Transfusion reactions in newborns

Transfuzija krvnih pripravaka je siguran i učinkovit postupak liječenja. Međutim, transfuzija može imati i neželjenih posljedica. Za razliku od odraslih i starije djece, u novorođenčadi se rijetko javljaju imunološke transfuzijske reakcije, jer oni izuzetno rijetko stvaraju aloprotutijela zbog nezrelosti imunološkog sustava. Stoga su imunološke transfuzijske reakcije koje se u njih jave češće posljedica pasivnog prijenosa protutijela transfuzijom krvnog pripravka koji sadrži plazmu, nego protutijela koje je stvorilo dijete. Metaboličke komplikacije, koje su rijetke u odraslih, mnogo su češće u novorođenčadi zbog nezrelosti njihovih organskih sustava. Nedonoščad je osobito rizična za nastanak metaboličkih komplikacija, ona zbog nezrelosti mogu imati poteškoće u učinkovitom metaboliziranju različitih tvari što se nalaze u antikoagulantnim i aditivnim otopinama koje se primjenjuju za pohranu krvnih pripravaka. Rizik za prijenos hepatitisa i AIDS-a transfuzijom krvih pripravaka koji su testirani na biljege ovih zaraznih bolesti danas je vrlo nizak. Na žalost, još i sad postoji mogućnost prijenosa nepoznatih mikroorganizama transfuzijom krvi. Tijekom i nakon svake transfuzije treba pratiti primatelja zbog pojave simptoma i znakova koji bi upućivali na eventualnu transfuzijsku reakciju. Donošenje odluke o transfuzijskom liječenju bolesnika, bez obzira je li riječ o novorođenčetu, starijem djetetu ili odrasloj osobi, zahtijeva da se uz sve prednosti razmotre i moguće posljedice tranfuzijskog liječenja.The transfusion of blood components is a safe and life-saving procedure. However, it may lead to an adverse outcome. Some of the more frequent acute immunologic transfusion reactions that are seen in older children and adults, such as febrile or allergic reactions, are rarely reported in the newborn. When these reactions do occur, they are usually the result of passively acquired antibodies infused into a relatively small plasma volume, rather than of antibodies produced by the infant. Newborns, on the other hand, may be more vulnerable to metabolic or physiologic complications as a result of the immature nature of their organ systems. The immature development of several organ systems in the premature infant has led to many concerns relating to the infant\u27s ability to efficiently metabolize various compounds present in the anticoagulants and preservatives used for the storage of blood components. The risks for transfusion-related infection from screened donations for hepatitis B virus, hepatitis C virus and human immunodeficiency virus are today very low. Unfortunately, the potential still exists for previously unknown microorganisms to be transmitted via transfusion. All transfusions should be carefully monitored, and adverse reactions to blood components should be appropriately investigated. The decision to transfuse a patient, whether the patient is a newborn, an older child, or an adult, requires considering both the risks and the intended benefits of the transfusion

Transfusion reactions in newborns

Transfuzija krvnih pripravaka je siguran i učinkovit postupak liječenja. Međutim, transfuzija može imati i neželjenih posljedica. Za razliku od odraslih i starije djece, u novorođenčadi se rijetko javljaju imunološke transfuzijske reakcije, jer oni izuzetno rijetko stvaraju aloprotutijela zbog nezrelosti imunološkog sustava. Stoga su imunološke transfuzijske reakcije koje se u njih jave češće posljedica pasivnog prijenosa protutijela transfuzijom krvnog pripravka koji sadrži plazmu, nego protutijela koje je stvorilo dijete. Metaboličke komplikacije, koje su rijetke u odraslih, mnogo su češće u novorođenčadi zbog nezrelosti njihovih organskih sustava. Nedonoščad je osobito rizična za nastanak metaboličkih komplikacija, ona zbog nezrelosti mogu imati poteškoće u učinkovitom metaboliziranju različitih tvari što se nalaze u antikoagulantnim i aditivnim otopinama koje se primjenjuju za pohranu krvnih pripravaka. Rizik za prijenos hepatitisa i AIDS-a transfuzijom krvih pripravaka koji su testirani na biljege ovih zaraznih bolesti danas je vrlo nizak. Na žalost, još i sad postoji mogućnost prijenosa nepoznatih mikroorganizama transfuzijom krvi. Tijekom i nakon svake transfuzije treba pratiti primatelja zbog pojave simptoma i znakova koji bi upućivali na eventualnu transfuzijsku reakciju. Donošenje odluke o transfuzijskom liječenju bolesnika, bez obzira je li riječ o novorođenčetu, starijem djetetu ili odrasloj osobi, zahtijeva da se uz sve prednosti razmotre i moguće posljedice tranfuzijskog liječenja.The transfusion of blood components is a safe and life-saving procedure. However, it may lead to an adverse outcome. Some of the more frequent acute immunologic transfusion reactions that are seen in older children and adults, such as febrile or allergic reactions, are rarely reported in the newborn. When these reactions do occur, they are usually the result of passively acquired antibodies infused into a relatively small plasma volume, rather than of antibodies produced by the infant. Newborns, on the other hand, may be more vulnerable to metabolic or physiologic complications as a result of the immature nature of their organ systems. The immature development of several organ systems in the premature infant has led to many concerns relating to the infant\u27s ability to efficiently metabolize various compounds present in the anticoagulants and preservatives used for the storage of blood components. The risks for transfusion-related infection from screened donations for hepatitis B virus, hepatitis C virus and human immunodeficiency virus are today very low. Unfortunately, the potential still exists for previously unknown microorganisms to be transmitted via transfusion. All transfusions should be carefully monitored, and adverse reactions to blood components should be appropriately investigated. The decision to transfuse a patient, whether the patient is a newborn, an older child, or an adult, requires considering both the risks and the intended benefits of the transfusion

Analysis of concept maps with textbooks to identify possible conceptual links to facilitate understanding of the reproduction process

Cilj ovog istraživanja je analiza konceptualnih mapa uz udžbenike Biologije za osnovnu školu u svrhu utvrđivanja mogućih konceptualnih poveznica za olakšano učenje. U ranijem istraživanju utvrđeno je postojanje problema kod usvojenosti koncepta razmnožavanje te su kao najizraženije uočene miskoncepcije uz ključni koncept životni ciklus stanice i organizma te kod razumijevanja koncepta oplodnje. Utvrđene miskoncepcije ukazuju na nužnu promjenu organizacije nastavnih sadržaja biologije, kao i na potrebu uvođenja novih nastavnih strategija s naglaskom na aktivno sudjelovanje učenika. S obzirom na ograničenja nastavnog plana i programa prema kojem su mape pripremane kao sistematizacija uz nastavne teme, a ne kao podrška izgradnji ciljanog koncepta, uočeni problemi nisu u potpunosti podržani, iako omogućavaju 73 % uspješno učenje uz djelomično razrješenje uočenih problema, pod uvjetom da se pravilno primjenjuju u nastavi. U pripremi konceptualne mape prema kurikulumu Biologije koji podržava konceptualni pristup učenju procijenjeno je da pripremljena ekspertna mapa podržava učenje uz razrješenje mogućih miskoncepcija u udjelu većem od 87 %.This research aims to analyze expert concept maps for a primary school to identify possible conceptual links for facilitated learning. Previous research has identified problems with the adoption of the concept of reproduction and as the most pronounced misconceptions with the key concept of the life cycle of the cell and organism and in understanding the concept of fertilization. The identified misconceptions indicate the necessary change in the organization of biology teaching contents, as well as the need to introduce new teaching strategies with an emphasis on the active participation of students. Given the limitations of the valid national teaching documents before 2019., according to which maps are prepared as a systematization with teaching topics, and not to support the construction of a targeted concept, the identified problems are not fully supported. Expert concept maps allow 73% successful learning with partial resolution of identified problems, provided properly applied in teaching. In the analyze of the concept map according to the curriculum of Biology after 2019., which supports conceptual learning approach, it is estimated that the prepared expert map supports learning with the resolution of possible misconceptions in the proportion greater than 87%

Collection and composition of autologous peripheral blood stem cells graft in patients with acute myeloid leukemia: influence on hematopoietic recovery and outcome [Skupljanje i sastav transplantata autolognih krvotvornih matičnih stanica periferne krvi u bolesnika s akutnom mijeloičnom leukemijom: utjecaj na hematološki oporavak i ishod]

Hematopoietic stem cell (HSC) transplantation is a standard approach in the treatment of hematological malignant diseases. For the last 15 years the main source of cells for trasplantation have been peripheral blood stem cells (PBSC). With the availability of hematopoietic growth factors and understanding the advantages of treatment with PBSC, the application of bone marrow (BM) was supplanted. The aim of this survey was to explore the success of PBSC collection, the factors which influence the success of PBSC collection, the composition and the quality of graft and their infuence on hematopoietic recovery and outcome after transplantation in patients with acute myeloid leukemia (AML). PBSC were collected by the method of leukapheresis after applying a combination of chemotherapy and growth factors or only growth factors. The quality of graft was determined with the clonogenic progenitor cell assay and with the flow citometry analysis. Of the total 134 patients with AML, who were submitted to HSC mobilization, the collection was successful in 78 (58.2%) patients. The collection was more successful after the first than after the second attempt of HSC mobilization (49% vs. 11%). The criteria for effective mobilization were the number of leukocytes >3´109/L and the concentration of CD34+ cells >20´103/mL in the peripheral blood on the first day of leukapheresis. The number of CD34+ cells infused had the strongest impact on hematopoietic recovery. We noted significantly faster hematological recovery of neutrophils and platelets, fewer number of transfused units of red blood cells and platelets, shorter duration of the tranfusion support, shorter treatment with intravenous antibiotic therapy and shorter hospitalization after PBSC compared to BM transplantation. These advantages could provide their standard application in the treatment of patients with AML

Understanding of life cycles and fertilization during learning biology in primary school

Cilj ovog istraživanja je odrediti usvojenost i konceptualno razumijevanje makrokoncepta Razmnožavanje i razvoj organizma među učenicima 7. i 8. razreda osnovnih škola, na temelju učeničkih odgovora na pitanja uz makrokoncept Razmnožavanje i razvoj organizma na Županijskom natjecanju iz biologije 2015. i 2017. godine. Analiza učeničkih odgovora uključivala je specifično kodiranje odgovora i tumačenje biološkog značenja odgovora učenika. Izdvojeni su i objašnjeni problemi koje učenici pokazuju u svojim odgovorima kao i njihove miskoncepcije vezane uz koncept razmnožavanje. Utvrđeno je i opisano postojanje niza problema kod usvojenosti koncepta razmnožavanje te su kao najizraženije uočene miskoncepcije uz ključni koncept životni ciklus stanice i organizma te kod razumijevanja koncepta oplodnje. Utvrđene miskoncepcije ukazuju na nužnu promjenu organizacije nastavnih sadržaja biologije, kao i na potrebu uvođenja novih nastavnih strategija s naglaskom na aktivnost i samostalni rad učenika.The aim of this study was to determine the conceptual understanding of the macro concept of Reproduction and organism development among students of the 7th and 8th grade of primary schools, based on students\u27 answers to questions in relation to the macro concept of Reproduction and organism development at the regional competition in Biology in 2015 and 2017. Analysis of the students\u27 answers included specific coding of the answers and interpreting the biological importance and meaning of each answer. Problems and misconceptions in relation to the concept of reproduction were singled out and explained. The analysis showed there is a problem with understanding the concept of reproduction and the misconceptions based around the key concept of cell life cycle, as well as misunderstandings of the concept of fertilization were observed as most prominent. Misconceptions found in this study show the necessity of changing the organization of contents taught in primary school biology and the need for using new teaching strategies, based on the students’ activity and individual work

Prijetransfuzijsko ispitivanje i transfuzijsko liječenje pri primjeni monoklonskog protutijela anti-CD38

Daratumumab je prvo monoklonsko protutijelo anti-CD38 koje se primjenjuje u liječenju multiplog mijeloma. Njegova primjena uzrokuje panreaktivnost u testovima prijetransfuzijskog ispitivanja. Panreaktivnost je posljedica vezanja monoklonskog protutijela anti-CD38 na protein CD38 na površini eritrocita, što u standardnom testiranju onemogućuje otkrivanje antieritrocitnih aloprotutijela i osiguranje podudarne krvi za transfuzijsko liječenje. Cilj rada bila je retrospektivna analiza vlastitih iskustava u rješavanju smetnja prijetransfuzijskog ispitivanja uzrokovanih monoklonskim protutijelom anti-CD38 i u transfuzijskom liječenju tih bolesnika. Prikazani su postupci za prijetransfuzijsko ispitivanje i transfuzijsko liječenje bolesnika liječenih monoklonskim protutijelom anti-CD38 koji su provedeni u Kliničkome bolničkom centru Zagreb. U istraživanju je analizirano 10-ero bolesnika liječenih daratumumabom. Prije i poslije primjene daratumumaba pretražena su antieritrocitna protutijela i određen je direktan antiglobulinski test. Pri transfuzijskom liječenju napravljeni su test pretraživanja antieritrocitnih protutijela i križne reakcije standardnim testiranjem i specifičnim postupcima imunohematoloških ispitivanja za uklanjanje smetnja monoklonskog protutijela anti-CD38. Postupci su uključivali obradu eritrocita ditiotreitolom koncentracije 0,2 M i neutralizacijski test uz primjenu reagensa DaraEx. Kod svih bolesnika testovi pretraživanja antieritrocitnih protutijela i križne reakcije bili su nakon primjene daratumumaba pozitivni, dok je direktan antiglobulinski test zbog primjene daratumumaba bio pozitivan u gotovo polovine bolesnika. Nakon obrade eritrocita ditiotreitolom 0,2 M učestalost lažno pozitivnih rezultata testova pretraživanja antieritrocitnih protutijela i križnih reakcija iznosila je oko 40%, a poslije primjene reagensa DaraEx oko 20%. Oba specifična postupka, obrada eritrocita ditiotreitolom 0,2 M i neutralizacijski test primjenom reagensa DaraEx, nisu se pokazala dovoljno pouzdanima u rješavanju smetnja uzrokovanih monoklonskim protutijelom anti-CD38. Zato je za transfuzijsko liječenje tih bolesnika nužno osigurati eritrocitne pripravke podudarne prema klinički najvažnijim antigenima u sustavima krvnih grupa Rh, Kell, Kidd, Duffy i MNS. Dobra suradnja između odjela i transfuzijske službe te postojanje protokola za prijetransfuzijsko ispitivanje i transfuzijsko liječenje ostaju preduvjet za pravodobno i sigurno transfuzijsko liječenje te skupine bolesnika

Collection and Composition of Autologous Peripheral Blood Stem Cells Graft in Patients with Acute Myeloid Leukemia: Influence on Hematopoietic Recovery and Outcome

Hematopoietic stem cell (HSC) transplantation is a standard approach in the treatment of hematological malignant diseases. For the last 15 years the main source of cells for trasplantation have been peripheral blood stem cells (PBSC). With the availability of hematopoietic growth factors and understanding the advantages of treatment with PBSC, the application of bone marrow (BM) was supplanted. The aim of this survey was to explore the success of PBSC collection, the factors which influence the success of PBSC collection, the composition and the quality of graft and their infuence on hematopoietic recovery and outcome after transplantation in patients with acute myeloid leukemia (AML). PBSC were collected by the method of leukapheresis after applying a combination of chemotherapy and growth factors or only growth factors. The quality of graft was determined with the clonogenic progenitor cell assay and with the flow citometry analysis. Of the total 134 patients with AML, who were submitted to HSC mobilization, the collection was successful in 78 (58.2%) patients. The collection was more successful after the first than after the second attempt of HSC mobilization (49% vs. 11%). The criteria for effective mobilization were the number of leukocytes >3´109/L and the concentration of CD34+ cells >20´103/mL in the peripheral blood on the first day of leukapheresis. The number of CD34+ cells infused had the strongest impact on hematopoietic recovery. We noted significantly faster hematological recovery of neutrophils and platelets, fewer number of transfused units of red blood cells and platelets, shorter duration of the tranfusion support, shorter treatment with intravenous antibiotic therapy and shorter hospitalization after PBSC compared to BM transplantation. These advantages could provide their standard application in the treatment of patients with AML

EXTRACORPOREAL PHOTOPHERESIS IN TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE

Ekstrakorporalna fotofereza (EF) jest imunomodulatorna terapija koja se rabi u liječenju kronične reakcije transplantata protiv primatelja (engl. chronic graft versus host disease, cGVHD). Tijekom EF-a leukaferezom se iz krvi izdvajaju mononuklearne stanice, ex vivo im se dodaje 8-metoksipsoralen, stanice se ozrače UVA-zrakama i potom reinfundiraju bolesniku. Cilj istraživanja bio je procijeniti klinički i imunomodulatorni učinak postupka EF-a u bolesnika s cGVHD-om. Analiziran je 341 postupak EF-a u 7 bolesnika s cGVHD-om s medijanom EF-a po bolesniku 37 (raspon 13–131). U svih bolesnika cGVHD se manifestirao kožnim promjenama u kombinaciji sa simptomima drugih organskih sustava. EF su provođene dva dana za redom: prvih mjesec dana svaki tjedan, sljedeća 2 mjeseca svaki drugi tjedan, a potom jednom na mjesec. Medijan trajanja liječenja postupkom EF-a iznosio je 10 mjeseci (raspon 2 do 58). EF je većinom povoljno utjecao na simptome cGVHD-a pa je u 6 bolesnika došlo do poboljšanja i/ili stabilizacije promjena kože te bolje pokretljivosti zglobova, a u 2 bolesnika s ulceracijama sluznice usne šupljine promjene su se u cijelosti povukle. Do kliničkog poboljšanja došlo je 2 do 3 mjeseca nakon početka EF-a, što je omogućilo značajno smanjenje ili prestanak primjene glukokortikoida. Neželjene reakcije javile su se tijekom 4,9% postupaka. U bolesnika u kojih je došlo do poboljšanja kliničkog stanja normalizirale su se vrijednosti omjera CD4+/CD8+ stanica, kao i broj NK-stanica. Rezultati našeg istraživanja pokazuju da primjena EF-a povoljno utječe na simptome cGVHD-a i omogućuje sniženje doze kortikosteroida uz poboljšanje kvalitete života bolesnika pa se stoga može preporučiti za bolesnike koji ne odgovaraju na standardno liječenje.Extracorporeal photopheresis (ECP) is an immunomodulatory therapy which has been used in the treatment of chronic GVHD (cGVHD). ECP involves separation of the mononuclear cells with leukapheresis, followed by ex vivo administration of 8-methoxypsoralen and UV-A radiation and reinfusion to the patient. Aim of the study was to evaluate clinical and immunomodulatory effect of ECP procedures in patients with cGVHD. We analyzed 341 ECP procedures performed in 7 patients with cGVHD; median ECP per patient was 37 (range 13–131). All patients suffered from skin changes in combination with impaired joint mobility and symptoms of oral disease. ECP procedures were performed for two consecutive days: in initial phase weekly, followed by every two weeks and than monthly according to clinical response. Median of ECP treatment duration was 10 months (range 2–58). The effect of ECP in patients with cGVHD with skin and joint involvement was mostly beneficial: 6 patients experienced either improvement or stabilization in skin changes and joint mobility. In 2 patients who suffered from oral disease, the total recovery was observed. Clinical response was typically delayed until 2 to 3 months, and reduction in glucocorticoid dose was observed. Adverse reactions were observed in 4.9% procedures. In patients who responded to ECP treatment, CD4+/CD8+ ratio and number of NK cells were normalized. ECP proved to be an efficient and safe procedure that may be recommended for patients with cGVHD who do not respond to conventional therap

Leukocitafereza u liječenju teškog, o steroidima ovisnog ulceroznog kolitisa

Ulcerative colitis (UC) is a multifactorial disease of unknown precise etiology and immunopathogenesis. Peripheral blood granulocytes and monocytes/macrophages are the major sources of cytokines, which regulate inflammation. Leukocytapheresis (LCAP) is a method where blood is processed by apheresis system that removes lymphocytes and plasma before being returned to the body. We report the first case in Croatia where we used LCAP in the treatment of a patient with severe steroid-dependent UC. After 12 LCAP procedures, good clinical response was obtained and there were no significant adverse side effects noticed. The patient remained in clinical remission over two years in which he underwent regular follow ups at outpatient clinic. Over a 10-year follow-up period after LCAP, the patient had only occasional clini-cal symptoms of disease activity. The clinical course was complicated with the development of metastatic colorectal carcinoma, which points to the importance of regular disease monitoring rather than the in-creased risk of malignant disease after LCAP. Patients with UC are a demanding group of patients that warrant the search for novel treatment strategies other than conventional pharmacological therapies. Alt-hough LCAP is still not a common treatment modality in our daily practice, data from recent studies sug-gest it to be an effective and safe procedure in the management of active UC patients.Ulcerozni kolitis (UC) je kronična bolest multifaktorske etiologije čiji detaljan mehanizam imunološkog procesa još nije sasvim razjašnjen, ali ključnu ulogu svakako imaju granulociti i monociti/makrofazi koji reguliraju i pojačavaju upalni proces lučenjem proupalnih citokina. Leukocitofereza (LCAP) je terapijski postupak kojim se prolaskom krvi kroz sustav za aferezu odstranjuju limfociti i plazma prije nego što se krv ponovno vrati u krvotok. U ovom radu je prikazan o steroidima ovisan bolesnik s teškim relapsom UC-a koji je, prvi put u Hrvatskoj, liječen protokolom LCAP. Nakon 12 terapijskih protokola LCAP kod bolesnika je došlo do značajnog kliničkog poboljšanja bez razvo-ja nuspojava. Bolesnik je ostao u kliničkoj remisiji tijekom dvije godine ambulantnog praćenja, a unutar 10 godina praćenja nakon LCAP bolesnik je imao tek povremene simptome aktivnosti bolesti. Klinički tijek bio je kompliciran razvojem metastatskog karcinoma debelog crijeva, što prvenstveno upućuje na važnost redovitog praćenja bolesti, a ne na povećan rizik maligne bolesti nakon LCAP. Bolesnici s UC-om su zahtjevna skupina pacijenata koja zahti-jeva potragu za novim terapijskim strategijama osim onih konvencionalnih farmakoloških. Iako LCAP nije čest modalitet liječenja u svakodnevnoj kliničkoj praksi, novije studije upućuju na to da je postupak učinkovit i siguran u liječenju bolesnika s aktivnim UC-om