BackgroundSerum levels of N–terminal proB–type natriuretic peptide (NT–proBNP) are elevated in patients acute respiratory distress syndrome (ARDS). Recent studies showed a lower incidence of acute cor pulmonale in ARDS patients ventilated with lower tidal volumes. Consequently, serum levels of NT–proBNP may be lower in these patients.We investigated the relation between serum levels of NT–proBNP and tidal volumes in critically ill patients without ARDS at the onset of mechanical ventilation.MethodsSecondary analysis of a randomized controlled trial of lower versus conventional tidal volumes in patients without ARDS. NT–pro BNP were measured in stored serum samples. Serial serum levels of NT–pro BNP were analyzed controlling for acute kidney injury, cumulative fluid balance and presence of brain injury. The primary outcome was the effect of tidal volume size on serum levels of NT–proBNP. Secondary outcome was the association with development of ARDS.ResultsSamples from 150 patients were analyzed. No relation was found between serum levels of NT–pro BNP and tidal volume size. However, NT-proBNP levels were increasing in patients who developed ARDS. In addition, higher levels were observed in patients with acute kidney injury, and in patients with a more positive cumulative fluid balance.ConclusionSerum levels of NT–proBNP are independent of tidal volume size, but are increasing in patients who develop ARDS.

Fucosylation is essential for intercellular and intracellular recognition, cell-cell interaction, fertilization, and inflammatory processes. Only five types of congenital disorders of glycosylation (CDG) related to an impaired fucosylation have been described to date: FUT8-CDG, FCSK-CDG, POFUT1-CDG SLC35C1-CDG, and the only recently described GFUS-CDG. This review summarizes the clinical findings of all hitherto known 25 patients affected with those defects with regard to their pathophysiology and genotype. In addition, we describe five new patients with novel variants in the SLC35C1 gene. Furthermore, we discuss the efficacy of fucose therapy approaches within the different defects.

Background Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare rapidly progressive neurodegenerative disorder, resulting in early death. Intracerebroventricular enzyme replacement therapy (ERT) with cerliponase alfa is now available and has shown to delay disease progression in symptomatic patients. It is yet unknown if cerliponase alfa can prevent disease onset in presymptomatic patients. Results We evaluated the effect of 2 years of intracerebroventricular ERT in two siblings with CLN2 disease, one symptomatic (age 47 months) and one presymptomatic (age 23 months) at treatment start, using the CLN2 Clinical Rating Scale (CLN2 CRS), Gross Motor Function Measure-66 (GMFM-66) for motor function, Bayley Scales of Infant and Toddler Development, 3rd Edition, Dutch (BSID-III-NL) for neurocognitive development, brain MRI, and visual evoked potentials (VEP), electroretinogram (ERG) and retinoscopy for visual function. On the CLN2 CRS patient 1 showed a decline from 3 to 2 in the combined motor and language score due to regression in language use (CLN2 CRS total score after 2 years of treatment: 8), whereas a decline of 2 or more points in the combined motor and language score would be expected without treatment. Patient 2 retained the maximum score of 3 in all 4 subdomains (CLN2 CRS total score after 2 years of treatment: 12). The GMFM-66 total score declined from 46 to 39 in patient 1 and showed an age-appropriate increase from 66 to 84 in patient 2. Cognitive-developmental age decreased from 24 to 11 months in patient 1, whereas an increase in cognitive-developmental age from 21 to 39 months was seen in patient 2. Cerebral and cerebellar atrophy observed on MRI in patient 1 at age 42 months (before treatment) was not observed in patient 2 at age 48 months (after 2 years of treatment). Conclusion We show that cerliponase alfa is able to delay the onset of symptoms when treatment is started in a presymptomatic stage of CLN2 disease. Our results advocate the start of treatment at an early age before symptom onset, but should be confirmed in a larger cohort study.

Key Clinical MessageA general practitioner faces regularly soft tissue swelling in otherwise healthy children. Delay in diagnosis of soft tissue malignancies is often due to asymptomatic nature and the unfamiliarity with the age‐dependent differential diagnosis. Hence, an accurate knowledge is important to prevent important delay in diagnosis of potential malignancies.

Conclusions | METHODS | Patients | RESULTS | Clinical presentationAsshowninTable1,medianageofthechildrenatdiagnosiswas6.7 | Laboratory findingsAllpatientshadabiochemicalandhaematologicalwork-up,including sedimentationrate,bloodcellcount,kidneyandliverfunctiontests, which were normal in all patients. All patients tested negatively for the classical tumour markers β-HCG and α-fetoprotein in blood and sixtestednegativelyinthecerebrospinalfluid. | Pituitary function | Autoimmunity parameters | MRI findingsAt presentation, all patients had a thickening of the pituitary stalk | Other complementary examinationsSix patients had cerebrospinal fluid examination and a chest X-ray, fivepatientshadawholeskeletalX-raysurvey,andonepatienthad abonescintigraphy.Alltheseexaminationswerenormal.Nopatient underwentastalkbiopsy. | TreatmentAllpatientsreceiveddesmopressinfromthediagnosisofCDI.Thepatientwithcentralhypothyroidismwastreatedwiththyroxinsupplementationandreceivedduring8weeksoralglucocorticoids,starting 4weeksafterdiagnosis,asanevolvinganteriorpituitaryinsufficiency was expected, given an initial increase in ST. None of the patients received surgical or any other medical treatment at diagnosis or at laterstage. | OutcomeFollow-updataforatleast18monthswereavailableforallpatients.Allpatientswerekeptundercloseclinical (3monthlyinthefirstyear) andMRI (6monthlyinthefirst2years) A limitation of our study is the retrospective study design. All children underwent different hormonal and biological testing at different moments in the follow-up, and in particular, the autoimmune parameterswereonlytestedinalimitedgroupofchildren Clin Endocrinol.2006;65:470-478. 4. Leger J,Velasquez A, Garel C, Hassan M, Czernichow P. Thickened pituitarystalkonmagneticresonanceimaginginchildrenwithcentral diabetesinsipidus.J Clin Endocrinol Metab.1999;84:1954-1960. 5. DiIorgiN,AllegriAE,NapoliF,etal.Centraldiabetesinsipidusinchildrenandyoungadults:etiologicaldiagnosisandlong-termoutcome ofidiopathiccases.J Clin Endocrinol Metab.201499:1264-1272. 6. HayashiY,OishiM,KitaD,WatanabeT,TachibanaO,HamadaJ.Pure lymphocyticinfundibuloneurohypophysitiscausedbytheruptureof rathke'scleftcyst:reportof2casesandreviewoftheliterature.Turk Neurosurg.201525:332-336