Juvenile Myelomonocytic Leukemia with PTPN11 Mutation in a 23-Month-Old Girl

Juvenile myelomonocytic leukemia (JMML) is a rare clonal myeloproliferative disorder affecting young children. The natural course of JMML is rapidly fatal with 80% of patients surviving less than three years. Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment of JMML. We report a case of a 23-month-old girl who presented with an upper respiratory tract infection, fever, rash, diarrhea, hepatosplenomegaly and abdominal distention. Severe elevation of white blood cell count with monocytosis and myeloid progenitors in the peripheral blood was also detected. Bone marrow smear showed morphology suggestive of JMML, an unspecific immune phenotype and a normal karyotype. DNA analysis revealed a mutation in the PTPN11 gene. Therefore, the final diagnosis of JMML with somatic PTPN11 mutation was established. Following three months of cytostatic therapy with 6-mercaptopurine and low doses of cytarabine partial remission was achieved and allogeneic HSCT was successfully performed. Six months after the diagnosis, the girl was in a good condition and in a complete remission of JMML. Early diagnosis and allogeneic HSCT were crucial for successful treatment outcome

Pre-B-cell acute lymphoblastic leukemia with bulk extramedullary disease and chromosome 22 (EWSR1) rearrangement masquerading as Ewing sarcoma

We report a 2-year-old female with a subcutaneous tumor who was initially misdiagnosed as suffering from Ewing sarcoma with a positive EWSR1 rearrangement and EWS/FLI1 transcript. After finding lymphoblasts in peripheral blood, the diagnosis of acute lymphoblastic leukemia was established. This necessitated further analysis of the subcutaneous tumor. The tissue was positive for immature B-cell markers and an immunoglobulin heavy chain gene rearrangement, which confirmed the final diagnosis of common type acute lymphoblastic leukemia with bulk extramedullary disease. The patient was treated with chemotherapy and was in remission 30 months after the diagnosis

Bol i palijativna medicina – tempus projekt u Hrvatskoj

Pain and Palliative Medicine Project (PPMP), funded by the TEMPUS programme of the European Union, has been established with a goal of sharing knowledge and experience from countries in which palliative care is already substantially developed to partner countries whose palliative care encountered more problems. Croatia as partner country, has tried to improve national palliative care systems through education of medical and non-medical personnel. Protocols of collaboration and training courses in pain management and palliative medicine at the Universities of Florence and Lyon, including options of collaboration with some university and clinical institutions in Croatia have been presented. After their two-year project, the Croatian team has noted significant progress in the fields of education, infrastructure and legislative support for development of palliative care. These results show the need for improving Croatian palliative care system as well as possible solutions for overcoming obstacles derived from nation’s traditional views on the treatment of the terminally ill.Bol i palijativna medicina (PPMP) je projekt u okviru TEMPUS programa Europske Unije s ciljem prenošenja znanja i iskustava zemalja, u kojima je palijativna skrb dobro razvijena, zemljama u kojima je palijativna skrb manje aktivna. Hrvatska, kao zemlja partner, nastoji poboljšati nacionalni program palijativne skrbi kroz edukaciju medicinskog i ne-medicinskog osoblja. Prikazani su protokoli suradnje i tečajeva o boli i palijativnoj medicine na Sveučilištima u Firenci i Lyonu, kao i na nekim sveučilišnim i kliničkim institucijama u Hrvatskoj. Nakon dvogodišnjeg projekta hrvatski tim zabilježio je značajni napredak u poljima edukacije, infrastrukture i zakonske potpore razvoju palijativne skrbi. Ovi rezultati su pokazali potrebu za daljnjim poboljšavanjem hrvatske palijativne skrbi kao i moguća rješenja za prevladavanje prepreka koje proizlaze iz tradicionalnih pogleda društva na skrb terminalno bolesnih

Bol i palijativna medicina – tempus projekt u Hrvatskoj

Pain and Palliative Medicine Project (PPMP), funded by the TEMPUS programme of the European Union, has been established with a goal of sharing knowledge and experience from countries in which palliative care is already substantially developed to partner countries whose palliative care encountered more problems. Croatia as partner country, has tried to improve national palliative care systems through education of medical and non-medical personnel. Protocols of collaboration and training courses in pain management and palliative medicine at the Universities of Florence and Lyon, including options of collaboration with some university and clinical institutions in Croatia have been presented. After their two-year project, the Croatian team has noted significant progress in the fields of education, infrastructure and legislative support for development of palliative care. These results show the need for improving Croatian palliative care system as well as possible solutions for overcoming obstacles derived from nation’s traditional views on the treatment of the terminally ill.Bol i palijativna medicina (PPMP) je projekt u okviru TEMPUS programa Europske Unije s ciljem prenošenja znanja i iskustava zemalja, u kojima je palijativna skrb dobro razvijena, zemljama u kojima je palijativna skrb manje aktivna. Hrvatska, kao zemlja partner, nastoji poboljšati nacionalni program palijativne skrbi kroz edukaciju medicinskog i ne-medicinskog osoblja. Prikazani su protokoli suradnje i tečajeva o boli i palijativnoj medicine na Sveučilištima u Firenci i Lyonu, kao i na nekim sveučilišnim i kliničkim institucijama u Hrvatskoj. Nakon dvogodišnjeg projekta hrvatski tim zabilježio je značajni napredak u poljima edukacije, infrastrukture i zakonske potpore razvoju palijativne skrbi. Ovi rezultati su pokazali potrebu za daljnjim poboljšavanjem hrvatske palijativne skrbi kao i moguća rješenja za prevladavanje prepreka koje proizlaze iz tradicionalnih pogleda društva na skrb terminalno bolesnih

Neprepoznati prijelom posteromedijalnog nastavka talusa: prikaz slučaja i pregled literature

In this report, we present a rare case of an initially unrecognized fracture of the posteromedial process of the talus sustained in a seldom reported position of dorsiflexion and supination of the foot. Fractures of the posteromedial process of the talus are very rare and represent an important diagnostic problem. Difficult x-ray visualization makes these fractures often misdiagnosed as ankle sprains. Complications due to this kind of fractures can include serious consequences such as avascular osteonecrosis, tarsal tunnel syndrome, post-traumatic osteoarthritis, or chronic pain. Timely diagnosis represents an important factor in the development of these conditions. A heightened awareness in examining ankle traumas with specific patient history details is of great importance. The most common mechanism of injury includes dorsiflexion and pronation of the foot. However, in an increasing number of cases alternative mechanisms have been described, all including high-energy impacts. Our patient sustained a fracture of the posteromedial process of the talus in dorsiflexion and supination with high-energy impact due to a 3-m fall. The patient was treated with excision of the fragment six months after the injury, and 18 months after the surgery the patient returned to his normal daily activities with significantly less pain in the posteromedial part of the ankle.U ovom prikazu opisujemo rijedak slučaj prvotno neprepoznatog prijeloma posteromedijalnog nastavka talusa zadobivenog u položaju dorzifleksije i inverzije stopala. Prijelomi posteromedijalnog nastavka talusa su iznimno rijedak i važan dijagnostički problem. Poradi otežane radiološke vizualizacije često se pogrešno dijagnosticiraju i to najčešće kao distorzija gležnja. Komplikacije ovakvih prijeloma mogu biti ozbiljne, a kao najčešće i najozbiljnije ističu se nastanak avaskularne nekroze kosti, sindrom tarzalnog tunela, poslijetraumatski osteoartritis ili kronična bol. Stoga je pravodobna dijagnoza od iznimne važnosti da bi se izbjegle moguće komplikacije. Potrebna je veća pozornost pri probiru ozljeda gležnja sa specifičnim anamnestičkim detaljima. Najčešći mehanizam nastanka ovakvog prijeloma je dorzifleksija i everzija stopala. Međutim, u sve većem broju slučajeva opisuju se i drugačiji mehanizmi ozljede koji uključuju prijenos jake mehaničke sile. Naš bolesnik je zadobio prijelom posteromedijalnog nastavka talusa u rijetko opisanoj dorzifleksiji i inverziji, s prijenosom jake mehaničke sile, prilikom pada s 3 metra visine. Isprva je pogrešno liječen zbog distorzije talokruralnog zgloba, a poradi kontinuirane boli učinjena je ekscizija fragmenta šest mjeseci nakon ozljede. Osamnaest mjeseci nakon zahvata bolesnik se u potpunosti vratio svakodnevnim aktivnostima uza značajno manju bolnost u posteromedijalnom dijelu gležnja

Familial Hemophagocytic Lymphohistiocytosis in a 6-Week-Old Male Infant

Familial hemophagocytic lymphohistiocytosis (FLH) is an autosomal recessively inherited multisystem disease. This defect in cellular cytotoxicity is a life threatening condition characterized by fever, rash, splenomegaly, cytopenias and neurologic manifestations. PRF1, UNC13D and STX11 gene defects underlie in about 40–50% of primary cases. Chemoimmunotherapy followed by hematopoietic stem cell transplantation improved disease outcome. We report a case of a 6-week-old boy who presented with a fever, diffuse rash, disseminated intravascular coagulation, hypofibrinogenemia, hypertrigliceridemia, hepatosplenomegaly, leukocytosis with 90% of lymphocytes, granulocytopenia, anemia, trombocytopenia, hyperferritinemia and pathological findings in cerebrospinal fluid. The patient had decreased frequency of NK cells and low NK cell activity in peripheral blood. Bone marrow aspiration analysis showed degenerative changes of histocyte cells, with preserved cytophages (lymphophages and erythrophages) consistent with hematophagocytic syndrome. Given that the molecular diagnosis of the known mutations in genes PRF1 and UNC13D showed a mutation in UNC13D, the diagnosis of familial hemophagocytic lymphohistiocytosis subtype 3 was established. HLH-2004 chemotherapy protocol was performed and partial remission with residual central nervous system disease was achieved. Hematopoietic stem cell transplantation was successfully performed with an unrelated HLA-matched donor. Familiar HLH is generaly a progressive and fatal disease. Early diagnosis with molecular genetic analysis and chemoimmunotherapy followed by hematopoietic stem-cell transplantation is the best approach

Influence of hyperthermal regimes on experimental teratoma development in vitro

We screened for the impact of hyperthermal regimes varying in the cumulative equivalent minutes at 43°C (CEM43°C) and media composition on tumour development using an original teratoma in vitro model. Rat embryos (three germ layers) were microsurgically isolated and cultivated at the air-liquid interface. During a two week period, ectodermal, mesodermal and endodermal derivatives developed within trilaminar teratomas. Controls were grown at 37°C. Overall growth was measured, and teratoma survival and differentiation were histologically assessed. Cell proliferation was stereologically quantified by the volume density of Proliferating Cell Nuclear Antigen. Hyperthermia of 42°C, applied for 15 minutes after plating (CEM43°C 3.75 minutes), diminished cell proliferation (P ˂ .0001) and enhanced differentiation of both myotubes (P ˂ .01) and cylindrical epithelium (P ˂ .05). Hyperthermia of 43°C applied each day for 30 minutes during the first week (CEM43°C 210 minutes) impaired overall growth (P ˂ .01) and diminished cell proliferation (P ˂ .0001). Long-term hyperthermia of 40.5°C applied for two weeks (CEM43°C 630 minutes) significantly impaired survival (P ˂ .005). Long-term hyperthermia of 40.5°C applied from the second day when differentiation of tissues begins (CEM43°C 585 minutes) impaired survival (P ˂ .0001), overall growth (P ˂ .01) and cartilage differentiation (P ˂ .05). No teratomas survived extreme regimes: 43°C for 24 hours (CEM43°C 1440 minutes), hyperthermia in the scant serum-free medium (CEM43°C 630 minutes) or treatment with an anti-HSP70 antibody before long-term hyperthermia 40.5°C from the second day (CEM43°C 585 minutes). This in vitro research provided novel insights into the impact of hyperthermia on the development of experimental teratomas from their undifferentiated sources and are thus of potential interest for future therapeutic strategies in corresponding in vivo models