The human cathelicidin hCAP-18 in serum of children with haemato-oncological diseases

The human cathelicidin hCAP-18 (pro-LL-37) is the pro-protein of the antimicrobial peptide LL-37. hCAP-18 can be produced by many different cell types; bone marrow neutrophil precursors are the main source of hCAP-18 in the circulation. Neutrophil count is used as a marker for myelopoiesis but does not always reflect neutrophil production in the bone marrow, and thus additional markers are needed. In this study, we established the reference interval of serum hCAP-18 level in healthy children and compared serum hCAP-18 levels between different diagnostic groups of children with haemato-oncological diseases, at diagnosis. We found that children with diseases that impair myelopoiesis, such as acute leukaemia, aplastic anaemia, or myelodysplastic syndrome, presented with low hCAP-18 levels, whereas patients with non-haematological malignancies displayed serum hCAP-18 levels in the same range as healthy children. Children with chronic myeloid leukaemia presented with high circulating levels of hCAP-18, probably reflecting the high number of all differentiation stages of myeloid cells. We suggest that analysis of serum hCAP-18 provides additional information regarding myelopoiesis in children with haemato-oncological diseases, which may have future implications in assessment of myelopoiesis in clinical management.Peer reviewe

Biomarkers for CNS injury in CSF are elevated in COVID-19 and associated with neurological symptoms and disease severity

BACKGROUND: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19) and biomarkers of CNS injury are reported to be increased in plasma but not extensively studied in CSF. This study examines CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19. METHODS: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain protein (NfL) glial fibrillary acidic protein (GFAp) and total tau) was performed and related to neurological features and disease severity. RESULTS: Neurological symptoms included altered mental status (42%), headache (42%), central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL, GFAp and total-tau protein were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL correlated with disease severity, time in intensive care and level of consciousness. NfL in CSF was higher in patients with central neurological symptoms. CONCLUSION: Although limited by small sample size, our data suggest that levels of NfL, GFAp and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF work-up where pathological findings are scarce. NfL in particular, is associated with central neurological symptoms and disease severity

The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care

Background and purpose: A wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood. Material and methods: Patients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology. Results and conclusions: The score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80. Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers

Intracardiac echocardiography to guide transseptal catheterization for radiofrequency catheter ablation of left-sided accessory pathways: two case reports

Intracardiac echocardiography (ICE) is a useful tool for guiding transseptal puncture during electrophysiological mapping and ablation procedures. Left-sided accessory pathways (LSAP) can be ablated by using two different modalities: retrograde approach through the aortic valve and transseptal approach with puncture of the fossa ovalis. We shall report two cases of LSAP where transcatheter radiofrequency ablation (TCRFA) was firstly attempted via transaortic approach with ineffective results. Subsequently, a transseptal approach under ICE guidance has been performed. During atrial septal puncture ICE was able to locate the needle tip position precisely and provided a clear visualization of the "tenting effect" on the fossa ovalis. ICE allowed a better mapping of the mitral ring and a more effective catheter ablation manipulation and tip contact which resulted in a persistent and complete ablation of the accessory pathway with a shorter time of fluoroscopic exposure. ICE-guided transseptal approach might be a promising modality for TCRFA of LSAP

Structure determination of the (1×2) and (1×3) reconstructions of Pt(110) by low-energy electron diffraction

The atomic geometry of the (1×2) and (1×3) structures of the Pt(100) surface has been determined from a low-energy electron-diffraction intensity analysis. Both structures are found to be of the missing-row type, consisting of (111) microfacets, and with similar relaxations in the subsurface layers. In both reconstructions the top-layer spacing is contracted by approximately 20% together with a buckling of about 0.17 Å in the third layer and a small lateral shift of about 0.04 Å in the second layer. Further relaxations down to the fourth layer were detectable. The surface relaxations correspond to a variation of interatomic distances, ranging from -7% to +4%, where in general a contraction of approximately 3% for the distances parallel to the surface occurs. The Pendry and Zanazzi-Jona R factors were used in the analysis, resulting in a minimum value of RP=0.36 and RZJ=0.26 for 12 beams at normal incidence for the (1×2) structure, and similar agreement for 19 beams of the (1×3) structure. The (1×3) structure has been reproducibly obtained after heating the crystal in an oxygen atmosphere of 5×10-6 mbar at 1200 K for about 30 min and could be removed by annealing at 1800 K for 45 min after which the (1×2) structure appeared again. Both reconstructed surfaces are clean within the detection limits of the Auger spectrometer. CO adsorption lifts the reconstruction in both structures. After desorption at 500 K the initial structures appear again, indicating that at least one of the reconstructions does not represent the equilibrium structure of the clean surface and may be stabilized by impurities

Vitamin D, bone turnover markers and hCAP-18 in children with hemato-oncological diseases

Children with hemato-oncological diseases may have significant skeletal morbidities. Vitamin D is essential for the maintenance of skeletal health and may also be important for immunological functions and cancer outcomes. As vitamin D deficiency is a recognized problem in children worldwide, it is important to evaluate its prevalence among children and adolescents with hemato-oncological diseases in Sweden. In this thesis, I investigated vitamin D status and its predictors, serum hCAP-18 (the pro-protein of the antimicrobial peptide LL-37 produced during neutrophil differentiation in the bone marrow), and bone turnover markers in children with hemato-oncological diseases at the time of diagnosis.  Vitamin D deficiency was found in 30.9–46% of the children. Lower 25-hydroxyvitamin D level correlated with older age, seasons outside summer, a more recent calendar year of sampling, lack of vitamin D supplementation, and country of parental origin located between latitudes -45° and 45°. In preschool children with leukemia, a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival.  There was no correlation between serum 25-hydroxyvitamin D and hCAP-18 neither in children with hemato-oncological diseases nor in healthy controls. Children with diseases that impair myelopoiesis presented low hCAP-18 levels, whereas those with non-hematological malignancies displayed serum hCAP-18 levels in the same range as that of healthy children. Children diagnosed with leukemia had lower levels of bone formation and resorption markers than those of children with solid tumors or bone marrow failure. Adolescents with osteosarcoma displayed high bone alkaline phosphatase levels. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid the development of supportive treatments that reduce the adverse effects of cancer and its treatment.

Vitamin D, bone turnover markers and hCAP-18 in children with hemato-oncological diseases

Children with hemato-oncological diseases may have significant skeletal morbidities. Vitamin D is essential for the maintenance of skeletal health and may also be important for immunological functions and cancer outcomes. As vitamin D deficiency is a recognized problem in children worldwide, it is important to evaluate its prevalence among children and adolescents with hemato-oncological diseases in Sweden. In this thesis, I investigated vitamin D status and its predictors, serum hCAP-18 (the pro-protein of the antimicrobial peptide LL-37 produced during neutrophil differentiation in the bone marrow), and bone turnover markers in children with hemato-oncological diseases at the time of diagnosis.  Vitamin D deficiency was found in 30.9–46% of the children. Lower 25-hydroxyvitamin D level correlated with older age, seasons outside summer, a more recent calendar year of sampling, lack of vitamin D supplementation, and country of parental origin located between latitudes -45° and 45°. In preschool children with leukemia, a 25-hydroxyvitamin D level < 50 nmol/L was associated with inferior overall survival.  There was no correlation between serum 25-hydroxyvitamin D and hCAP-18 neither in children with hemato-oncological diseases nor in healthy controls. Children with diseases that impair myelopoiesis presented low hCAP-18 levels, whereas those with non-hematological malignancies displayed serum hCAP-18 levels in the same range as that of healthy children. Children diagnosed with leukemia had lower levels of bone formation and resorption markers than those of children with solid tumors or bone marrow failure. Adolescents with osteosarcoma displayed high bone alkaline phosphatase levels. The identification of patients with suboptimal vitamin D status and compromised bone remodeling at cancer diagnosis may aid the development of supportive treatments that reduce the adverse effects of cancer and its treatment.