These guidelines for the management of patients up to 18 years with Langerhans cell histiocytosis (LCH) have been set up by a group of experts involved in the Euro Histio Net project who participated in national or international studies and in peer reviewed publications. Existing guidelines were reviewed and changed where new evidence was available in the literature up to 2012. Data and publications have been ranked according to evidence based medicine and when there was a lack of published data, consensus between experts was sought. Guidelines for diagnosis, initial clinical work-up, and treatment and long-term follow-up of LCH patients are presented.
Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scant. Exposure to cadmium (Cd), a ubiquitous metal associated with well-established toxic and carcinogenic properties, has been hypothesized to one putative cause of PC. Hence, we analyzed recently published observational studies, meta-analyses, and experimental animal and in vitro studies with the aim of summarizing the evidence of Cd involvement in PC development and describing the possible mechanisms. Consolidation of epidemiological data on PC and exposure to Cd indicated a significant association with an elevated risk of PC among general population exposed to Cd. Cadmium exposure of laboratory animals was showed to cause PC supporting the findings suggested by human studies. The concordance with human and animal studies is buttressed by in vitro studies, although in vitro data interpretation is problematic. In most instances, only significant effects are reported, and the concentrations of Cd are excessive, which would skew interpretation. Previous reports suggest that oxidative stress, apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd-mediated carcinogenesis. Undoubtedly, a significant amount of work is still needed to achieve a better understanding of the Cd involvement in pancreatic cancer which could facilitate prevention, diagnosis, and therapy of this fatal disease.
T oxoplasma gondii is a protozoan parasite distributed worldwide and infecting one-third of the global population. Infection is acquired by ingestion of parasites via consumption of undercooked meat containing tissue cysts or of water, fruits, or vegetables contaminated with oocysts. In immunocompetent individuals, primary infection results in the formation of tissue cysts and in serological evidence of infection. However, in immunocompromized patients, such as hematopoietic stem cell transplant (HSCT) recipients, toxoplasmosis is often a life-threatening opportunistic infection arising either from transmission of the parasites via a graft from a seropositive donor to a seronegative recipient or, far more frequently, from reactivation of a preexisting latent infection in a seropositive recipient, regardless of the donor's serological status (1). After allogeneic HSCT, studies have shown an incidence of invasive toxoplasmosis among seropositive recipients of 4% to 6%, with an estimated mortality rate of 60% to 90% (2, 3).Nijmegen breakage syndrome (NBS) is a rare, autosome-recessive DNA repair disorder characterized by microcephaly with normal intelligence, facial dysmorphia (bird-like facial features), primary immunodeficiency, and a predisposition to lymphoid malignancies at a young age (4, 5). Treatment of NBS-related malignancies is challenging due to the chromosomal instability and immunodeficiency which make the patients more susceptible to the toxic effects of standard chemotherapy and radiation. Although lymphoid malignancies occurring in NBS patients can be successfully brought into remission using standard chemotherapy regimens with minor dose modifications (6, 7), a high rate of treatment failure and relapse has been observed (8). An alternative treatment option for malignancies in NBS is HSCT from HLAidentical donors, which has been shown not only to correct humoral and cellular immunodeficiency but also to lower the secondary malignancy rate (9).We here present a case of an early and fulminant post-HSCT reactivation of toxoplasmosis caused by an atypical T. gondii strain in a young patient with NBS that contributed to a subsequent fatal outcome within 40 days after transplantation. This case is the first report of increased clinical severity of toxoplasmosis caused by an atypical strain in the setting of immunosuppression. It also stresses the value and necessity of the use of quantitative molecular methods to monitor T. gondii reactivation in cases of reactivation risk.(The results of this study have been presented in part at the 11th European Multicolloquium of Parasitology [EMOP XI],
The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary-care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.
Previous studies demonstrated insulin resistance and increased prevalence of impaired glucose tolerance and type 2 diabetes mellitus in patients with primary hyperparathyroidism (PHPT). The effect of curative parathyroidectomy on insulin sensitivity was associated with conflicting results depending on which method for measuring the insulin sensitivity has been used. There was no improvement using HOMA and QUICKI while minimal model demonstrated significant improvement in insulin sensitivity. The aim of our study was to evaluate the insulin sensitivity before and after parathyroidectomy in patients with PHPT using a euglycemic clamp. 44 patients with PHPT and 11 age and body mass index matched healthy controls participated in study protocol. Before surgery M values and HOMA IR suggest insulin resistance in patients with PHPT. There was no difference in M index (3.74±1.89 vs. 4.62±2.27, p>0.05), HOMA IR (2.94±1.39 vs. 3.29±0.81, p>0.05), AUC glucose (863.0±261.3 vs. 842.3±165.5, p>0.05), AUC insulin (7068.7±4159.0 vs. 7229.6±2581.7, p>0.05), ISI (4.73±2.77 vs. 4.25±2.94, p>0.05) and AIR (47.89±32.05 vs. 38.96±21.20, p>0.05) between patients with PHPT and HC. There was significant improvement in insulin sensitivity after parathyroidectomy but both preoperative and postoperative M values were not significantly different in comparison to HC. There were no significant changes in HOMA IR, AUC glucose, AUC insulin, ISI and AIR before and after therapy. In conclusion, we observed significant improvement in insulin sensitivity after parathyroidectomy in patients with PHPT. There was no difference in parameters of insulin secretion before and after parathyroidectomy in patients with PHPT.
Aim: We conducted a prospective study to evaluate the causes and outcome in children with fever of unknown origin (FUO). Methods: From 1990 to 1999, 185 children with FUO were evaluated. Initial evaluation included routine haematological analysis, Epstein‐Barr virus (EBV) serology, urine, stool or blood cultures, chest X‐ray and tuberculin probe. Results: In 131 (70%) patients diagnosis was established, and 70 (37.8%) had infectious disease. EBV infection was the most common infection followed by visceral leishmaniasis (VL), urinary tract infection (UTI) and tuberculosis. Autoimmune disorders were diagnosed in 24 (12.9%), Kawasaki disease in 12 (6.4%), malignant diseases in 12 (6.4%) and miscellaneous conditions in 15 (8.1%) patients. In the remaining 54 (30%) patients, diagnosis was not established and most of them had self‐limited disease. During the investigation, 26 (14%) patients developed serious organ dysfunction and five patients (two with virus‐associated haemophagocytic syndrome, one with VL and two unknown) died.
Conclusion: The most important infectious causes of FUO in our study were EBV infection and VL. Kawasaki disease represented a significant cause of FUO at the beginning of our study because it was not recognized by primary‐care physicians. We report myelodysplastic syndrome as another emerging cause of paediatric FUO. Repeated clinical examination and careful use of specific laboratory examinations, invasive diagnostic procedures or imaging are crucial in approaching paediatric FUO.
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