Tumori glave i vrata kod djece

Tumori glave i vrata rijetki su u djece. Većina tvorbi zbog kojih roditelji dovode djecu liječniku su benigne, uglavnom upalne etiologije ili kongenitalne, a od novotvorevina je svega 5% malignih. Najčešći maligni tumori vrata i glave kod djece su limfomi, a rjeđe rabdomiosarkomi, histiocitoze, neuroblastomi i retinoblastomi. Simptomi s kojima se djeca javljaju su povećani limfni čvorovi, promuklost, opstrukcija nosnih hodnika, nagluhost, egzoftalmnus, uz opće simptome koji nisu specifični. Laboratorijske i slikovne pretrage pomažu u dijagnozi, ali konačnu dijagnozu maligne bolesti moguće je postaviti tek nakon biopsije. U ovom radu prikazati ćemo učestalost malignih tumora glave i vrata kod djece liječene na Zavodu za hematologiju i onkologiju Klinike za pedijatriju KBC Zagreb u vremenskom razdoblju od 1. siječnja 2016. do 31. prosinca 2020. godine. Od ukupno 47 bolesnika, 27 ih je imalo Hodgkinov limfom koji se javljao u prosječnoj dobi od 15 godina. Drugi po učestalosti su bili retinoblastomi (6 bolesnika, prosječna dob 2 godine), zatim histiocitoze (5 bolesnika, prosječna dob 7 godina), non-Hodgkinovi limfomi (3 bolesnika, prosječna dob 10 godina), te rabdomiosarkomi (2 bolesnika, prosječna dob 3 godine). Po jedan bolesnik imao je nazofaringealni karcinom, sinovijalni sarkom, karcinom štitnjače i dezmoidni tumor. Gledajući dobne skupine, najčešća dob pojavljivanja je između 11. i 18. godine (33 bolesnika), zatim između 1. i 5. godine (8 bolesnika), između 6. i 10. godine (4 bolesnika), te 2 bolesnika kojima se tumor otkrio tijekom 1. godine života (rabdomiosarkom i retinoblastom). Zaključno, benigne novotvorevine glave i vrata su daleko češće od malignih. Pravovremeno postavljenom dijagnozom treba se rano započeti s terapijom, što u konačnici dovodi do boljih rezultata liječenja

Calculating Lumbar Puncture Depth in Children

Lumbar puncture was performed in 195 children and the depth of needle was recorded. Our results show that the depth of lumbar puncture necessary to obtain uncontaminated cerebrospinal fluid correlates best with the child’s weight. The simple formula: mean depth of insertion (cm) = 1.3 + 0.07 x body weight (kg), can be used to estimate the depth of lumbar puncture of children older than 3 months. The depths of lumbar puncture of children younger than 3 months are mostly 1.0–1.5 cm

PARTICULARITIES OF COAGULATION IN CHILDREN

Krvarenja i tromboembolije se pojavljuju kod djece i kod odraslih. Razlog tome mogu biti prirođeni ili stečeni poremećaji. Fiziologija koagulacije i fibrinolize se značajno razlikuje u novorođenčadi i manje djece, od koagulacije i fibrinolize starije djece i odraslih osoba. Sazrijevanjem i rastom djeteta te razlike nestaju. Zbog značajnih fizioloških razlika funkcije trombocita i koncentracije čimbenika koji sudjeluju u koagulaciji i fibrinolizi novorođenčad je istovremeno sklona i krvarenju i nastanku tromboze. Ova dva stanja su kod novorođenčadi međusobno usklađena. Nastanku tromboza kod novorođenčadi pogoduju središnji venski kateteri, sepsa, bolesti jetre, upala i poremećaji tjelesnih tekućina. Hemofilije su najčešće bolesti kod kojih se javljaju opsežna krvarenja. Na njih treba misliti u slučaju nenadanog krvarenja ili pozitivne obiteljske anamneze. U kasnijoj dobi na hemofiliju se mora pomisliti kod dječaka koji pojačano krvare nakon invazivnih postupaka ili traume. Profilaktičko liječenje hemofiličara je postao zlatni standard liječenja i treba započeti što ranije da se prevenira nastanak oštećenja zglobova. Djeca s poremećajima zgrušavanja krvi trebala bi biti podrobno klinički i laboratorijski obrađena da bi se moglo provesti ispravno liječenje. To značajno smanjuje mogućnost nastanka komplikacija i dugoročnih posljedica.Haemorrhagic and thrombotic events occur in both children and adults. The underlying causes are congenital or acquired disorders. The maturation and postnatal development of the human coagulation system results in significant and important differences in the coagulation and fibrinolysis of neonates and young children compared to older children and adults. Platelet function, pro- and anticoagulant protein concentrations and fibrinolytic pathway protein concentrations are developmentally regulated and generate hemostatic homeostasis that is unique to the neonatal period. At the same time, neonates have a predisposition to bleeding and develepment of thrombosis. These differences, which mostly reflect the immaturity of the neonatal haemostasis system, are functionally balanced. Central lines, fluid fluctuations, sepsis, liver dysfunction and inflammation contribute to the risk profile for thrombosis development in ill neonates. Hemophilia is the most common of the severe bleeding disorders and should be considered in the neonatal period in case of unusual bleeding or positive family history. Later, hemophilia should be suspected mainly in males because of abnormal bleeding following invasive procedures. Prophylactic treatment that is started early with clotting-factor concentrates has been shown to prevent hemophilic arthropathy and is therefore the gold standard of care for hemophilia A and B. Children with coagulation disorders should be clinically and laboratory treated according to the exact type and degree of clotting disorder and appropriate treatment should be conducted. This significantly reduces the possibility of acute complications and long-term consequences

Procjena glomerularne filtracije u djece s hemofilijom

Estimated glomerular filtration rate (eGFR) is one of the best-performing methods in evaluating kidney function. There are limited data regarding the estimated glomerular filtration rate in children and young adults with hemophilia. The aim of this study was to determine the difference between three commonly used estimated glomerular filtration rate equations in the pediatric population in a cohort of patients with hemophilia. Our prospective study included 36 pediatric patients with moderate or severe hemophilia. eGFR was calculated for each patient using the original creatinine-based “bedside Schwartz” equation, the cystatin C-based equation and the creatinine-cystatin C-based equation. The difference between the equations, calculated using the one-way repeated ANOVA test, was statistically significant (p <0.001), and post hoc analysis found differences between each method. Correlation analysis showed the strongest positive correlation between the bedside Schwartz equation and creatinine-cystatin C-based equation (r=0.866) among the three methods examined. A correlation between the three eGFR methods was present, but with significant differences between them. Due to the observed differences between eGFR in pediatric patients with hemophilia, further research is needed to find the optimal measurement method for eGFR. Nevertheless, we recommend implementing eGFR equations in routine clinical monitoring of pediatric patients with hemophilia.Procjena glomerularne filtracije jedna je od najboljih metoda ocjene bubrežne funkcije. Postoje oskudni podaci o procjeni glomerularne filtracije u djece i mladih odraslih oboljelih od hemofilije. Cilj našeg istraživanja je utvrditi razliku između tri često korištene metode za procjenu glomerularne filtracije u pedijatrijskoj populaciji u skupini pacijenata oboljelih od hemofilije. U naše prospektivno istraživanje uključili smo 36 djece s hemofilijom umjerenog ili teškog stupnja. Svakom pacijentu procijenjena je glomerularna filtracija koristeći jednostavnu, kreatinin baziranu jednadžbu po Schwartzu, cistatin C baziranu jednadžbu i kreatinin - cistatin C baziranu jednadžbu. Razlika između tri jednadžbe koristeći jednosmjerni ANOVA test bila je statistički značajna (p <0.001), a post hoc analiza pokazala je razliku između svake od navedenih metoda. Korelacijska analiza pokazala je najjače pozitivne korelacije između jednostavne jednadžbe po Schwartzu i kreatinin - cistatin C jednadžbe (r=0.866) promatrajući tri navedene jednadžbe. Korelacija između tri opisane jednadžbe za procjenu glomerularne filtracije postoji, ali sa značajnim neslaganjem. Zbog primijećenog neslaganja između procijenjene glomerularne filtracije u pacijenata s hemofilijom daljnja istraživanja su potrebna s ciljem pronalaska optimalne jednadžbe za procjenu glomerularne filtracije. Štoviše, preporučujemo uključivanje jednadžba za procjenu glomerularne filtracije u rutinsko praćenje djece oboljele od hemofilije

Complex Regional Pain Syndrome Type I after Diphtheria-Tetanus (Di-Te) Vaccination

Complex regional pain syndrome type I (CRPS I) is a disorder of one or more extremities characterized by pain, ab- normal sensitivity (allodynia), swelling, limited range of motion, vasomotor instability, fatigue and emotional distress. The symptoms may be aggravated by even minor activity or weather change. It is usually provoked by injury, surgery or injection but in a small proportion of patients CRPS I develops without a clear causative event. There are several litera- ture reports on CRPS after rubella and hepatitis B vaccination. We present a case of CRPS I affecting the left arm after diphtheria and tetanus (Di-Te) vaccination in the left deltoid muscle in a young girl having experienced profound emo- tional stress before the vaccination procedure. History data on previous minor trauma at the site of vaccination or emo- tional stress may necessitate temporary vaccination delay due to their proneness to impaired local or systemic immune response and CRPS as a complication of vaccination. If a child or an adult has prominent swelling and severe pain after vaccination, the diagnosis of CRPS I should be considered and if confirmed, the multidisciplinary treatment should start as soon as possible

CD20 Positive Childhood B-non Hodgkin Lymphoma (B-NHL): Morphology, Immunophenotype and a Novel Treatment Approach: A Single Center Experience

Lymphomas represent the third most common group of cancers in childhood and adolescence, mature B non Hodgkin’s lymphoma (B-NHL) accounting for up to 60% of newly diagnosed patients. The diagnosis of specific entities of B-NHL is based on well-defined morphologic analysis, immunophenotyping, cytogenetics and molecular genetics, which determine the optimal treatment strategy. In adult population a major turning point in treatment of B-NHL has been achieved since rituximab, in combination with CHOP has improved the survival rate up to 19%. Rituximab is a chimeric monoclonal antibody that targets CD20, a transmembrane calcium channel expressed on normal and malignant B-cells that mediates cytotoxic, apoptotic and anti-proliferative effects. The effect of rituximab in pediatric population is still not well enough investigated. Based on morphology and immunophenotype of malignant cells, seven children with B-NHL in our institution were eligible for treatment with modified B-NHL-Berlin-Frankfurt-Münster (BFM)-95-based protocol with rituximab administered on day -5. The complete remission was achieved in all seven patients. Six patients are still in complete remission at least 12 months after having finished chemotherapy and one patient relapsed two months after the last cycle and subsequently died. Major adverse effects observed during treatment were prolonged B-cell depletion and myelosupression. Rituximab in combination with B-NHL-BFM-95 protocol was otherwise well tolerated and proved to be effective in children and adolescents with B-NHL. The number of our patients is too small and the follow-up of a larger group of patients will help in defining the role of rituximab in the treatment of childhood B-NHL

Reevaluation of von Willebrand disease diagnosis in a Croatian paediatric cohort combining bleeding scores, phenotypic laboratory assays and next generation sequencing: a pilot study

This study reevaluated von Willebrand disease (vWD) diagnosis in a Croatian paediatric cohort by combining bleeding scores (BS), phenotypic laboratory testing, and next-generation sequencing (NGS). A total of 25 children (11 males and 14 females, median age 10 years, from 2 to 17) previously diagnosed with vWD were included. BS were calculated using an online bleeding assessment tool. Phenotypic laboratory analyses included platelet count, platelet function analyser closure times, prothrombin time, activated partial thromboplastin time, von Willebrand factor antigen (vWF:Ag), vWF gain-of-function mutant glycoprotein Ib binding activity (vWF:GPIbM), vWF collagen binding activity (vWF:CBA), factor VIII activity (FVIII:C) and multimeric analysis. Next-generation sequencing covered regions of both vWF and FVIII genes and was performed on MiSeq (Illumina, San Diego, USA). Disease-associated variants identified in 15 patients comprised 11 distinct heterozygous vWF gene variants in 13 patients and one novel FVIII gene variant (p.Glu2085Lys) in two male siblings. Four vWF variants were novel (p.Gln499Pro, p.Asp1277Tyr, p.Asp1277His, p.Lys1491Glu). Three patients without distinctive variants had vWF:GPIbM between 30 and 50%. Patients with identified vWF gene variants had statistically significant lower values of vWF:GPIbM (P = 0.002), vWF:Ag (P = 0.007), vWF:CBA (P < 0.001) and FVIII:C (P = 0.002), compared to those without. Correlations between BS and phenotypic laboratory test results were not statistically significant for either of the tests. The applied diagnostic approach confirmed the diagnosis of vWD in 13 patients and mild haemophilia A in two. Limited utility of BS in the paediatric population was evidenced

Zatajenje bubrega povezano s humanim BK poliomavirusom i humanim adenovirusom u djeteta s akutnom limfoblastičnom leukemijom

Immunocompromised patients are susceptible to multiple severe viral infections. This paper describes a 4-year-old boy with newly diagnosed B-cell precursor acute lymphoblastic leukaemia. The 4-year-old patient developed haemorrhagic cystitis, obstructive nephropathy and renal failure due to human polyomavirus BK and human adenovirus co-infection. Cidofovir should be used only in life-threatening cases.Imunokompromitirani su bolesnici podložni višestrukim teškim virusnim infekcijama. U radu opisujemo četverogodišnjeg dječaka s novodijagnosticiranom prekursorskom B-staničnom akutnom limfoblastičnom leukemijom koji je razvio hemoragijski cistitis, opstruktivnu nefropatiju i zatajenje bubrega nakon ko-infekcije humanim BK poliomavirusom i humanim adenovirusom. Cidofovir treba primjenjivati samo u slučajevima u kojima postoji životna opasnost

1,3-Β-D-glucan in invasive fungal infection diagnostics – first Croatian experience

Invazivne gljivne infekcije (IGI) važan su problem suvremene medicine. Razlog tomu jesu rastući broj imunokompromitiranih bolesnika te visoke stope morbiditeta i mortaliteta zbog ovih infekcija. Pravodobno postavljena dijagnoza IGI-ja od presudne je važnosti jer odgađanje primjene antifungalne terapije utječe na ishod liječenja bolesnika. Kultivacija kao konvencionalna dijagnostička metoda ima nisku osjetljivost, dugo traje i nalaže uzimanje invazivnog uzorka. Zbog toga se posljednjih dvadesetak godina radi ranije i osjetljivije dijagnostike istražuju i primjenjuju fungalni biomarkeri. 1,3-β-D-glukan (BDG) fungalni je biomarker odrediv u serumu bolesnika kojim se može dokazati prisutnost ovih gljivnih patogena: Candida spp., Aspergillus spp., Acremonium, Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporothrix schenckii, Saccharomyces cerevisiae i Pneumocystis jirovecii. Zbog niske razine odnosno nepostojanja BDG-a u staničnoj stijenci ovim se testom ne mogu dokazati vrste roda Cryptococcus spp. i reda Mucorales. Visoka negativna prediktivna vrijednost BDG-a u slučaju negativne vrijednosti može se iskoristiti za donošenje odluke o prekidu antifungalne terapije i biti dio strategije upravljanja primjenom antifungalnih lijekova u jedinicama intenzivnog liječenja. Kod hematoloških bolesnika BDG se može primjenjivati radi probira i u sklopu dijagnostičke obrade pri sumnji na IGI. Pouzdanost testa kod pojedinog bolesnika veća je u slučaju dvaju ili više uzastopno pozitivnih rezultata. Utjecaj antifungalne profilakse na rezultate testa BDG-a još je nejasan. Kinetiku BDG-a za sada je teško korelirati s kliničkim ishodom. Pedijatrijskim bolesnicima još nisu definirane granične vrijednosti za interpretaciju vrijednosti BDG-a iako su o tome objavljena brojna istraživanja. Trenutačno vrijedeće smjernice i dalje ne preporučuju primjenu ovoga fungalnog biomarkera kao rutinskoga dijagnostičkog testa u djece, premda može poslužiti u određenim situacijama uzimajući u obzir njegova ograničenja. BDG kao fungalni biomarker važan je napredak u dijagnostici IGI-ja te uz istodobnu primjenu ostalih dijagnostičkih metoda, ispravnu interpretaciju i racionalnu primjenu može pomoći ranijem i uspješnijem postavljanju dijagnoze i liječenju bolesnika s IGI jem.Invasive fungal infections (IFI) are an important problem of modern medicine. The reason is growing population of immunocompromised patients and high morbidity and mortality of these infections. Timely diagnosed IFI is of utmost importance because the delay of antifungal treatment has impact on treatment outcome. Cultivation as a conventional diagnostic method has low sensitivity, long duration and demands obtaining invasive samples. Therefore, in the last two decades fungal biomarkers are investigated for earlier and more sensitive diagnostics. 1,3-β-D-glucan (BDG) is a fungal biomarker in patients’ sera that enables detection of the following fungal pathogens: Candida spp., Aspergillus spp., Acremonium, Coccidioides immitis, Fusarium spp., Histoplasma capsulatum, Trichosporon spp., Sporotrix schenckii, Saccharomyces cerevisiae and Pneumocystis jirovecii. Low level and absence of BDG in the cell wall unables the detection of Cryptococcus spp. and order Mucorales with this test. High negative predictive value of BDG can be used when deciding to stop antifungal treatment and be a part of strategy for antifungal stewardship in intensive care units. In hematological patients BDG can be used as a screening method or as a part of diagnostic work-up when IFI is suspected. Reliability of test result is higher when two or more consecutive samples are positive. Influence of antifungal prophylaxis on BDG test results is still unclear. BDG kinetics and its relation to clinical outcome are still investigated. For pediatric population cut-off values for interpretation are still not defined, although many studies have been published investigating this issue. Although still not recommended by pediatric guidelines, this test can help in certain situations having in mind its limitations. BDG as a fungal marker represents the significant progress in IFI diagnostics. With simultaneous application of other diagnostic methods, exact interpretation and rational use, it can help earlier and more successful diagnostics and treatment of IFI

Subcutaneous Panniculitis-like T-cell Lymphoma in a 19 Month-old Boy: A Case Report

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare type of T-cell lymphoma of CD3+CD8+ phenotype characterized by deep-seated skin nodules or plaques mimicking panniculitis, a result of neoplastic lymphocytes infiltrating the subcutaneous fatty tissue. We present a case of a 19-month year old boy with SPTCL diagnosed and successfully treated in our institution. Disease first presented with symptoms of high fever and painful erythematous nodule located below the umbilicus. Later on the infiltrates appeared on the face, legs, arms and the back of the body. As the most decisive in obtaining the diagnosis, skin biopsy showed atypical, small to medium-sized lymphatic cells infiltrating the deeper dermal layers as well as the subcutaneous adipous tissue surrounding the adipocytes. Imunohystochemical analysis showed neoplastic lymphocytes positive for CD2, CD3, CD5, CD7, CD8, Tia-1, granzyme B and perforine, and negative for CD20, CD34, TDT and CD56. No infiltration of blood vessels or epidermis was evident. Specific T-cell lymphomas protocol (EURO-LB 02) was then initiated which resulted with rapid regression of all general and local symptoms. The treatment was completed according to schedule and the child is now, 24 months after the initiation of the treatment, in complete remission