 37/40 (93%) with MOH. At 90 days after the first cycle headache diary documented a significant mean reduction of headache days , of the total hours of headache , of the hours of moderate pain  and severe pain , of the consumption of triptans  and associations . The 8 patients ≥65 years old did not present a significant reduction of efficacy parameters vs younger patients. 50% and 30% response rate was respectively 22.5% and 38% for at least one efficacy parameter, 15% and 25% for headache days, of 20% and 35% for hours, 12.5 and 23% for both parameters. Percent of “first-time 50% responders” was 15.8% and 10.8% respectively for headache days and hours; percent of “first-time 30% responders” was 26.3% and 15.8%. Cluster analysis showed a higher severe headache share and a lower share of mild headache in responsive patients vs non responsive: 146.7 (26.3%) vs 119.1 (17.6%) severe pain hours, 162.2 (29.1%) vs 287.1 (41.1%) mild pain hours. ANOVA analysis did not show significant association between responsivity and headache symptoms or related comorbidities, except for a lower response trend of depression/anxiety at limit of significance (p = 0.07).OnabotulinumtoxinA treatment appears useful also in a clinical setting with high presence of MOH. Responsive patients are <65 years old and have a higher frequency of severe headache and a lower share of mild headache. Depression/anxiety disorders are associated also to a lower responsiveness trend at limit of significance.Written informed consent to publication was obtained from the patient(s).The principal author declares that there is no conflict of interest.


Aim. To prove the safety and feasibility of minimally invasive (laparoscopic and robotic) colorectal resection in kidney recipients by evaluating the technical protocol and reviewing short- and long-term outcomes. Methods. Between May 2007 and August 2012, a retrospective review of ten kidney transplant patients diagnosed with colorectal cancer was evaluated for technical tips, short- and long-term outcomes. Results. The mean patients' age was 56.8 ± 9.91 years and 50% of them were male. Anterior and low anterior resections were performed in 40% of the patients each; 20% and 10% of the patients underwent right and left hemicolectomy, respectively. Most (90%) procedures were performed laparoscopically and 10% were performed robotically. No open conversions. Mean operating time was 192.5 ± 15 min, blood loss was 30 ± 50 mL, and mean hospital stay was 9.7 ± 5.5 days. Two (20%) patients had postoperative complications: wound seroma and chyloperitoneum. Over a mean follow-up period of 31.4 ± 21.57 months, no mortality or kidney rejection occurred. Among the six patients followed up for a mean of 43.5 ± 9.84 months, 83.3% were 3-year disease-free and the overall survival rate was 100%. Conclusion. Minimally invasive colorectal resection is likely to be safe and feasible, with fewer complications and acceptable short- and long-term outcomes, in kidney transplant recipients. Kidney transplant recipients not only have numerous comorbidities associated with renal failure, but also often have additional problems due to chronic immunosuppression –3. The sAlthough open colorectal resection has been practiced for many years in kidney recipient patients, the minimally invasive procedure has been developed and is gaining popularity. Multiple randomized controlled trials have proven that minimally invasive surgery yields better short-term outcomes than open colorectal surgery in terms of reduced intraoperative bleeding, postoperative pain, and hospital stay, as well as a lower incidence of infection and respiratory complications, with equivalent long-term outcomes , 5. HighThe aim of this study was to prove the safety and feasibility of laparoscopic and robotic colorectal resection in kidney transplant recipients by evaluating the technical protocol and the short- and long-term outcomes.P value ≤ 0.05 was considered statistically significant.This retrospective review of all kidney transplant recipients diagnosed with colon or rectal cancer who received laparoscopic or robotic resection was conducted between May 2007 and August 2012 at Yonsei University College of Medicine, South Korea. Short- and long-term outcomes were evaluated and technical methods were assessed. Data were analyzed using the SPSS statistical program . A Technique. All patients received 4 liters of GoLYTELY  preoperatively to evacuate the intestine. Antibiotics and a stress dose of steroids of 100 mg were given on induction of anesthesia and continued postoperatively with tapering dose of steroid. All kidney transplants were performed at the right iliac fossa.A main concern in laparoscopic and robotic colorectal resection is accurate and safe port placement to avoid injury to the transplanted kidney.2 to 12–14 mmHg pressure. The kidney was shifted posterolaterally to provide adequate space for the working ports  patients had hypertension, three (30%) had diabetes mellitus, one patient had a history of hepatitis, and one had a history of chronic pulmonary tuberculosis. The main reasons for kidney failure were the hypertension and diabetes mellitus. No patient had a history of liver failure or transplant. The American Society of Anesthesiologists scores were II in 60% of patients and I and III in 20% of patients each.Between May 2007 and August 2012, 782 patients underwent kidney transplantation. Ten of these recipients were diagnosed with colon or rectal cancer and underwent minimally invasive surgical resection. Five (50%) patients were males; the mean patient age was 56.8  years, and the mean body mass index was 22.4 (range 20.5–26.4) kg/m via biopsy. Synchronous tumors were identified in one case. Preoperative stages were I and II in 40% of the patients and III in 10% of the patients. No tumor invasion or extension beyond the mesorectal fat with a maximum stage was reported for colon and rectal cancer of T3N1.All rectal patients were evaluated by computed tomography (CT) scan and a colonoscopy. In addition, magnetic resonance imaging (MRI) was used for further evaluation of the patients with rectal cancer. All diagnoses of rectal or colonic adenocarcinoma were madePreoperative chemoradiation therapy was administered to one patient with low-rectal cancer with a preoperative stage III (T3N1 M0). Four (40%) patients underwent an anterior and a low anterior resection, two (20%) underwent a covering ileostomy and a right hemicolectomy, and one patient (10%) underwent a left hemicolectomy. Most (90%) procedures were performed laparoscopically and 10% were conducted robotically .3. Three (30%) patients were anemic, with a mean hematocrit of 34.65 ± 7.72% (range 26.7–53.4%) and a mean hemoglobin concentration of 11.38 ± 2.54 (range 8.9–17.4) g/dL. Mean preoperative urea and creatinine levels were 27.7 ± 23.62 (range 11.4–89.4) mg/dL and 1.43 ± 0.98 (range 0.59–3.94) mg/dL, respectively.Pre- and postoperative laboratory blood findings were evaluated every other day to minimize intra- and postoperative complications . The mea3) was slightly but significantly higher than the preoperative value (P = 0.032), and no severe leukocytosis or leukopenia was seen. Mean postoperative urea and creatinine levels were 18.35 ± 17.8 (range 11.4–60.7) mg/dL and 1.40 ± 0.76 (range 0.72–3.09) mg/dL, respectively.Most of the immunosuppressive medications used pre- and postoperatively were Cyclosporine or Tacrolimus combined with low dose of steroid ranging between 5 mg to 12 mg. No change in immunosuppressive medication or dosage was documented. The mean postoperative hemoglobin concentration was 10.63 ± 2.45 (range 7.6–16.1) g/dL and no patient required a blood transfusion. The mean postoperative leukocyte count  mmThe mean interval between kidney transplantation and surgery was 11.7 (range 1.3–22) years.Operative data were evaluated. The mean operating time was 192.5 ± 53.87 (range 77–263) min. Operating time was longest (263 min) for the robotic surgery. The mean operating time for laparoscopic surgery was 184.6 ± 50.74 min. The mean estimated blood loss was 30 ± 53.74 (range 0–150) mL. No conversion was required in any of the cases. We rarely found adhesions; most observed were minimal and were noted when the peritoneum was opened accidentally during the kidney transplant or another procedure. Mild adhesions do not contraindicate minimally invasive surgery or indicate an immediate conversion.No significant difference was observed between pre- and postoperative kidney function parameters, and no organ rejection was reported.The mean hospital stay was 9.7 ± 5.5 (range 5–25) days. The mean timing of the first oral intake was 3.8 ± 5.81 (range 2–7) days postoperatively. Two (20%) patients had minor postoperative complications: wound seroma and chyloperitoneum. Postoperative stages were I in 20% of the patients, II in 50% of the patients, and III in 30% of the patients .One patient underwent adjuvant chemoradiation (Xeloda (capecitabine) + radiation) and four patients underwent adjuvant chemotherapy alone  in three cases, and 5-fluorouracil + leucovorin in one case).Over a median follow-up period of 31.4 ± 21.57 (range 2–63) months, no mortality occurred. One patient showed liver metastasis 1 year postoperatively, which was treated by radiofrequency ablation and no further recurrence till the present date of our study. In six patients who were followed for a mean of 43.5 ± 9.84 (range 32–63) months, the 3-year disease-free rate was 83.3% and the 3-year overall survival rate was 100% .The risk of colorectal neoplasia is high among renal transplant recipients and is associated with the duration of immunosuppression, regardless of age . The repP = 0.031). Kasiske et al. [Kim et al.  found the et al.  also repIn contrast, Saidi et al.  found noParnaby et al.  reportedPatients on immunosuppressive medications or who have undergone organ transplantation with comorbidities have increased morbidity (stress-related complications) and mortality and a prolonged postoperative recovery period, after major open surgery, including colorectal surgery –15.Wichmann et al.  reportedTechnically, selection of the port insertion site is the most important step in a laparoscopic or robotic procedure. After the establishment of pneumoperitoneum, the kidney is moved inferolaterally to allow port placement. Although unproven, lower pneumoperitoneum pressures seem to help preserve allograft function .Our hospital is one of the leading hospitals in robotic surgery in Korea. As we reported in our results, that one case was performed by robotic method. In that case, we used a hybrid technique where the colonic mobilization was completed laparoscopically and the Da Vinci robot was used only for pelvic dissection. We found that the robotic port position of the 3rd arm should be positioned on the opposite side of the transplanted kidney because of its close proximity with the anterior superior iliac spine where the kidney is located even after pneumoperitoneum. However, any port position even in totally robotic technique could be safe as long as the ports are placed away from transplanted kidney.We found no or minimal adhesion during the procedures, which may have been related to peritoneum opening during retroperitoneal dissection in the kidney transplant procedure. Adhesions from previous surgeries, possibly related to the use of steroids, were not an issue.Only one case series of laparoscopic-assisted colectomy in three kidney transplant recipients has been published . In thatOur series was larger than that described above, and it included patients with colonic and rectal cancer. Moreover, we included patients who underwent laparoscopic and robotic surgery. In our series, the mean interval between kidney transplantation and diagnosis of colorectal cancer (11.7 years) was slightly longer. Our mean operative time was 192.5 ± 53.87 (range 77–263) min, due to the longer operative time (263 min) of the robotic procedure; the mean operative time for laparoscopic procedures was 184.6 ± 50.74 min. We observed similarly intact renal function and no rejection during the follow-up period. Two patients in our series had minor complications (wound seroma and chyloperitoneum) that were managed conservatively. The leukocyte count is normally raised after any major surgical procedure, but no severe leukocytosis or leukopenia occurred in our patients indicating infection or rejection. No change in the form or dosage of immunosuppressive medications was required before surgery, and medications were resumed postoperatively under monitoring by the transplant team.In general, these patients are more susceptible to perioperative complications. Immunosuppression can lead to a higher infection rate and surgical stress can increase immunosuppression, a phenomenon that is more pronounced following open (versus laparoscopic) surgical procedures , 14, 15.Our follow-up period (mean 31.4 ± 21.57 months) was longer than that previously reported. In addition, the mean follow-up period was 43.5 ± 9.84 months for the six patients in whom long-term outcomes were assessed. No mortality occurred; the 3-year disease-free rate was 83.3%, and the 3-year overall survival rate was 100%.In conclusion, minimally invasive surgery is feasible in kidney transplant recipients, who can benefit from fewer wound-related problems. Technical proficiency, experience, and the use of a multidisciplinary team approach including an oncologist and transplant team can result in a successful procedure and ensure the safety of the transplanted kidney. Therefore, minimally invasive colorectal procedures could be considered safe alternatives to open colorectal resection in selected kidney transplant patients.


Traveling to seek specialized care such as liver transplantation (LT) is a reality in the United States. Patient migration has been attributed to organ availability. The aims of this study were to delineate patterns of patient migration and outcomes after LT.All deceased donor LT between 2008–2013 were extracted from UNOS data. Migrated patients were defined as those patients who underwent LT at a center in a different UNOS region from the region in which they resided and traveled a distance > 100 miles.Migrated patients comprised 8.2% of 28,700 LT performed. Efflux and influx of patients were observed in all 11 UNOS regions. Regions 1, 5, 6, and 9 had a net efflux, while regions 2, 3, 4, 7, 10, and 11 had a net influx of patients. After multivariate adjustment for donor and recipient factors, graft (p = 0.68) and patient survival (p = 0.52) were similar between migrated and non-migrated patients.A significant number of patients migrated in patterns that could not be explained alone by regional variations in MELD score and wait time. Migration may be a complex interplay of factors including referral patterns, specialized services at centers of excellence and patient preference. To date, very few studies examining LT candidate migration have been published[Many patients in the United States pursue health care treatment outside of their immediate geographic area in a concept coined “destination health care”[,2. Patie”[–5. Candipublished–6. In adpublished,4. To daAfter approval from the Mayo Clinic Institutional Review Board, data were obtained and extracted from the UNOS Standard Analysis and Research file. None of the transplant donors were from a vulnerable population. All patient records and data was anonymized and de-identified prior to analysis. The study population included all deceased donor LT recipients performed in the US from June 17, 2008 to June 16, 2013. This period was chosen to encompass the 5-year time period prior to the inception of Share 35 rule, which preferentially allocated liver grafts at a regional level to patients with a MELD score of ≥35. Pediatric (age<18years), and multi-organ transplants (except simultaneous liver-kidney transplants) were excluded from this analysis. Non-US residents were also excluded from the analysis.Patients’ home region of residence and UNOS region in which they received LT were extracted using US Postal zip codes. Distances between a patients home address and transplanting centers was calculated using Google’s mapping API software. Migrated patients were defined as those patients who underwent LT at a transplant center that was in a different UNOS region from the region in which they reside and traveled greater than 100 miles. One hundred miles was chosen in order to exclude patients who were travelling to transplant centers that were in close proximity but located in a different UNOS region. A cutoff of 100 miles has previously been shown to be associated with worse survival in a study of US veterans undergoing LT. Graft st test for continuous variables and by the χ2 test or continuity correction method for categorical variables. Wilcoxon rank-sum was used for variables that did not display a normal distribution. Survival curves for patient or recurrence free survival were generated using the Kaplan-Meier method and compared by the log-rank test. All statistical tests were two-sided and differences were considered significant when p < 0.05.All statistical analyses were performed using STATA 12 . Differences between groups were analyzed using the unpaired Table 1. This included 26,345 (91.8%) patients who were transplanted in their local UNOS Region and 2355 (8.2%) patients who migrated to another UNOS Region and traveled greater than 100 miles for LT. There was no significant difference in the number of patients who migrated by year from 2008–2013 (p = 0.41). Mean travel distance from the patients’ home to their transplant center was 740.9 ± 696.8 miles (median: 478.4 miles) for patients who migrated and was 71.9 ± 149.0 (median: 31.6 miles) for those who did not migrate (p<0.001). There was no difference in recipient age between migrated (mean: 54.7 ± 10.5 years) and non-migrated patients (mean: 54.4 ± 10.3 years) (p = 0.15). Migrated patients were more likely to be male , were more likely to be identified ethnically as white  and had a lower BMI . Migrated patients were less likely to have positive serology for hepatitis C virus , were less likely to have alcohol related cirrhosis  and were less likely to have received MELD exception points for HCC . Migrated patients were more likely to have a cholestatic etiology of their liver disease . A significantly higher proportion of migrated patients were candidates for re-transplants . A smaller proportion of patients with blood group B and AB migrated compared to those that did not migrate . The proportion of patients with blood groups O and A who migrated and non-migrated was not significantly different . The proportion of patients listed at multiple transplant centers was more common in patients who migrated compared to those who did not migrate .A total of 28,700 LT were performed in the study time period. A breakdown of the UNOS regions where each of these patients initially resided and where they were ultimately transplanted can be seen in Table 2.Time on the waitlist at the transplanting center was significantly shorter for migrated patients compared to those who did not migrate . There were no significant differences in donor age between migrated and non-migrated LT recipients , or DRI of the graft . Biological MELD score at the time of LT was lower for migrated patients versus those who did not migrate , match MELD score was also lower for migrated patients in comparison to those who did not migrate . Recipient characteristics for the two study groups can be seen in Table 3. UNOS Region 3 had the highest total number of LT performed (n = 4930) while UNOS Region 6 had the least (n = 723). Regions who had a net efflux of patients included: Region 5 (n = -266), Region 9 (-178), Region 6 (n = -119) and Region 1 (n = -68). Regions who had a net absolute influx of patients included: Region 11 (n = 197), Region 10 (n = 122), Region 7 (n = 109), Region 8 (n = 92), Region 3 (n = 66), Region 2 (24) and Region 4 (n = 22). In a separate subanalysis, when transplant centers were divided into quartiles based on transplant volume and high volume centers were defined as those above the 75th percentile for transplant volume, the majority of migrated patients traveled to the high volume centers .A summary of the number of patients migrating in and out of each region can be seen in A total of 2008 (7.0%) patients were multi-listed at more than one transplant center during the study period. The proportion of multi-listed patients transplanted within each respective region was highest in UNOS Region 4 (22.9%) and lowest in UNOS Region 5 (3.7%). A subgroup analysis was performed looking only at those patients who migrated to another UNOS Region and were multi-listed: a total of 589 patients, who migrated and were multi-listed, were identified. This group accounted for 2.1% of the total number of patients transplanted in the study time period. When looking at the UNOS region from which patients migrated, the proportion of patients who migrated and were multi-listed was: Region 9 (5.3%), Region 5 (5.0%), Region 1 (4.9%), Region 6 (1.9%), Region 2 (1.6%), Region 8 (1.6%), Region 7 (1.1%), Region 4 (1%), Region 3 (1%), Region 11 (0.66%) and Region 10 (0.5%). The same cohort of patients migrated to and received their transplant in the following UNOS regions: Region 10 (4.5%), Region 3 (4.5%), Region 11 (2.7%), Region 8 (2.1%), Region 4 (1.9%), Region 6 (1.0%), Region 7 (1.0%), Region 2 (0.7%), Region 1 (0.3%), Region 5 (0.3%) and Region 9 (0.1%).. A multivariate Cox proportional Hazards model, adjusting for both donor and recipient factors, showed migrating to another region (p = 0.68) or multi-listing (p = 0.24) were not associated with graft survival. A separate multivariate Cox proportional Hazards model looking at patient survival showed migrating to another region or multi- listing were also not significant (p = 0.52) and (p = 0.06).On unadjusted analysis, there was no significant difference in graft or patient survival between migrated and non-migrated patients   that cause patients to seek LT at centers that are not in their general vicinity. We limited our analysis to the 5 years prior to implementation of the Share 35 rule in order to avoid differences in patient migration that may have arisen as a consequence of this policy. Subsequent studies could compare patient migration in the pre- and post-Share 35 eras.In conclusion, the present study provides a detailed description of patient migration and fills a gap in the overall picture of LT practice in the US. Regional variation in MELD score at LT is undoubtedly a driving force for a subset of patients to migrate. However, this study demonstrated that patient migration for LT may be a complex interplay of many factors such as physician referral patterns, insurance contracting, availability of specialized services at centers of excellence and patient preference. In addition, patient migration did not result in any difference in patient or graft survival following LT.


Abstract2 grid square occupancy across the whole island. These data were used in a study on the recent vegetation change in the island. These data include 3786 observations of 450 taxa collected in two surveys in 2007 and 2008.Amrum is a small barrier island on the north-west coast of Germany. The distribution of vascular plants was examined by surveying their 1km Amrum has been the subject of many botanical surveys and this survey continues that tradition (Amrum is a small barrier island off the coast of Schleswig-Holstein, Germany. It covers an area of about 20 kmradition .Amrum is approximately 10 km long and 3 km wide at its widest point (Fig. These data were used in a study of change in the islands flora . They arThe survey covered all vegetated areas of the island were access was permitted. In fact, this covers most of the island, however, some nesting bird colonies and private gardens are completely inaccessible.2 varies considerable so there was no set time limit for surveying a particular square. Grid squares were surveyed as intensively as considered necessary to find all but the rarest species. Aerial photographs, maps, previous surveys and local experts were all used to direct surveying to all potentially important habitats. The grid is based upon the spatial reference system EPSG:31467 - DHDN / Gauss-Kruger zone 3 (Fig. The biodiversity of each 1 kmSalix specimens where identified by R.D. Meikle.Some Amrum is one of the North Frisian Islands, Schleswig-Holstein, Germany. Its western coast faces the North Sea and the eastern coast faces the Wadden Sea Fig. .54° 36' 22.9602" and 54° 42' 44.1936" Latitude; 8° 17' 26.5308" and 8° 24' 12.6138" Longitude.The study covers all vascular plants growing in the wild. Obviously cultivated plants were excluded, though trees planted for forestry were included as these form so much of the island's habitats. Some examples of natural habitats on Amrum are illustrated Fig. .Data range: 2008 7 05 – 2008 7 20; 2007 8 17 – 2007 8 31.Creative Commons CCZeroVascular plant survey of Amrum 2007-2008http://www.gbif.org/dataset/e6fb3d46-977a-4deb-99be-e8493024feb21Survey of the whole islandDarwin Core archive43UTF-81Supplementary material 1The distribution of the vascular plants on the North Frisian Island, AmrumData type: occurrencesBrief description: A Darwin Core Archive of vascular plant occurrences from the island of Amrum, Germany recorded in 2007 and 2008File: oo_6541.zipQuentin J. Groom


A randomized multicenter phase II trial was conducted to assess the sequential treatment strategy using FOLFIRI.3 and gemcitabine alternately (Arm 2) compared to gemcitabine alone (Arm 1) in patients with metastatic non pre-treated pancreatic adenocarcinoma. The primary endpoint was the progression-free survival (PFS) rate at 6 months. It concludes that the sequential treatment strategy appears to be feasible and effective with a PFS rate of 43.5% in Arm 2 at 6 months (26.1% in Arm 1). This paper reports the results of the longitudinal analysis of the health-related quality of life (HRQoL) as a secondary endpoint of this study.HRQoL was evaluated using the EORTC QLQ-C30 at baseline and every two months until the end of the study or death. HRQoL deterioration-free survival (QFS) was defined as the time from randomization to a first significant deterioration as compared to the baseline score with no further significant improvement, or death. A propensity score was estimated comparing characteristics of partial and complete responders. Analyses were repeated with inverse probability weighting method using the propensity score. Multivariate Cox regression analyses were performed to identify independent factors influencing QFS.98 patients were included between 2007 and 2011. Adjusting on the propensity score, patients of Arm 2 presented a longer QFS of Global Health Status (Hazard Ratio: 0.52 [0.31-0.85]), emotional functioning (0.35 [0.21–0.59]) and pain (0.50 [0.31 – 0.81]) than those of Arm 1.Patients of Arm 2 presented a better HRQoL with a longer QFS than those of Arm 1. Moreover, the propensity score method allows to take into account the missing data depending on patients’ characteristics.2006-005703-34. .Eudract N°  The results of a phase II trial concerning untreated patient with metastatic Pancreatic Cancer (mPC) have shown that sequential treatment using FOLFIRI.3 and gemcitabine was effective and safe .In first line treatment, FOLFIRINOX protocol and the association of nab-paclitaxel + gemcitabine improve overall survival (OS) ,3 and rePrognosis of patients with mPC remains extremely poor. In consequence, HRQoL is a major subject of concern for these patients who are often painful and symptomatic at the time of diagnosis. Moreover, HRQoL appears to be an independent prognostic factor for OS alongside classical clinical and demographic factors . In metaHowever, HRQoL results remain poorly used to modify therapeutic strategies, due to the complexity of its longitudinal analysis and to a lack of standardization. Moreover, results should have the ability to translate findings into information that decision makers find understandable and compelling.In recent years, time to event models like time until definitive HRQoL score deterioration (TUDD) have been proposed as a modality of longitudinal HRQoL analysis in oncology, especially in metastatic setting . The TUDOne other major concern of longitudinal HRQoL studies is missing data , specifiThen it would be interesting to develop a method to use in conjunction with QFS to handle with informative missing data. Methods using the propensity score are often used in observational studies in order to reduce the bias of the absence of randomization and to allow causal inference . The proThe objective of this study was to compare longitudinal HRQoL according to treatment arm using QFS in a metastatic setting and secondary to investigate the application of the IPW method based on the propensity score in conjunction with the TUDD in order to take into account missing data depending on patients’ characteristics.https://eudract.ema.europa.eu/; N° 2006-005703-34) before the start date. The design of this study has been extensively described elsewhere  but not in Arm 1 with only 12 patients alive and free of progression resulting in a 6-month PFS rate of 26.1% [12.9–39.3].Among all randomized patients, the estimated 6 months PFS rate was 25.7% 95%CI 14.4–38.6] for Arm 1 and 44.9% [30.7–58.0] for Arm 2. The objective response rate was 10.2% [1.4–19.0] for Arm 1 and 36.7% [22.7–50.7] for Arm 2. Median OS was 8.2 months [95%CI 5.3–9.2] in Arm 1 and 11 months [7.8–13.6] in Arm 2 ), the presence of lymph node metastases (7.90 [95%CI 1.12–164.12]), a low neutrophils (2.13 [95%CI 0.64–7.25]) and platelets rate (2.77 [95%CI 0.84–9.72]) and a high hemoglobin rate (1.80 [95%CI 0.54–6.10]) were independently associated with partial responder profile but not statistically significant. The area under the ROC curve was equal to 0.76.In Arm 1  and Arm 2 (gemcitabine + FOLFIRI.3) respectively:- 18 and 17 patients experienced a QFS of GHS, among the 63 patients retained .- 19 and 17 patients experienced a QFS of physical functioning, among the 65 patients retained - 19 and 18 patients experienced a QFS of emotional functioning, among the 63 patients retained .- 18 and 17 patients experienced a QFS of fatigue, among the 65 patients retained .- 18 and 16 patients experienced a QFS of pain, among the 65 patients retained .Regarding the unweighted analysis , patientVariables retained for the Cox multivariate analysis were treatment arm (Arm 2 vs. Arm 1), number of metastatic sites (2 or more vs. 1) and an interaction effect between treatment arm and the number of metastatic sites, according to the univariate Cox regression analysis (data not shown).In the unweighted analysis, all the 95%CI contained the value of 1. Regarding the weighted analyses, the treatment arm (gemcitabine + FOLFIRI.3) and the number of metastatic sites (one site) seemed to be independently associated with longer QFS of physical functioning . The numAs for the unweighted analysis, the same trends were observed for the sensitivity unweighted analysis integrating non-responders patients see  Tables.As previously reported, patients treated with sequential chemotherapy FOLFIRI.3 + gemcitabine presented a benefit in PFS at 6 months (44.9% (30.7–58.0) vs. 25.7% 14.4–38.6)), OS (64.7%(49.5–76.4) vs. 62.8% (47.6–74.7)) and objective response rate (36.7% vs. 10.2%) [4.4–38.6)Meanwhile to the recent progress in the improvement of OS, preserving HRQoL is of paramount importance considering the symptom burden and the poor prognosis of mPC. If several Phase III trials attempted to show a clinical benefit or improvement in HRQoL, few have achieved their goals ,32. ReceIn our trial, HRQoL results support the efficacy profile of FOLFIRI.3 + Gemcitabine regimen. Patients in FOLFIRI.3 + Gemcitabine arm presented a longer QFS than those of gemcitabine alone arm whatever the HRQoL score considered in both QFS analyses even if patients in FOLFIRI.3 + Gemcitabine arm presented twice as much as those of Gemcitabine alone arm occurrence of grade 3 or 4 neutropenia. In multivariate weighted analysis, treatment with sequential FOLFIRI.3 + gemcitabine seemed to be associated with longer QFS in each HRQoL score considered including pain and fatigue score, two symptoms commonly present at time of diagnosis. It would be interested to study the impact of the occurrence of at least one grade 3–4 toxicity on the QFS.Median QFS for each domain was shorter than median PFS irrespective of the use of IPW method. It is noteworthy that survival estimates depend on the QFS definition. Contrary to our definition, all-cause death was not integrated as an event in the definition of TUDD chosen by Gourgou-Bourgade et al. . In consIf QFS is increasingly used in clinical trials, consensual methods to optimize management of missing data are still lacking ,33–35. IIn our study, in both unweighted and weighted analyses, patients in Arm 2 presented a longer QFS than patients in Arm 1. In multivariate analyses, treatment arm (gemcitabine + FOLFIRI.3) and number of metastatic sites (one site) tended to be associated with longer QFS of physical functioning in the weighted analysis. The same trends were observed for the unweighted analysis.In this way, using the IPW method of the propensity score influences the results of the multivariate analysis by underlining more significant associations. A high weight is assigned to patients with no missing data (mainly patients of Arm 1) and a low weight to partial responders (mainly patients of Arm 2). As in unweighted analysis, a longer QFS was yet observed for patients of Arm 2 as compared to those of Arm 1 for most HRQoL dimensions, the HR increased with the use of the IPW method. The use of the propensity score in conjunction with the TUDD method allowed reducing the bias due to the occurrence of missing data depending on patients’ characteristics during the follow-up. This bias cannot be totally eliminated because missing data can also depend on unobserved data. However, some logistic problems could explain the reasons for partial and non-responders because these patients were followed in the study for other endpoints. Another statistical approach to use in conjunction of the QFS method should be proposed to adequately take into account missing not at random data.Besides primary prevention procedures for limiting missing data rate, additional work on statistical methods to handle with missing data is still needed. Multiple imputations on the HRQoL scores could also be performed but this method requires a larger sample and can only retain one or two factors associated with missing data , more vaIn conclusion, analyses of QFS supports that sequential strategy with FOLFIRI.3 followed by gemcitabine in patients with untreated mPC is feasible and, despite more toxicities, delayed the HRQoL deterioration. Moreover, using the propensity score allows controlling the imbalance of informative missing data between the two arms and provides more precise estimation of the treatment effect. This sequential treatment strategy will now be compared with FOLFIRINOX in a phase III trial (French study). This phase III clinical trial will allow to confirm or not these results raised from an exploratory analysis.S1 Checklist(DOC)Click here for additional data file.S1 Authorization(DOCX)Click here for additional data file.S1 FigaArm 1: gemcitabine alone, Arm 2: gemcitabine + FOLFIRI.3.(EPS)Click here for additional data file.S1 Informed Consent(DOCX)Click here for additional data file.S1 Protocol(DOC)Click here for additional data file.S2 Protocol(DOC)Click here for additional data file.S1 Table(DOC)Click here for additional data file.S2 Table(DOC)Click here for additional data file.S3 Table(DOC)Click here for additional data file.S4 Table(DOC)Click here for additional data file.


To evaluate the frequency of fetomaternal outcome of pregnancy with Mitral stenosis admitted in Civil Hospital Karachi.It was a two years descriptive study done in the Department of Obstetrics and Gynaecology Civil Hospital Karachi. All pregnant women with a known or newly diagnosed Mitral stenosis on echocardiography were included in the study. History was taken regarding age, parity, gestational age  and complaints. Mode of delivery and Maternal mortality noted. Foetal outcome was analyzed by birth weight and Apgar score.A total of 101 patients meeting the inclusion criteria were enrolled in the study. The ages of the women ranged between 20-29 years (69%) and 81% were multigravidas. Vaginal delivery occurred in 67 (66.3%) women and 78.3% were term pregnancies. Preterm deliveries were 21.8% and 27.7% newborns were low birth weight. APGAR score <7 was found in 14.9% of neonates and 9 babies had intrauterine death. Low ejection fraction<55% was diagnosed in 20(13.9%) women and Maternal mortality was found in two cases.Heart disease in pregnancy is associated with significant morbidity, it should be carefully managed in a tertiary care hospital to obtain optimum maternal and foetal outcome. The incidence of clinically significant cardiac disease during pregnancy has not changed for decades. The most recent studies report incidence of 0.1 to 4%.6To improve care further we need to know why pregnant women are still dying, it is therefore important to identify strategies to reduce maternal deaths due to cardiac disease in pregnant women.8These patients must be managed with a multidisciplinary approach, with the collaboration of an obstetrician and cardiologist. Furthermore, this management must commence before conception, the family should be counselled about the possible risks and optimal conditions must be maintained for conception.10The aim of study is to evaluate the frequency of fetomaternal outcome of pregnancy with Mitral Stenosis. This study provides local data and describe the burden of disease thereby helping in development of a patient specific management plan.st January 2011 to 31st December 2012. One hundred and one patients admitted in Department of obstetrics and Gynaecology, Civil Hospital, Karachi were included following non probability, convenient sampling.This descriptive, case-series study was conducted in the department of obstetrics and gynaecology, Civil Hospital, Karachi from 1All women with Mitral stenosis  diagnosed on echocardiography after first trimester .All women with other medical disorders, e.g. anemia, congenital heart diseases, cardiomyopathy hypertension, asthma, diabetes mellitus, renal disease, thyroid disease, Smokers.Women admitted with Mitral stenosis were enrolled in the study. The purpose, procedure of the study was explained and informed consent was taken. History was taken regarding age, parity, complaints like breathlessness, generalized weakness, palpitations. Gestational age was calculated by ultrasonography. All patients were advised Echocardiography for diagnosis and severity of Mitral stenosis. Assessment of patient for new onset heart failure and Ejection fraction were recorded. Mode of delivery was observed. Maternal death was noted. Fetal outcome was assessed in terms of low APGAR score at five minutes, low birth weight, prematurity  and intrauterine death. This information was entered in proforma.SPSS version 10 was used for data analysis. Mean ± SD was calculated for age, parity, gestational age, low APGAR score (<7 at five minutes), low birth weight (<2.5 kg), ejection fraction. Frequency and percentages were calculated for patients with mild, moderate and severe mitral stenosis, patients who develop heart failure, patients who expired, mode of delivery, and foetal outcome like intrauterine death, low birth weight, prematurity. Stratification was done with regards to age, parity, booking status and severity of Mitral stenosis to see the effect of these on outcome.2) were included in the study. Mean ± SD age of patients was 26.3 ± 4.3 years. Majority of women 70 (69.3%) were between 20 – 29 years of age. Among 101 women, 82 (81.2%) women were multiparous, while 19 (18.8%) women were primigravida. Forty two (41.6%) women were booked and 59 (58.4%) were unbooked. Mean ±SD gestational age at birth was 36.3 ±2.8 weeks. Pre-maturity (< 37 weeks of gestation) was found in 22 (21.8%) case. Table-IA total of 101 pregnant women at 13 – 42 weeks of gestation with mitral stenosis  women followed by lower segment caesarean (LSCS) in 34 (33.7%) women. Mean ± SD birth weight of neonates was 2.6 ± 0.52 kg. Low birth weight (<2.5kg) was found in 28(27.7%) neonates. Mean ± SD APGAR score was 6.99 ± 0.9. APGAR score < 7 was found in 15 (14.9%) neonates. Intrauterine death occurred in 9 (8.9%) of cases. Maternal mortality was 1.9%. Table-IIModerate stenosis were found in 26 (25.7%) women and severe stenosis in 14 (13.9%) women. New onset of heart failure was diagnosed on echocardiography. Low ejection fraction (less than 55%) was diagnosed in 20 (13.8%) women. Table-IVProportion of low APGAR score, low birth weight and pre-maturity were high in mild mitral stenosis. Women with mild Mitral stenosis had premature babies in 12(54.5%) cases, APGAR score <7 in 8 (53.3%) cases and 14(50%) neonates had low birth weight. Frequency of intra uterine death (IUD) was high in severe mitral stenosis. Table-VManagement of pregnancy in patients with valvular heart disease (VHD) continues to pose a challenge to the clinician. Although the risk in such patients have been recognized, they have not been well defined as available information is based mostly on anecdotal reports or small series of patients without an appropriate control population.1Heart diseases are the most important non obstetrical causes of maternal deaths during pregnancy, accounting for almost 10% of maternal deaths. They complicate 1-3% of all pregnancies with congenital defects in 70-80% of the cases.Child bearing women with cardiac disease present a unique challenge to the health care provider. The physiological adaption or pregnancy predisposes cardiac patient to decompensate. Classic symptoms of heart disease mimic common symptoms of pregnancy. Detail assessment of patient throughout pregnancy may lead to initial discovery of heart disease.15In this study mild mitral stenosis was found in 60.4% women, moderate stenosis in 25.7% and severe in 13.9% of women. Vaginal delivery was the most common mode of delivery found in 66.3% women followed by lower segment caesarean section (LSCS) in 33.7% women, which is in accordance with the result of 13% in a study by Avila et al.16A study done by Hameed et al.Fetal outcome depends on the degree of maternal well being and gestational age. Cardiac patients have babies lighter by about 200gm. Mean ± SD birth weight of neonates was 2.6 ±0.52kg. Low birth weight (<2.5kg) was seen in 27.7% neonates. Mean ± SD gestational age at birth was 36.3 ± 2.8 weeks. Pre-maturity was found in 22 (21.8%) cases. A local studyMaternal mortality generally varies directly with functional classification at pregnancy onset. There were two maternal deaths comparable with the study done by Wasim T±kg. Another studyA study done by Sawhney et al.Pregnancy in our patients was associated with an increased incidence of IUGR, preterm deliveries and lower birth weight, especially in cases with moderate and severe Mitral stenosis. Hemodynamic compromise secondary to valvular stenosis and the resulting decrease in uterine blood flow are probable explanations for the high incidence of impaired intrauterine fetal growth seen in this study. The importance of prepregnancy diagnosis, counseling and contraception are essential to safely manage the planned pregnancies in cardiac patients.22Heart disease in pregnancy is associated with significant morbidity, it should be carefully managed in a tertiary care hospital to obtain optimum maternal and fetal outcome.Cardiac disease during pregnancy continues to be a major health problem, especially in developing countries. Some recommendations to reduce the fetomaternal morbidity and mortality are:Multidisciplinary approach involving a cardiologist, neonatologist and obstetricians.Raising the status of government health care facilities where less privileged women have access.Adequate training of health care of workers in the identification of symptoms and signs of cardiac disease for early detection and referral.Routine examination of the cardiovascular system in the antenatal clinic is essential for early diagnosis and appropriate management.Once identified, a pregnant woman with cardiac disease must follow secondary and tertiary levels of care by specialized units.Pre-pregnancy counselling.Particular attention need to be paid on contraception and future pregnancies.Close surveillance during pregnancy. Monitoring should continue after delivery.Adequate and timely follow up.


Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population.Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014.The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects  were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies  detected in 16.3%. Hashimoto’s thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%.This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespan. Turner syndrome (TS) is a genetic disorder characterized by total or partial absence of one sex chromosome . It is oTS is associated with several morbidities that increase with age. Although TS causes several multisystem disorders, the most common presentation is usually due to short stature and primary gonadal deficiency. Patients may present with congenital malformations such as horseshoe kidney and coarctation of the aorta. They may also develop diabetes, hypothyroidism, hypertension, hearing loss, osteoporosis and bone fractures ,5. TimelIn the present study, we aimed to define the frequency of associated problems in TS patients during childhood and the distribution of these clinical features according to karyotype and age by evaluating 842 patients with TS from 35 centers in Turkey.In this study, we retrospectively evaluated the files of 842 TS patients aged 0-18 years who were being followed in 35 different centers from different regions of Turkey between September 2013 and February 2014. The study was approved by the Ethics Committee of Gülhane Military Medical Academy. All collected data were obtained from patient hospital records; no private information was included in the study.A common case recording form (CRF) was created after literature review by four physicians  who were all experienced in TS and an expert on electronic CRF preparation (CA). The CRF covered demographic features, as well as clinical and laboratory findings of TS patients. The CRF was uploaded to the website of FAVOR Web Registry System (www.favorsci.org). Data entered in the registry were also checked for consistency by a research assistant (EY).Physicians who were conducting an outpatient clinic for TS patients were asked to register their TS patients using the paper-based study forms. Another physician in each center was asked to register each patient online using the FAVOR Registry System. The time given for patient enrollment was four months and this time period ended on January 31, 2014, after which date the collected patient record data were entered to Microsoft Excel database and subsequently transferred to SPSS for Windows statistical software for statistical analysis.The karyotype and the presence of sex determinant region of Y (SRY) for all patients were questioned. A standard 30-cell karyotype analysis from peripheral blood was made. Fluorescent in situ hybridization (FISH) was performed in case of strong suspicion of undetected mosaicism and 125/842 patients were analyzed for SRY by FISH method. Some centers screened all patients for SRY, but SRY results were not available from all centers. Birth history and presenting characteristics  were recorded. Findings on detailed questions relating to the cardiac, renal, gastrointestinal, endocrine systems, ear nose and throat, eye, skin and skeletal system, as well as psychosocial and metabolic problems that were relevant to TS were recorded by the physicians. Cardiac and renal findings were based on ultrasound examinations. Thyroid diseases were evaluated by testing for anti-thyroid peroxidase antibody, anti-thyroglobulin antibody, thyroid function tests and thyroid sonography.Karyotypes of patients were classified according to numerical, structural and both numerical and structural abnormalities by a geneticist (DG). Patients with a body mass index (BMI) between 85-95 percent were defined as overweight and patients with a BMI over 95 percent as obese . DyslipiStatistical analyses were performed using SPSS for Windows V. 22.0 statistical software. Frequencies and percentages represented the descriptive statistics for categorical variables and mean ± standard deviation values were used for continuous variables. Ratios were compared using chi-square test and mean values were compared using t-test. A p-value less than 0.05 was considered as statistically significant.A total of 842 patients with TS were registered. The distribution of patients according to karyotype analysis was as follows: 45,X , 45,X/46,XX , 46,X,i(Xq)  and 45,X/46,X,i(Xq)  . The numSRY analysis was performed in 106 patients. Five of the patients  and another with 45,X/46,X(Xp) were found to be positive for SRY among these 106 patients who were not detected to have a Y chromosome material by using standard methodology.The mean gestational age, birth weight and height of the patients were 39±2 weeks, 3000±580 g and 48.0±2.5 cm, respectively. The mean age of presentation to clinics was 10.2±4.4 years for the whole group. It was 10.1±4.8 years for patients with 45,X karyotype and 10.3±4.0 years for the rest of the karyotypes, p=0.391). Age at diagnosis was between the ages 1 and 12 years in 57.1% of the patients and older than 12 years in 37.2%. A histogram according to age at diagnosis is given in The most frequent complaints at presentation were short stature in 708 (84.1%) patients, delayed puberty in 130 (15.4%) patients and edema in 37 (4.4%). Other presenting complaints in 128 (15.2%) patients were dysmorphism, congenital heart diseases and antenatal diagnosis. Mean ages of presentation for short stature and delayed puberty were 10.0±3.3 years and 16.4±2.6 years, respectively.The number of patients who were investigated for associated problems and frequencies of pathologies detected in the registered 842 TS patients are presented below.Cardiac evaluation was performed by transthoracic echocardiography in 719 patients. Cardiovascular pathologies were detected in 180 (25%). Bicuspid aortic valve , coarctation of the aorta  and aortic stenosis  were the most frequently detected abnormalities . SeventeA total 117 out of 714 (16.3%) patients had renal anomalies detected on ultrasound screening. The most frequent ones were horseshoe kidney (9.0%) followed by double collector duct system (2.7%) and rotation anomalies (1.3%). Other encountered anomalies  are listed in Findings indicative of Hashimoto’s or Graves diseases were evaluated in 792 patients by testing for anti-thyroid peroxidase antibody, anti-thyroglobulin antibody, free thyroxine (T4), thyroid stimulating hormone (TSH) and/or TSH receptor antibodies and/or thyroid sonography. 74 patients were found to have hypothyroidism and 14 patients subclinical hypothyroidism with high TSH but normal free T4 levels. Thyroid autoantibodies were positive in 82 out of 792 (10.4%) patients of which 42 (51.2%) had hypothyroidism. 74% of the patients with positive thyroid autoantibody were older than 10 years, 24% of them were between 5-10 years and 2% were below 5 years of age. Only 3 patients had Graves disease. Thyroid autoimmunity was more common in patients with isochromosome karyotype (16.7%) and its frequency was significantly higher than that of other karyotype groups (9.2%) (p=0.008). No difference was observed among karyotypes with regard to hypothyroidism.Gastrointestinal abnormalities were evaluated in 698 patients by testing for liver function tests and celiac disease screening . Endoscopy, gastroscopy, colonoscopy and biopsy were performed in suspected cases. Gastrointestinal abnormalities were detected in 62 patients (8.9%). Transaminases were elevated in 24 patients and 9 patients had hepatosteatosis. Thirty-two patients were positive for celiac antibodies. The diagnosis of celiac disease had been confirmed by endoscopy in 18 patients. The most frequent karyotypes among 9 patients with hepatosteatosis was isochromosome X (p=0.008) and structural abnormalities (p=0.005).Evaluation for ear, nose and throat problems showed pathology in 122 out of 539 (22.6%) TS patients. Recurrent otitis media was the most common finding with 77 patients (14.3%), followed by hearing loss in 54 (10.0%) patients of whom 44 had conductive and 10 had sensory-neural type hearing loss. We did not find any correlation between recurrent otitis media and conductive hearing loss. Nineteen patients had undergone tympanostomia. Ear problem frequencies did not differ among various karyotypes.Although we do not know the number of patients who had been evaluated, ophthalmologic problems were reported to be detected in 74 patients, most of which were strabismus encountered in 41, myopia in 16 and ptosis in 8 patients.Dermatological problems were detected in 159 out of 729 (21.8%) patients. The most prevalent dermatologic problem was presence of nevi, observed in 114 (15.6%) patients. Psoriasis, vitiligo, alopecia and keloid were other reported dermatological problems. A statistically significant increase was detected in the frequency of nevus by age (p=0.001). The frequency of nevi was 21.8% in patients older than 10 years, 11.6% in those between 5-10 years and 4.8% in those under 5 years of age. Frequency of dermatological problems did not vary among different karyotype groups.Orthopedic evaluation by an orthopedist and/or DEXA measurement was made in 442 patients and 122 (27.6%) were found to have at least one problem. Osteoporosis and osteopenia were the most common findings in 63 (15.3%) and 49 (11.1%) patients, respectively. Scoliosis and hip dislocation were some other reported pathologies.Two hundred and ninety-one patients were assessed for psychosocial problems by pediatric and adolescent psychiatrists and/or were reported to have undergone such an assessment in their school files. The most common problems were learning difficulty (16.1%) as well as vague mental (13.7%) and emotional (6.9%) problems .Metabolic evaluation was done in 727 patients; 69 (9.5%) of these were obese and 40 (5.5%) were overweight. Insulin resistance (p=0.042) and glucose intolerance (p=0.003) were more common in patients with isochromosome X, but there was no association with obesity. Only 3 patients had type 2 diabetes and 1 patient had type 1 diabetes. The metabolic test results of TS patients of normal weight and those of overweight or obese TS patients are presented in In this study, we reviewed the presenting complaints, clinical characteristics, associated disorders and distribution of these according to karyotype analysis in 842 patients with TS from 35 centers in Turkey.TS patients mostly present with X chromosome monosomy, followed by mosaic pattern. The most common forms of mosaicism are reported as 45,X/46,XX and 45,X/46,X,i(Xq) and the most commonly reported X chromosome structural abnormality is isochromosome Xq ,2,3. In Identification of Y chromosome material in females with TS is important because of the risk of gonadoblastoma. Mosaicism for a cell line with a normal or abnormal Y chromosome is identified in 6% to 11% of patients with TS with standard cytogenetic techniques . Occult The percentage of patients with Y chromosome mosaicism (by molecular or standard cytogenetic techniques) was 8%; of these, 12% had gonadoblastoma. Detection of occult Y mosaicism in 45,X subjects using interphase FISH with a probe for the Y centromere (DYZ3) has been reported to range from 0% to 4% ,15. In oThe diagnosis of TS is usually delayed. In up to 10% of patients, diagnosis may be delayed until adulthood ,4. In 70TS is associated with a wide range of abnormalities affecting nearly every organ system. Congenital cardiovascular defects constitute the most important life-threatening pathology in these patients. It has been reported that the 50% of adult patients and 30% of pediatric patients with TS present with cardiovascular abnormalities ,17. In oIn studies with large number of patients, it was also found that cardiac malformations were more prevalent among patients with 45,X than among patients with X mosaicism and X chromosome structural abnormalities. Similarly, coarctation of the aorta predominates in patients with the karyotype of 45,X ,25,26,27Hypertension has been reported in 7-17% of children and 24-40% of adults with TS ,29,30,31Renal pathologies have been reported to be of an approximate frequency of 30% in TS patients, a frequency which is nine times greater compared to the normal population ,32,33,34TS patients have an increased risk of thyroid diseases  . In the Elevated liver enzymes and increased risk of cirrhosis have been reported in patients with TS . ImprovePatients with TS have a 2-10 fold increased risk of developing inflammatory bowel disease (3%) and a 11-fold increased risk of developing (2.2-8.1%) celiac disease as compared to the normal population . Inflammatory bowel disease was not detected in this present study. Biopsy-proven celiac disease was detected in 18 (2.5%) and celiac antibody positivity in 32 (4.5%) patients. Prevalence of celiac disease in our cohort was higher than in healthy Turkish school children which have a reported prevalence of 0.47% . No karyCraniofacial malformations that cause Eustachian tubes dysfunction may result in recurrent otitis media and consequent hearing problems in children with TS. Hearing problems may be seen up to 30% in childhood and up to 90% in adulthood in patients with TS ,47. CondOphthalmologic anomalies can be observed in about 63% of patients with TS . StrabisFemales with TS are prone to some skin pathologies such as pigmented nevi, psoriasis, alopecia areata and keloid formation after surgical interventions . PigmentOrthopedic evaluation in TS patients is of importance starting from infancy as they may have a high risk of congenital hip dislocation. In adolescence, the risk for developing scoliosis is as high as 10% ,56. In oEstrogen deficiency in patients with TS increases the risk of osteoporosis. Bone mass reduction has been reported in 25% of women with TS . OsteopoTS patients generally have normal intelligence except for mosaic karyotype with ring X chromosome. However, they have impaired non-verbal skills and low arithmetic skills. In our study, 291 patients were assessed for psychosocial problems and 39.1% were found to have psychosocial problems. Learning difficulties at school, as well as mental and emotional disorders (diagnosed by pediatric psychiatrists) were the most commonly encountered problems. These findings could be related to increased awareness of these problems as well as to inadequate adjustment to social environment. Only 11 out of 36 patients with ring chromosomes had been evaluated for psychological disorders, but there appeared to be no difference between patients with ring chromosomes and patients with other karyotypes regarding mental problems. As expected, emotional and learning problems increased with age (p=0.02), while no age difference was seen regarding mental disorders.TS girls exhibit more metabolic risk factors and reduced beta cell function compared to age- and BMI-standard deviation score-matched girls . Waist cType 2 diabetes mellitus is reported to be more common in TS. Impaired glucose tolerance is seen at early ages and although obesity is a common problem in these patients, is not associated with either karyotype or BMI ,59,60,61The present study provides data on the demographic characteristics and frequency of associated problems in TS during childhood, based on the experience of Pediatric Endocrinology centers in Turkey. The findings indicate that some of the related problems are not being thoroughly searched in all patients. In those with complete evaluation, frequency of associated problems and their relationship with the karyotype groups are similar to that reported for other populations.


In 2013, Intensive Care medicine received 1516 manuscripts, with a global acceptance rate of 20.7%. Among the full length articles , 1093 were original articles and 10.07% were accepted.This study is part of the quality control of the ICM editorial's line. Rejected papers were tracked to know in which journal and after which time these were finally accepted.not published;published in the same impact factor journal ( ± 0.5);published in higher impact factor journal orpublished in lower impact factor journals.On February 2015, a Pubmed search was performed to identify journals and publication dates for original articles rejected by ICM in 2013. Articles were considered as “published on another journal” if they met the following criteria: similar title, same first author, similar abstract, and publication year ≥ 2013. Articles were classified in 4 categories:There was no statistical correlation between submitting country and group categories. Among the 983 original articles analyzed, 485 (49.3%) were published in other Journals, with a mean ( ± SD) time to publication of 6,9 ± 3,02 months after ICM's rejection. All but 17 articles that were published elsewhere were rejected without review. 19 (4%) articles were published in journals with same IF, 14 (3%) in journals with higher IF and 440 (91%) in journals with lower IF. Twelve articles initially rejected by ICMwere finally published in ICM as letters to the editor.Table Thirteen of the rejected manuscripts (2.6%) received more than 5 citations from January 2014 to January 2015. of these, 8 were classified in the lower IF category, 2 in the same IF, 2 in ICM, and only 1 in the higher IF category. Conversely, 80 articles among 110 published by ICM during 2013 (72.7%) received more than 5 citations in the same period. Sensitivity and specificity for an article to receive more than 5 citations if accepted by ICM editorial staff was respectively 85.11% and 81.71%.About a half of ICM rejected articles were published on other journals, mostly with lower IFs. Only a very small proportion of rejected articles received a number of citations higher than ICM's IF, and it relates with the interval needed for the first decision.


Hepevirus, in the family of Hepeviridae. In this study, 46 (5.43%) out of the 847 serum samples from sika deer (Cervus nippon) were detected as seropositive with hepatitis E virus (HEV) by enzyme linked immunosorbent assay (ELISA). These samples were collected from Inner Mongolia and Jilin and Heilongjiang provinces in China, between October 2012 and October 2013. Seroprevalence of HEV infection in male and female deer was 4.82% and 6.52%, respectively. HEV seroprevalence in sika deer from different geographical locations varied from 3.13% to 6.73%. There was no significant difference in HEV seroprevalence between sika deer collected in autumn (5.65%) and winter (4.85%). This is the first report of HEV seroprevalence in sika deer in China, which will provide foundation information for estimating the effectiveness of future measures to control HEV infection in sika deer in China and assessing the potential risk of humans infected with HEV after consumption of undercooked or raw meat from infected sika deer.Hepatitis E virus (HEV), a single stranded RNA, nonenveloped virus, belongs to the genus  Hepevirus, in the family of Hepeviridae [Viral hepatitis is a global health problem , especiaeviridae –6. Previeviridae . HEV infeviridae –10.Hepatitis E was first recognized in India in 1978 . Avian HIn view of such serious situation, a large number of investigations about HEV have been carried out worldwide –27. In CThis study was approved by the Animal Ethics Committee of Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences . The sika deer, from which blood was collected, were handled in accordance with good animal practices required by the Animal Ethics Procedures and Guidelines of the People's Republic of China.The samples in this study were collected from 4 cities, Northern China . ChangchAll the sika deer blood samples  were randomly collected from the 4 cities, Northern China, between October 2012 and October 2013. All the sika deer were bred in the semifree range system. Samples were transported to the laboratory in the College of Animal Science and Technology, Jilin Agriculture University, Jilin province, China. They were kept at 37°C for 2 h and then at 4°C for 1 h, and then centrifugation was carried out at 1,000 ×g for 10 min, and the serum was separated and kept at −20°C until further analysis. Information of sika deer about seasons and geographic origin of sampling, gender, and age was recorded.Circulating antibodies (CAb) against HEV were tested by the species-independent double-antigen sandwich (das) ELISA using a commercially available kit  according to the manufacturer's instructions . PositivP < 0.05. Odds ratios (OR) and their 95% confidence interval (95% CI) were provided in this study.The differences of seroprevalence of HEV infection in sika deer from different locations, gender, and seasons were analyzed statistically using SAS software  . ResultsP > 0.05). HEV seroprevalence in sika deer from different geographical locations varied from 3.13% (95% CI 0.43–5.82) to 6.73% (95% CI 3.33–10.14), but the difference was not statistically significant among the different regions (P > 0.05). Sika deer collected in winter  had a slightly lower HEV seroprevalence compared to sika deer collected in autumn , and the difference was not significant statistically.A total of 46  3.91–6.96) out of 847 sika deer were detected as seropositive of HEV by ELISA . SeropreCervus elaphus) in Spain (10.4%) [There are many reports showing that HEV could infect deer all over the world . In the  (10.4%)  and Yezo (10.4%)  by ELISA (10.4%)  and Neth (10.4%)  and roe  (10.4%)  by RT-PC (10.4%)  and wild (10.4%)  and USA  (10.4%)  by ELISA (10.4%)  and West (10.4%)  (Table 2P = 0.36)  . ClimateP = 0.65) , but the difference was not statistically significant ( = 0.65) . This maSika deer are popular in China, and they are famous for medicinal value. Velvet antlers, blood, and meat are the main products from sika deer. Deer meat especially was widely recognized by most people with the improvement of living standards in Northern China. A study has shown that HEV could be transmitted from deer to humans , so sikaThe present investigation suggests the existence of HEV infection in sika deer, Northern China. The result may provide fundamental information for estimating the effectiveness of future measure to control HEV infection in sika deer in China and assessing the potential risk of humans infected by HEV.