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Traditionally the amount of fluid and electrolytes needed in intravenous fluid therapy in children has been calculated by using Holliday-Segar method published in 1957. By using Holliday-Segar method, the concentration of sodium in intravenous fluids is markedly less compering to plasma. Due to concern of risk for severe hyponatremia there is an increased use of isotonic intravenous fluid therapy that contians the same amount of sodium as plasma among acutely ill children. According to our clinical experience mild hyponatremia is common among acutely ill children, whereas severe hyponatremia (serum sodium less than 125 mmol/l) is rare though hypotonic intravenous fluid therapy was used in our clinic. The increasing use of isotonic intravenous fluid therapy among acutely ill children also increased use of commercially available plasma-like fluids, though there are only limited evidence of the use of plasma-like commercially available intravenous fluids in children. To get more evidence of the use of plasma-like isotonic fluid therapy in acutely ill children, we set up a randomized clinical trial. We compared traditionally used intravenous fluid therapy (G5% with 80 mmol/l of sodium and 20 mmol/l of potassium) to commercially available plasma-like isotonic fluid therapy (Plasmalyte glucose containing 140 mmol/l of sodium and 5 mmol/l of potassium). We also set up a retrospective register-based cohort study to evaluate the occurrence and risk factor for electrolyte abnormalities. 614 children were enrolled to randomized clinical trial. According to randomized clinical trial, the use of plasma-like isotonic fluid therapy caused an increased risk for electrolyte abnormalities (20% vs 2.9 %, 95% CI 12–22%), most notably for hypokalemia (19% vs 2.9%, 95 CI 11–21%). In randomized trial, the use of plasmalike isotonic fluid therapy did not decreas the risk for hyponatremia. However, in cohort study including 10-year period, 0.1% of children receiving hypotonic intra, Tiivistelmä Perinteisesti lasten neste- ja elektrolyyttitarve on laskettu vuonna 1957 julkaistun Holliday-Segarin metodin mukaisesti, jolloin suonensisäinen nestehoito sisältää vähemmän natriumia kuin plasma. Viime aikoina lapsipotilaiden nestehoidossa on siirrytty suosimaan aiemmin käytettyä nestehoitoa enemmän natriumia sisältävää nestettä, sillä perinteisen nestehoidon on ajateltu altistavan vaikean hyponatremian kehittymiselle. Aiempi kliininen kokemuksemme on, että äkillisesti sairastuneilla lapsipotilailla on usein lievä hyponatremiaa, mutta vaikea hyponatremia (natrium alle 125 mmol/l) on harvinainen myös perinteisen nestehoidon aikana. Uusien suonensisäisten nestehoitosuositusten myötä kaupallisten plasman kaltaisten valmisnesteiden käyttö lasten suonensisäisessä nestehoidossa on lisääntynyt, vaikka näyttö niiden hyödystä lapsipotilailla on rajallinen. Jotta saisimme lisää tietoa plasmankaltaisten valmisnesteiden käytöstä äkillisesti sairailla lapsilla, suunnittelimme satunnaistetun kliinisen tutkimuksen, jossa vertasimme perinteisempää nestehoitoa (G5%, jossa natriumia 80 mmol/l ja kaliumia 20 mmol/l) kaupalliseen, plasmankaltaiseen valmisnesteeseen (Plasmalyte glukoosi, natriumia 140 mmol/l ja kaliumia 5 mmol/l). Lisäksi selvitimme elektrolyyttihäiriöiden esiintyvyyttä- ja riskitekijöitä 10 vuoden retrospektiivisellä seurantatutkimuksella. Satunnaistettuun kliiniseen tutkimukseemme rekrytoitiin yhteensä 614 lasta. Tutkimuksemme perusteella elektrolyyttisisällöltään plasmantyyppisen valmisnesteen käyttö lisäsi elektrolyyttihäiriöiden ilmaantuvuutta verrattuna perinteisesti käytettyyn nestehoitoon (20 % vs 2.9 %, 95 % CI 12–22 %). Erityisesti plasmantyyppinen valmisneste altisti hypokalemian kehittymiselle (19 % vs 2.9 %, 95 % CI 11–21 %). Seurantatutkimuksessa havaitsimme, että vaikea hyponatremia on hyvin harvinainen äkillisesti sairastuneilla lapsipotilailla (0.2 %) kun taas lievä hyponatremia on yleinen (11.5 %). Satunnaistetussa kliinisessa tutkimuksess

Tiivistelmä Virtsatieinfektio on pienillä lapsilla yleisin sairaalahoitoon johtava bakteeritulehdus. Virtsankeräystyynyllä tai -pussilla saatu positiivinen tulos kannattaa yleensä varmistaa luotettavammalla menetelmällä. Lentovirtsan saamista imeväiseltä voi nopeuttaa sivelemällä alavatsaa kylmillä nestelapuilla. Hyvävointinen lapsi voidaan hoitaa suun kautta annosteltavilla lääkkeillä avoterveydenhuollossa. Virtsaelinten kaikututkimus on aiheellinen ainakin imeväisillä sekä ensimmäisen munuaistason tulehduksen jälkeen.

Importance: Although topical antibiotics are often prescribed for treating acute infective conjunctivitis in children, their efficacy is uncertain. Objective: To assess the efficacy of topical antibiotic therapy for acute infective conjunctivitis. Design, Setting, and Participants: A randomized clinical trial was conducted in primary health care in Oulu, Finland, from October 15, 2014, to February 7, 2020. Children aged 6 months to 7 years with acute infective conjunctivitis were eligible for enrollment. The participants were followed up for 14 days. A subsequent meta-analysis included the present trial and 3 previous randomized clinical trials enrolling pediatric patients aged 1 month to 18 years with acute infective conjunctivitis. Interventions: Participants in the present randomized clinical trial were randomized to moxifloxacin eye drops, placebo eye drops, or no intervention. Main Outcomes and Measures: The primary outcome in the present randomized clinical trial was time to clinical cure (in days); in the meta-analysis, the primary outcome was the proportion of participants with conjunctival symptoms on days 3 to 6. Results: The randomized clinical trial included 88 participants (46 [52%] girls), of whom 30 were randomized to moxifloxacin eye drops (mean [SD] age, 2.8 [1.6] years), 27 to placebo eye drops (mean [SD], age 3.0 [1.3] years), and 31 to no intervention (mean [SD] age, 3.2 [1.8] years). The time to clinical cure was significantly shorter in the moxifloxacin eye drop group than in the no intervention group (3.8 vs 5.7 days; difference, −1.9 days; 95% CI, −3.7 to −0.1 days; P = .04), while in the survival analysis both moxifloxacin and placebo eye drops significantly shortened the time to clinical cure relative to no intervention. In the meta-analysis, a total of 584 children were randomized (300 to topical antibiotics and 284 to a placebo), and the use of topical antibiotics was associated with a significant reduction in the proportion of c

Aim: The aim was to evaluate the incidence, hospitalisations and deaths in acutely ill children with dysnatraemias. Methods: This was a register-based cohort study of 46 518 acutely ill children aged <16 years who visited a paediatric emergency department. Risk factors were assessed using two nested case–control studies. Results: Moderate to severe hypernatraemia occurred in 92 children (0.20%; 95% confidence interval [CI]: 0.16%–0.24%) and moderate to severe hyponatraemia in 131 children (0.28%; 95% CI: 0.24%–0.33%). Underlying medical conditions increased the risk of both moderate to severe hypernatraemia (odds ratio [OR]: 17; 95% 5.5–51) and moderate to severe hyponatraemia (OR: 3.5; 95% CI: 2.0–5.9). The use of a feeding tube (OR: 14; 95% CI: 3.2–66) and intellectual disability (OR: 7.3; 95% CI: 3.0–18) was associated with moderate to severe hypernatraemia. The risk of death was associated with moderate to severe hypernatraemia (OR: 19; 95% CI: 2.0–2564) and moderate to severe hyponatraemia (OR: 33; 95% CI: 3.7–4311). Conclusions: Severe dysnatraemias were more prevalent in acutely ill children with underlying medical conditions and were markedly associated with the risk for death.

Importance: Limited data are available on the clinical impact of multiplex polymerase chain reaction (PCR) point-of-care testing for respiratory pathogens in acutely ill children. Objective: To evaluate the effect of multiplex PCR point-of-care testing for respiratory pathogens on antibiotic use in acutely ill children. Design, Setting, and Participants: This unblinded, randomized clinical trial was conducted from May 6, 2019, through March 12, 2020. The participants were followed up until hospitalization or discharge from the emergency department (ED) for primary outcome. The study was conducted at the pediatric ED of Oulu University Hospital, Finland. Eligible study participants were children aged 0 to 17 years with fever and/or any respiratory signs or symptoms. Children with underlying medical conditions were included. The statistical analyses were performed between August 11, 2020, and September 14, 2021. Interventions: The participants were randomly assigned in a 2:1 ratio either to undergo multiplex PCR point-of-care testing (18 respiratory viruses and 3 bacteria with results ready within 70 minutes) upon arrival at the ED or to receive routine care. Main Outcomes and Measures: The primary outcome was the proportion of children receiving antibiotic therapy. The secondary outcomes were the numbers of diagnostic tests and radiographic imaging procedures performed and costs. Results: A total of 1417 children were assessed for eligibility. After exclusions, 1243 children (692 boys [56%]) were randomly allocated to either the intervention (829 children) or control (414 children) group. The mean (SD) age of the participants was 3.0 (3.6) years in the intervention group (median [IQR], 1.7 [0.4–4.1] years) and 3.0 (3.5) years (median [IQR], 1.9 [0.4–4.1] years) in the control group. Multiplex PCR point-of-care testing for respiratory pathogens did not reduce the overall prescribing of antibiotics in the emergency department (226 children [27.3%] in the inter

Background: Hypotonic fluids have been associated with hospital-acquired hyponatremia. The incidence of life-threatening severe hyponatremia associated with hypotonic fluids has not been evaluated. Methods: This was a population-based cohort study of 46,518 acutely ill children 15 years of age or under who visited the pediatric emergency department (ED) at Oulu University Hospital, Finland, between 2007 and 2017. We retrieved all electrolyte measurements from the comprehensive electronic laboratory system and reviewed medical records for all patients with severe hyponatremia. Results: The overall occurrence of severe hyponatremia (serum sodium < 125 mmol/L) was found in 27 out of 46,518 acutely ill children (0.06%, 95% confidence interval 0.04–0.08%). After admission, severe hyponatremia developed in seven of 6,984 children receiving moderately hypotonic fluid therapy (0.1%, 95% confidence interval 0.04–0.2%), usually within 8 h of admission. All children who developed severe hyponatremia during hospitalization were severely ill. Conclusion: In this register-based cohort study of children presenting to the ED, severe hyponatremia developed in one of 998 acutely ill children receiving moderately hypotonic fluid therapy.

Tiivistelmä Hemofagosyyttinen lymfohistiosytoosi (HLH) on henkeä uhkaava tulehdusreaktio, jonka syntymekanismina on T-imusolujen ja makrofagien keskinäinen sytokiinivälitteinen aktivaatio. Taudin tunnusmerkkejä ovat epäselvä ja pitkittynyt kuume, maksan ja pernan suurentuminen sekä verenkuvan solupuutokset. Perinnöllinen HLH (FHL) on ryhmä geneettisiä sairauksia, joissa tauti kehittyy ensimmäisten elinkuukausien aikana muutoin terveelle lapselle. FHL johtuu sytotoksisten imusolujen kyvyttömyydestä tuhota tulehdusvasteen herättäneet antigeeniä esittelevät solut, mistä seuraa sytokiinivälitteinen itseään voimistava tulehdusreaktio. FHL:n hoito perustuu T-solujen tukahduttamiseen ja allogeeniseen kantasolusiirtoon. FHL on harvinainen mutta merkittävä erotusdiagnostinen vaihtoehto, kun kuumeisen imeväisen verenkuvassa havaitaan solupuutoksia. Taudin nopea tunnistaminen on tärkeää, jotta tehokas hoito päästään aloittamaan ennen monielinvauriota.

Background: Homozygous loss of DIAPH1 results in seizures, cortical blindness, and microcephaly syndrome (SCBMS). We studied 5 Finnish and 2 Omani patients with loss of DIAPH1 presenting with SCBMS, mitochondrial dysfunction, and immunodeficiency. Objective: We sought to further characterize phenotypes and disease mechanisms associated with loss of DIAPH1. Methods: Exome sequencing, genotyping and haplotype analysis, B- and T-cell phenotyping, in vitro lymphocyte stimulation assays, analyses of mitochondrial function, immunofluorescence staining for cytoskeletal proteins and mitochondria, and CRISPR-Cas9 DIAPH1 knockout in heathy donor PBMCs were used. Results: Genetic analyses found all Finnish patients homozygous for a rare DIAPH1 splice-variant (NM_005219:c.684+1G>A) enriched in the Finnish population, and Omani patients homozygous for a previously described pathogenic DIAPH1 frameshift-variant (NM_005219:c.2769delT;p.F923fs). In addition to microcephaly, epilepsy, and cortical blindness characteristic to SCBMS, the patients presented with infection susceptibility due to defective lymphocyte maturation and 3 patients developed B-cell lymphoma. Patients’ immunophenotype was characterized by poor lymphocyte activation and proliferation, defective B-cell maturation, and lack of naive T cells. CRISPR-Cas9 knockout of DIAPH1 in PBMCs from healthy donors replicated the T-cell activation defect. Patient-derived peripheral blood T cells exhibited impaired adhesion and inefficient microtubule-organizing center repositioning to the immunologic synapse. The clinical symptoms and laboratory tests also suggested mitochondrial dysfunction. Experiments with immortalized, patient-derived fibroblasts indicated that DIAPH1 affects the amount of complex IV of the mitochondrial respiratory chain. Conclusions: Our data demonstrate that individuals with SCBMS can have combined immune deficiency and implicate defective cytoskeletal organization and mitochondrial dysfunction in

Background: Symptomatic primary Epstein-Barr virus infection is a usually self-limiting illness in adolescents. We present a case of an adolescent who had been receiving azathioprine for inflammatory bowel disease for four years and developed a life-threatening primary Epstein-Barr virus infection successfully treated with rituximab. Case presentation: An 11-year-old girl presented with chronic, bloody diarrhea. Endoscopic biopsies confirmed a diagnosis of chronic ulcerative colitis with features of Crohn’s disease. Azathioprine was initiated after one year due to active colitis. She responded well and remission was achieved. At the age of 16 years she developed a life-threatening Epstein-Barr virus infection including severe multiple organ failure and was critically ill for 4 weeks in the intensive care unit. Natural killer cells were virtually absent in the lymphocyte subset analysis. Azathioprine was stopped on admission. She was initially treated with corticosteroids, acyclovir and intravenous immunoglobulin. Approximately 30 days after admission, she developed signs of severe hepatitis and pneumonitis and received weekly rituximab infusions for 8 weeks. Primary immunodeficiency was excluded by whole exome sequencing in two independent laboratories. Persistent viremia stopped when the natural killer cell count started to rise, approximately 90 days after the cessation of azathioprine. Conclusions: We found 17 comparable cases in the literature. None of the previous cases reported in the literature, who had been treated with azathioprine and developed either a severe or a fatal Epstein-Barr virus infection, underwent full genetic and prospective immunological workup to rule out known primary immunodeficiencies. Recently, azathioprine has been shown to cause rather specific immunosuppression, resulting in natural killer cell depletion. Our case demonstrates that slow recovery from azathioprine-induced natural killer cell depletion, 3 months after the stop

Around 3% of pregnant women in Finland have genital Chlamydia trachomatis infection, which can be transmitted from mother to newborn at birth. The risk of transmission has been reported to be 10–70% in vaginal deliveries resulting in conjunctivitis in 10–30% of cases and lower respiratory tract infection in 0–20% of cases. Although usually benign, Chlamydia trachomatis infections in infancy may result in long-term consequences, including conjunctival and corneal scarring, chronic cough and abnormal lung function. Based on the transmission rates published in prior studies, chlamydial conjunctivitis should occur in approximately 200 infants and chlamydial lower respiratory tract infection in 100 infants each year in our country, but in clinical practice we rarely encounter or diagnose infants with Chlamydia trachomatis infections. To investigate the reason for this discrepancy and to improve the recognition of Chlamydia trachomatis-infected infants, we set out to study the risk of vertical transmission of Chlamydia trachomatis in a population-based setting, to describe the typical features of Chlamydia trachomatis infections in infants and to evaluate the occurrence of Chlamydia trachomatis in both neonatal conjunctivitis and lower respiratory tract infections in infants. When studying the probability of vertical transmission of Chlamydia trachomatis a search through two national health registers for 1996–2011 yielded 206 children aged less than four years with a possible Chlamydia trachomatis infection. In a cohort of 933 823 births this represented an occurrence of 0.22 per 1000 live births (95% confidence interval 0.19–0.25). The risk of vertical transmission of Chlamydia trachomatis leading to a symptomatic infection in infancy was 0.8–1.8%. A review of patient charts to evaluate the typical features of Chlamydia trachomatis infections in infants (124/206) revealed that one-third of the infants with chlamydial conjunctivitis (33/124) had spontaneous blood, Tiivistelmä Noin 3 %:lla suomalaisista raskaana olevista naisista on klamydian (Chlamydia trachomatis) aiheuttama sukupuolitauti, joka voi tarttua äidistä lapseen synnytyksessä. Tartuntariskin on raportoitu olevan alatiesynnytyksessä noin 10–70 %. Noin 10–30 % tartunnan saaneista lapsista sairastuu silmätulehdukseen ja 0–20 % keuhkokuumeeseen. Vaikka imeväisten klamydiainfektiot ovat useimmiten lieviä tauteja, imeväisiällä sairastettu klamydiainfektio voi aiheuttaa silmän side- ja sarveiskalvon arpeutumista, pitkittynyttä yskää ja keuhkofunktion alenemaa. Aiempien tutkimusten perusteella arvioimme, että Suomessa sairastuu vuosittain noin 200 imeväistä klamydian aiheuttamaan silmätulehdukseen ja noin 100 imeväistä klamydiakeuhkokuumeeseen. Kliininen kokemuksemme on kuitenkin, että kohtaamme klamydiaa sairastavia imeväisiä varsin harvoin. Tämän ongelman ratkaisemiseksi ja klamydiaa sairastavien imeväisten paremmaksi tunnistamiseksi suunnittelimme tutkimuksen, jonka tarkoituksena on selvittää väestöpohjainen riski klamydian tarttumiselle äidistä vastasyntyneeseen, kuvata imeväisten klamydiainfektioiden tyypilliset piirteet sekä selvittää klamydian osuus imeväisten silmätulehduksissa ja alle kuuden kuukauden ikäisten imeväisten alahengitystieinfektioissa. Klamydian sairastaneet lapset poimittiin kahdesta suomalaisesta terveydenhuoltorekisteristä vuosina 1996–2011. Tuona aikana 206 lasta oli sairastanut mahdollisen klamydiainfektion, joten klamydian ilmaantuvuus oli 0,22/1000:tta elävänä syntynyttä kohti (95 % luottamusväli 0,19–0,25). Väestöpohjainen riski äidin sukupuoliklamydian tarttumiselle vastasyntyneeseen niin että lapselle aiheutuu oireinen infektio oli 0,8–1,8 %. Saatavilla olevien potilasasiakirjojen (124/206) perusteella kolmasosalla (33/124) imeväisistä, jotka sairastivat klamydian aiheuttamaa silmätulehdusta, oli oireena spontaani verinen kyynel- tai rähmäerite. Klamydiakeuhkokuumetta sairastavista puolella (15/32) esiintyi hengityksen vinkumista, mutta kla