Viral Infections, Including Influenza and Corona Virus Disease 2019, and Vitamin D: A Mini-Review

Recent research about the influence of vitamin D (VD) deficiency on the occurrence of viral infections suggests that children with VD deficiency have attenuated immune response. This, in turn, increases the severity of viral infections, especially those of the respiratory tract, that show a typical seasonality pattern during the winter months. Despite the immunization of children at the global level, outbreaks of influenza do frequently occur. Over the past months, we have witnessed that the explosive pandemic of the corona virus disease 2019 (COVID-19) has caused significant mortality in some countries. Numerous studies have shown that VD deficiency is increasingly prevalent worldwide, and that it is potentially associated with the onset of viral infections. Persons with hypovitaminosis D and subsequent secondary immunodeficiencies ought to be identified and treated, while preventive supplementation of VD should be recommended to the general population to avoid VD deficiency during the winter. In this way, the burden of viral infections on population health and economy could be reduced. This paper also reviews the influence of VD on infections caused by hepatitis B and C viruses, human papillomavirus, Epstein–Barr virus, Human herpes virus 6, herpes simplex virus, and human immunodeficiency virus

Objavljena knjiga «Sideropenična anemija »

Sideropenična anemija je jedna od najčešćih bolesti dječje dobi, a javlja se i u odrasloj populaciji. Procjenjuje se da u svijetu boluje od nedostatka željeza oko 2 milijarde ljudi. Više od 30% trudnica u nerazvijenim zemljama ima nedostatak željeza, a očekujemo da će jedno od 4-5 novorođenčadi razviti sideropeniju. Prisutnost željeza je neophodna za razvoj djeteta, a njegov nedostatak naročito u fetalno doba i u prve dvije godine života može ostaviti teške posljedice na različite organske sustave. Najviše strada središnji živčani sustav i imunosni sustav, pa takva djece mogu imati teške posljedice na rast i razvoj

Objavljena knjiga «Sideropenična anemija »

Sideropenična anemija je jedna od najčešćih bolesti dječje dobi, a javlja se i u odrasloj populaciji. Procjenjuje se da u svijetu boluje od nedostatka željeza oko 2 milijarde ljudi. Više od 30% trudnica u nerazvijenim zemljama ima nedostatak željeza, a očekujemo da će jedno od 4-5 novorođenčadi razviti sideropeniju. Prisutnost željeza je neophodna za razvoj djeteta, a njegov nedostatak naročito u fetalno doba i u prve dvije godine života može ostaviti teške posljedice na različite organske sustave. Najviše strada središnji živčani sustav i imunosni sustav, pa takva djece mogu imati teške posljedice na rast i razvoj

Pneumokokno povezani hemolitsko-uremički sindrom nakon invazivne pneumokokne bolesti kod dvogodišnje djevojčice

The haemolytic uremic syndrome is characterized by microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure and is the most common in children under the age of 4. The etiology can be associated with some infectious agents like Streptococcus pneumoniae. We review the case of a 2-year-old girl presenting with invasive pneumococcal disease followed by the haemolytic uremic syndrome. The onset of the haemolytic uremic syndrome clinical manifestation was preceded by un upper respiratory tract infection. The physical finding was in extremely bad condition with pallor. She was adinamic, confused, dispnoic, dehydrated with peripheral circulatory failure. Tubular breath sounds with moist rales on both sides of the lung were registered as well as liver and spleen enlargement. Presenting clinical and laboratory data we confirmed that, in our case, following the invasive pneumococcal disease (pleuropneumonia, sepsis and septic shock), Streptococcus pneumoniae was the trigger of HUS. High doses of corticosteroids, fresh frozen plasma, antibiotics, and intravenous immunoglobulins were a successful treatment.Hemoliticko-uremicki sindrom karakterizira mikroangiopatska hemoliticka anemija, trombocitopenija i akutno zatajenje bubrega. Najcešce se javlja u djece u dobi mladoj od 4 godine. Etiologija je povezana s nekim infektološkim agensima kao što je Streptococcus pneumoniae. Prikazali smo slucaj dvogodišnje djevojcice s invazivnom pneumokoknom bolesti s hemoliticko-uremickim sindromom. Bolest je pocela infekcijom gornjeg respiratornog trakta. Djevojcica je primljena u vrlo teškom stanju, ekstremno blijeda, adinamicna, konfuzna, dispnoicna, dehidrirana u kolapsu periferne cirkulacije. Obostrano nad plucima culi su se brojni bronhiticki hropci, a jetra i slezena su bile uvecane. Klinicki i laboratorijski potvrdili smo da je u djevojcice pneumokokna invazivna bolest (pleuropneumonija, sepsa i septicki šok) uzrokovana Streptokokom pneumonije potaknula nastanak hemoliticko-uremickog sindroma. Uspješno izljecenje postignuto je primjenom visokih doza kortikosteroida, svježe smrznute plazme, antibiotika i intravenoznih imunoglobulina

Relationship Between Tumor Vascularity and Vascular Endothelial Growth Factor as Prognostic Factors for Patients with Neuroblastoma

Although the role of angiogenesis in tumor progression and response to treatment is generally well-characterized, for neuroblastomas clinical data regarding the contribution of angiogenesis and its predictive capacity remain unclear. The aim of this study was to evaluate whether tumor vascularity in the combination with expression of vascular endothelial growth factor (VEGF) represent prognostic factors for patients with neuroblastoma. Immunohistochemistry using anti- -CD34 and anti-VEGF antibodies was used to analyze paraffin-embedded primary tumor tissues from 56 patients diagnosed with neuroblastoma. Tumor vascularity was estimated by calculating the tumor vascular volume fraction (TVVF), and VEGF expression was determined using semi-quantitative scoring. Statistical analyses including multivariate analysis were performed and compared with these two factors. Tumor vascularity had impact on survival of high VEGF expression neuroblastoma patients. Combination of high VEGF expression and TVVF value 5% was independent predictor of overall survival (p-value =0.0041, odds ratio (OR) (95%CI)=8.67 (1.99–37.69) by the Cox proportional hazards model). This study revealed for the first time a group of extremely high-risk neuroblastoma with both high VEGF expression and poor vascularity. For these patients reduced rates of survival were observed (37% vs. 92.5%) (p<0.0001). These patients did not experience a significant improvement following hematopoietic stem cell transplantation, and could be candidates for receiving novel therapies. These results indicate the importance of the mutual relationship between tumor vascularity and VEGF, because it gives better insight into the prognosis of patients with neuroblastoma

Successful treatment with rituximab in boy with Evans syndrome - case report

Autoimuna hemolitička anemija (AIHA) je bolest uzrokovana nastankom protutijela usmjerenih protiv antigena na površini vlastitih eritrocita. Ovisno o termalnim obilježjima, autoprotutijela se dijele na: hemolitičke anemije uzrokovane “toplim” i “hladnim” protutijelima. AIHA-i mogu biti primarni i sekundarni. Sekundarni AIHA-i su udruženi s nekom drugom bolešću poput sistemskog lupusa eritematodesa, imunodefi cijencije ili limfoproliferativog poremećaja. Osnovno obilježje AIHA-a je pozitivan direktni Coombsov test koji otkriva protutijela klase IgG i dijelove komplementa (najčešće anti- C3) vezane na površinu eritrocita. Evansov sindrom je istodobna ili uzastopna pojava AIHA-a s pozitivnim direktnim Coombsovim testom i imune trombocitopenije (ITP). U radu smo prika zali dvogodišnjeg dječaka u kojeg je u dobi od 10 mjeseci dijagnosticiran AIHA rekurentnog tijeka. U dobi od 17 mjeseci uz osnovnu bolest otkriven je i ITP te je postavljena dijagnoza Evansovog sindroma. Dječak je liječen glukokortikoidima, pripravkom humanih imunoglobulina, transfuzijama deplazmatiziranih eritrocita i koncentratom trombocita u više navrata, ali bez remisije bolesti. Naposljetku, primjenom rituksimaba postignuto je kliničko poboljšanje i višemjesečna remisija bolesti.Autoimmune haemolytic anaemia (AIHA) is caused by production of antibodies against antigens on the surface of the red blood cells. It can be classifi ed as haemolytic anaemia due to warm and cold reactive antibodies and divided into primary and secondary AIHA (associated with an underlying disease: systemic lupus erythematodes, immunodefi ciency, lymphoproliferative disorders). The main feature of this anaemia is positive direct Coombs test which demonstrates antibodies of IgG class and complement (mostly anti-C3) on the surface of the red blood cells. Evans syndrome is the presence of simultaneous or sequential direct Coombs-positive AIHA in conjunction with immune thrombocytopenia (ITP). We report on a 2-year-old boy with diagnosed AIHA at age of 10 months with a repetitive course. At age of 17 months concomitant ITP occurs and diagnosis of Evans syndrome was made. The patient was treated with glucocorticoids, human immunoglobulins, red blood cells and platelet transfusions many times, without the stabile remission. Finally, treatment with rituximab was followed by clinical improvement and disease remission lasting for months

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

Schonlein-Henoch Syndrome in children and adolescents: epidemiologic data and coagulation disturbances

Svrha istraživanja bila je ispitati funkcionalnost trombocita u djece i adolescenata koji su bolovali od Schönlein-Henoch sindroma (SHS) u sklopu kojega se mogu pojaviti pojačana krvarenja, uz normalan broj trombocita, te prikazati epidemiološke podatke za istu populaciju. Najčešća mjesta manifestacije bolesti bila su koža i zglobovi. Bolest je bila najčešća u djece starosti između 7 i 20 godina, češća u djevojčica nego u dječaka. Najčešći poremećaj fiziološke aktivnosti trombocita bio je blokada otpuštanja endogenog ADP-a u slučaju kada je kao indukcijski agens bio upotrijebljen ADP. Štoviše, u 6 je pacijenata pokazana istovremena dezagregacija trombocita. Očito je da je pojačano krvarenje u sklopu SHS uzrokovano smanjenom funkcionalnom sposobnošću trombocita.The aim of the study was to examine the function of platelets in children and adolescents with Schönlein-Henoch Syndrome (SHS) presenting normal platelet count, and epidemiologic data. The most frequent SHS localization was the skin and joints. The most consistent defect in latelet aggregation was a block of the release of endogenous ADP when ADP was used as induction agent. In conclusion, our epidemiological data differ slightly from those observed by other authors. However, we have shown that increased tendency toward bleeding in SHS might be caused by function disturbances of platelets

Smjernice za prevenciju hemoragijske bolesti novorođenčeta - krvarenja nastalog zbog nedostatka vitamina K

Sažetak. Cili. Aktualizirati prevenciju hemoragijske.bolesti novorođendeta (HBN) ili krvarenja nastalog zbog nedostatka vitamina K u dojenačkom razdoblju sukladno novijim preporukama i praksi u svijetu. Materijal i metode. Već više od 50 godina Američka pedijatrijska akademija preporučuje intramuskulamu primjenu 0,5 mg do 1,0 mg vitamina Kl u novorođenadkom razdoblju, što je ponovila u svome najriovijem stajalištu od 2003. godine. U Hrvatskoj se navedena profilaksa sustavno provodi od 1994. godine nakon preporuka ad hoc skupine strudnjaka Hrvatskog pedijatrijskog društva i Hrvatskog društva za periratalnu medicinu Hrvatskog lijedničkog zbora. U međuvremenu je ustanovljeno da jednokratna intramuskulama (im.) primjena vitamina Kl u novorođenačkom razdoblju ne štiti isključivo dojenu djecu od kasnog oblika hemoragijske bolesti novorodendeta (najčešće od 2. do 13. tjedna života),koja se u većine dojenčadi manifestira kao intrakranijalno krvarenje koje može biti fatalno ili dovesti do teških neurorazvojnih posljedica. Osim toga neki roditelji su zabrinuti zbog mogućih komplikacija primjene im. injekcije, a stručna javnost se je uznemirila nakon retrospektivnog istraživanja kojim je postavljena sumnja na povezanost izmedu primjene im. injekcije vitamina Kl i pojave leukoza i drugih malignoma u djece u dobi od 6 godina, koje je kasnije opovrgnuto. U nekim je zemljama dokazano da se peroralnom (po.) primjenom malih dnevnih doza vitamina K1 od 2. do 13. tjedna u isključivo dojene djece može značajno smanjiti učestalost kasnog oblika HBN. Sličan učinak je postignut i po. primjenom 1 mg vitamina K1 od 2. do 13. tjedna, ali su protivnici te metode prigovarali zbog prekomjemo visokih koncentracija vitamina K1 u plazmi dojendadi nakon primjene jednokratne visoke doze. Uz niske dnevne doze vitamina K u nekim se zemljama primjenjuje u istom razdoblju i vitamin D 3 u dozi od 400 IJ sukladno preporukama Ameridke pedijatrijske akademije. Zakljuiak. U Hrvatskoj bi postojeće preporuke trebalo prilagoditi najnovijim preporukama prema kojima neposredno nakon rođenja sva novorodende treba dobiti 0,5 mg do 1,0 mg vitamina Kl im. i nakon toga isključivo dojena i rizična novorođenčad od 8. dana do 13. tjedna života po. 25ltgldan vitamina K1 i 400 IJ vitamina D 3