Anthrax outbreak in a Swedish beef cattle herd - 1st case in 27 years: Case report

After 27 years with no detected cases, an outbreak of anthrax occurred in a beef cattle herd in the south of Sweden. The outbreak was unusual as it occurred in winter, in animals not exposed to meat-and-bone meal, in a non-endemic country

Patterns of endogenous steroids in apathetic refugee children are compatible with long-term stress

BACKGROUND During the last few years, a number of children of asylum applicants in Sweden developed an apathetic or unconscious state. The syndrome was perceived as new, and various explanations were advanced such as; factitious disorder, intoxication, or stress. Considering a potential association between traumatic stress and regulation of steroids biosynthesis, this study explored whether changes in concentrations of endogenous steroids were associated with the above syndrome. METHODS Eleven children were recruited in the study. Concentrations of steroids in blood samples were determined using high sensitivity liquid chromatography tandem mass spectrometry methods. Symptoms were assessed with a clinical rating scale developed for the study. Steroid concentrations were measured at the entry into study and after recovery; and concentrations were evaluated for the association with the symptoms in apathetic children. RESULTS  Cortisol and cortisone concentrations at baseline were negatively associated with duration of the symptoms from entry into the study to clinical recovery. Concentrations of pregnanes (pregnenolone, 17-OH-pregnenolone, and dehydroepiandrosterone) and 17-OH-progesterone were increased in the symptomatic state and decreased after the recovery. CONCLUSIONS  Pattern of low cortisol concentrations found in apathetic children is consistent with long-term stress. An increase of upstream steroid metabolites such as pregnanes and 17-OH-progesterone was found to be associated with the symptomatic state

Patterns of endogenous steroids in apathetic refugee children are compatible with long-term stress

BACKGROUND During the last few years, a number of children of asylum applicants in Sweden developed an apathetic or unconscious state. The syndrome was perceived as new, and various explanations were advanced such as; factitious disorder, intoxication, or stress. Considering a potential association between traumatic stress and regulation of steroids biosynthesis, this study explored whether changes in concentrations of endogenous steroids were associated with the above syndrome. METHODS Eleven children were recruited in the study. Concentrations of steroids in blood samples were determined using high sensitivity liquid chromatography tandem mass spectrometry methods. Symptoms were assessed with a clinical rating scale developed for the study. Steroid concentrations were measured at the entry into study and after recovery; and concentrations were evaluated for the association with the symptoms in apathetic children. RESULTS  Cortisol and cortisone concentrations at baseline were negatively associated with duration of the symptoms from entry into the study to clinical recovery. Concentrations of pregnanes (pregnenolone, 17-OH-pregnenolone, and dehydroepiandrosterone) and 17-OH-progesterone were increased in the symptomatic state and decreased after the recovery. CONCLUSIONS  Pattern of low cortisol concentrations found in apathetic children is consistent with long-term stress. An increase of upstream steroid metabolites such as pregnanes and 17-OH-progesterone was found to be associated with the symptomatic state

Low response rate to ATG-based immunosuppressive therapy in very severe aplastic anaemia - A Swedish nationwide cohort study

Objectives: Antithymocyte globulin (ATG)-based immunosuppression remains a cornerstone in aplastic anaemia (AA) treatment. However, most ATG studies are not population-based and knowledge about real-world results concerning response and outcome could offer important information for treating physicians. Methods: We have recently performed a nationwide retrospective cohort study on all AA patients diagnosed in Sweden in 2000-2011 and now present treatment and outcome data on patients receiving first-line ATG. In total, 158 patients showed a 47.0% response rate which was similar in all age groups (range 41.5%-51.7%) with no difference regarding ATG formulation. The response was significantly associated with severity grade-especially at time of treatment initiation: very severe (VSAA) 22.7%; severe (SAA) 54.5% (P < .001); and non-severe 88.5% (P < .001). A logistic regression-based predictive model indicated that VSAA patients with an absolute reticulocyte count <25 × 109/L had only a 19% probability of response. In a multivariable analysis, age and VSAA at the time of treatment were the independent factors for inferior survival. Conclusions: Real-world VSAA patients respond poorly to ATG which indicates the need for a different treatment approach. Our findings suggest that age alone should not be a discriminating factor for administering ATG treatment

High Graft-versus-Host Disease-Free, Relapse/Rejection-Free Survival and Similar Outcome of Related and Unrelated Allogeneic Stem Cell Transplantation for Aplastic Anemia : A Nationwide Swedish Cohort Study

Allogeneic stem cell transplantation (SCT) as primary treatment for aplastic anemia (AA) is being increasingly used. Yet, age, stem cell source, and donor type are important outcome factors. We have recently performed a nationwide cohort study of all patients with AA in Sweden diagnosed from 2000 to 2011 and now present outcome data on SCT patients. In total, 68 patients underwent SCT, and 63% of them had failed immunosuppressive therapy. We found that, with a median follow-up of 109 months (range, 35 to 192 months), 5-year overall survival (OS) for all patients was 86.8%, whereas graft-versus-host disease-free, relapse/rejection-free survival (GRFS) at 5 years was 69.1%. There was no survival impact regarding the donor type or stem cell source. Patients aged ≥40 years had a higher transplant-related mortality (29.4% versus 7.8%; P = .023), which translated into a lower 5-year OS: 70.6% versus 92.2% (P = .022) and a trend of lower GRFS (52.9% versus 74.5%; P = .069). In conclusion, we found in this real-world setting that both OS and GRFS were high, but SCT for patients with AA aged ≥40 years is problematic, and clinical trials addressing this issue are warranted

Incidence and outcome of acquired aplastic anemia : real-world data from patients diagnosed in Sweden from 2000-2011

A plastic anemia is a rare life-threatening disease. However, since the introduction of immunosuppressive therapy and allogeneic stem cell transplantation, the outcome has improved considerably, and the 5-year survival is reported to be 70-80% in selected patient cohorts. Yet, contemporary population-based data on incidence and survival are lacking. We performed a national retrospective study to determine the incidence, treatment, and survival of patients with aplastic anemia diagnosed in Sweden from 2000-2011. Patients were included via the National Patient Registry, and diagnosed according to the Camitta criteria. In total, 257 confirmed cases were identified, with an overall incidence of 2.35 (95% CI: 2.06-2.64) cases per million inhabitants per year. Median age was 60 years (range: 2-92), and median follow up was 76 (0-193) months. Primary treatments included immunosuppressive therapy (63%), allogenic stem cell transplantation (10%), or single-agent cyclosporine/no specific therapy (27%). The 5-year survival was 90.7% in patients aged 0-18 years, 90.5% in patients aged 19-39 years, 70.7% in patients aged 40-59 years, and 38.1% in patients aged &gt;= 60 years. Multivariate analysis showed that age (both 40-59 and &gt;= 60 age groups), very severe aplastic anemia and single-agent cyclosporine/no specific therapy were independent risk factors for inferior survival. In conclusion, younger aplastic anemia patients experience a very good long-term survival, while that of patients &gt;= 60 years in particular remains poor. Apparently, the challenge today is to improve the management of older aplastic anemia patients, and prospective studies to address this medical need are warranted

Cancer incidence in healthy Swedish peripheral blood stem cell donors

Granulocyte colony-stimulating factor (G-CSF) has been used for over 20 years to obtain peripheral blood stem cells from healthy donors for allogeneic stem cell transplantation. Concerns have been raised about a potentially increased cancer incidence in donors after donation, especially regarding haematological malignancies. In a prospective Swedish national cohort study, we studied the cancer incidence after donation in 1082 Swedish peripheral blood stem cell donors, donating between 1998 and 2014. The primary objective was to evaluate if the cancer incidence increased for donors treated with G-CSF. With a median follow-up time of 9.8 years, the incidence of haematological malignancies was 0.85 cases per 1000 person-years, and did not significantly differ from the incidence in age-, sex- and residence-matched population controls (hazard ratio 1.70, 95% confidence interval (CI) 0.79-3.64, p value 0.17), bone marrow donors or non-donating siblings. The total cancer incidence for peripheral blood stem cell donors was 6.0 cases per 1000 person-years, equal to the incidence in matched population controls (hazard ratio 1.03, 95% CI 0.78-1.36, p value 0.85), bone marrow donors or non-donating siblings. In this study of healthy peripheral blood stem cell donors, the cancer incidence was not increased after treatment with G-CSF

Doxorubicin-provoked increase of mitotic activity and concomitant drain of G0-pool in therapy-resistant BE(2)-C neuroblastoma.

In this study chemotherapy response in neuroblastoma (NB) was assessed for the first time in a transplantation model comprising non-malignant human embryonic microenvironment of pluripotent stem cell teratoma (PSCT) derived from diploid bona fide hESC. Two NB cell lines with known high-risk phenotypes; the multi-resistant BE(2)-C and the drug sensitive IMR-32, were transplanted to the PSCT model and the tumour growth was exposed to single or repeated treatments with doxorubicin, and thereafter evaluated for cell death, apoptosis, and proliferation. Dose dependent cytotoxic effects were observed, this way corroborating the experimental platform for this type of analysis. Notably, analysis of doxorubicin-resilient BE(2)-C growth in the PSCT model revealed an unexpected 1,5-fold increase in Ki67-index (p3-fold increase in active cell cycle (i.e. cells positive staining for PH3 together with incorporation of EdU) (p<0.01). Considering the clinical challenge for treating high-risk NB, the discovery of a therapy-provoked growth-stimulating effect in the multi-resistant and p53-mutated BE(2)-C cell line, but not in the drug-sensitive p53wt IMR-32 cell line, warrants further studies concerning generality and clinical significance of this new observation