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Winerdal M.E.,Unit of Clinical Allergy Research | Marits P.,Unit of Clinical Allergy Research | Winerdal M.,Astrid Lindgren Childrens Hospital | Hasan M.,Karolinska University Hospital | And 4 more authors.
BJU International

What's known on the subject? and What does the study add? Sentinel node detection in renal cell carcinoma (RCC) is a completely new field. This method of nodal detection can be utilized as a starting point for adoptive immunotherapy, only previously described in colon cancer and in advanced urothelial cancer of the urinary bladder. The study adds a description of available methods and techniques for sentinel node detection in RCC. OBJECTIVE • To investigate the possible impact of FOXP3 expression in T-cells, as well as in tumour cells, on long-term survival in patients with urinary bladder cancer (UBC) invading muscle. PATIENTS AND METHODS • In a retrospective study, tumour specimens from 37 patients cystectomized for T1-T4 UBC during 1999-2002 at the Karolinska University Hospital were examined by immunohistochemistry for tumour expression and/or infiltration of immune cells expressing FOXP3 as well as CD3. • The results obtained were correlated with clinicopathological parameters, where the primary and secondary outcomes investigated were overall survival and progression-free survival, respectively. RESULTS • Infiltration of CD3 + and FOXP3 + lymphocytes (≥3 cells per high-power field) were both correlated with better survival, and this relationship persisted throughout the whole study period (all P < 0.05). • Patients with FOXP3 + tumour cells had decreased long-term survival compared to those patients with FOXP3 - tumours (P < 0.05). • Despite a limited amount of patient material, the results of the present study indicate that FOXP3 expression, in both lymphocytes and tumour cells, is an important prognostic factor in UBC. CONCLUSIONS • FOXP3 expression in UBC cells is associated with decreased long-term survival and thus may be a novel negative prognostic factor in UBC invading muscle. • By contrast, the presence of FOXP3 + tumour-infiltrating lymphocytes was correlated with a positive prognosis. Because FOXP3 is up-regulated upon activation in human T-cells, FOXP3 may serve more as an activation marker than as a regulatory T-cell indicator in this case. • These results support the need for larger prospective studies aiming to confirm the results obtained and to examine the underlying mechanisms in detail. © 2010 BJU INTERNATIONAL. Source

Holzgraefe B.,Karolinska University Hospital | Broome M.,Karolinska University Hospital | Kalzen H.,Karolinska University Hospital | Konrad D.,Karolinska University Hospital | And 2 more authors.
Minerva Anestesiologica

Background. Severe respiratory failure related to infection with the pandemic influenza A/H1N1 2009 virus is uncommon but possibly life-threatening. If, in spite of maximal conventional critical care, the patient's condition deteriorates, extracorporeal membrane oxygenation (ECMO) may be a life-saving procedure. Methods. An observational study approved by the local ethics committee was carried out. Data from all patients treated with ECMO at the ECMO Center Karolinska for influenza A/H1N1 2009-related severe respiratory failure were analyzed. The main outcome measure was survival three months after discharge from our department. Results. Between July 2009 and January 2010, 13 patients with H1N1 2009 respiratory failure were treated with ECMO. Twelve patients were cannulated for veno-venous ECMO at the referring hospital and transported to Stockholm. One patient was cannulated in our hospital for veno-arterial support. The median ratio of the arterial partial oxygen pressure to the fraction of inspired oxygen (P/F ratio: PaO2 /FiO2) before cannulation was 52.5 (interquartile range 38-60). Four patients were converted from veno-venous to veno-arterial ECMO because of right heart failure (three) or life-threatening cardiac arrhythmias (one). The median maximum oxygen consumption via ECMO was 251 ml/min (187-281 ml/min). Twelve patients were still alive three months after discharge; one patient died four days after discharge due to intracranial hemorrhage. Conclusion. Patients treated with veno-venous or veno-arterial ECMO for H1N1 2009-related respiratory failure may have a favorable outcome. Contributing factors may include the possibility of transport on ECMO, conversion from veno-venous (v-v) or veno-arterial (v-a) ECMO if necessary, high-flow ECMO to meet oxygen requirements and active surgery when needed. Source

Hertting O.,Astrid Lindgren Childrens Hospital | Shingadia D.,Great Ormond Street Hospital
Journal of Infection

Although childhood tuberculosis has declined dramatically in the UK over the last century, it is now increasing again and globally childhood tuberculosis still accounts for a significant proportion of the tuberculosis disease burden. Children may present with non-specific symptoms, and because of the paucibacillary nature of disease and the difficulty of producing sputum samples, tuberculosis in children is often difficult to diagnose. Apart from the traditional diagnostic methods, like chest X-ray, tuberculin skin testing and mycobacterial staining or culture, new diagnostic strategies have been developed. In particular, immune-based diagnostics, such as interferon-gamma release assays, have now been introduced for clinical use. However these tests do not offer substantial improvements in sensitivity over tuberculin skin testing for the diagnosis of active disease. Further research is needed to develop better diagnostic tests for tuberculosis in children. © 2013 The British Infection Association. Source

Jakuskiene R.,Lithuanian University of Health Sciences | Vollmer B.,Karolinska Institutet | Saferis V.,Lithuanian University of Health Sciences | Daugeliene D.,Astrid Lindgren Childrens Hospital
European Journal of Pediatrics

The objectives of the study are to investigate gestational age-specific mortality and neonatal outcomes in preterm infants admitted to a tertiary center in Lithuania, and to make comparison with tertiary centers in western countries. Three hundred thirty-eight newborns born at ≤32 weeks of gestation and with birth weight ≤1,500 g between 1 January 2003 and 31 December 2005, admitted to the neonatal intensive care unit at Kaunas Medical University Hospital, were prospectively investigated. Mortality and associations between maternal, perinatal, and neonatal variables and short-term outcomes were examined for two gestational age (GA) groups (group I, extremely preterm, 22-27 weeks GA; group II, very preterm, 28-32 weeks GA). Mortality in group I was 53.5% and 2.9% in group II. GA <28 weeks, Apgar score <5 at 5 min, and birth weight <1,000 g posed the highest risk for death. Overall, 78.2% of the surviving infants were discharged from hospital without adverse short-term outcomes. The incidence of bronchopulmonary dysplasia (BPD) was 6.3%, of retinopathy of prematurity (ROP) requiring treatment 4.2%, of intraventricular hemorrhage (IVH) III-IV 10.9%, and for cystic periventricular leukomalacia (cPVL) 8.0%. In conclusion, a decade after introduction of perinatal programs, mortality in the very preterm group is similar to those reported from cohorts in western countries. In the extremely preterm group, however, mortality is still higher. Neonatal outcomes such as ROP are now similar, and BPD is lower to those in other cohorts, whereas the incidence of brain lesions is still higher. We speculate that differences in outcomes between studies may be explained by differences in resources, definitions, and treatment routines. © 2011 Springer-Verlag. Source

Simard J.F.,Karolinska Institutet | Simard J.F.,Karolinska University Hospital | Neovius M.,Karolinska Institutet | Hagelberg S.,Astrid Lindgren Childrens Hospital | And 3 more authors.
Arthritis Care and Research

Objective: Reports of therapy-related adverse events suggest an elevated rate of malignancy in patients with juvenile idiopathic arthritis (JIA) treated with biologic therapies. However, the scarcity of data on the underlying risk of malignancy in JIA hampers interpretation of these signals. Therefore, the aim of this study was to determine the risk of cancer in patients with JIA as compared with that in the general population. Methods Through linkage with a national database, the Swedish Patient Register (comprising inpatient discharges in 1969-2007 and specialist outpatient visits in 2001-2007 in Sweden), a national JIA cohort (n = 9,027) was identified, and each JIA case was matched with 5 general population comparators. Using data from the Swedish Cancer, Census, Death, and Biologics Registers, the occurrence of cancer, vital status, and start of a biologic therapy were identified. The relative risk (RR) of first occurrence of a primary cancer in patients who had not been treated with biologics (biologics-naive patients with JIA) was estimated using Poisson regression, stratified a priori by year of earliest identification of JIA (before 1987 versus 1987 and thereafter). In sensitivity analyses, the data were followed up to 1999, when biologics first became available. Results In this biologics-naive JIA cohort, 60 malignancies were observed during 131,144 person-years of followup, compared with 266 cancers observed during 661,758 person-years in the general population comparator (0.46 cases/1,000 person-years versus 0.40 cases/1,000 person-years; RR 1.1, 95% confidence interval [95% CI] 0.9-1.5). Patients with JIA identified before 1987 were not at increased risk of cancer, whereas JIA identified in 1987 and thereafter was significantly associated with incident lymphoproliferative malignancies (RR 4.2, 95% CI 1.7-10.7) and cancers overall (RR 2.3, 95% CI 1.2-4.4). Sensitivity analyses did not reveal any ready explanation for this heterogeneity. Conclusion Although absolute risks were low, an elevated risk of malignancy was observed among biologics-naive patients in whom the diagnosis of JIA was made in the past 20 years, which may have implications for the interpretation of cancer signals in patients with JIA treated with newer therapies. Copyright © 2010 by the American College of Rheumatology. Source

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