Brain damage markers neuron-specific enolase (NSE) and S100B in serum in children with Lyme neuroborreliosis-detection and evaluation as prognostic biomarkers for clinical outcome.

Lyme borreliosis (LB) is the most common tick-borne infection in Europe, with Lyme neuroborreliosis (LNB) its second most frequent clinical manifestation. Prognostic factors for clinical outcomes in LNB have not been identified. Elevated serum levels of the brain damage markers neuron-specific enolase (NSE) and S100 calcium-binding protein B (S100B) have been associated with poor clinical outcomes in other disorders of the central nervous system. The aim of this study is to assess NSE and S100B in serum as prognostic biomarkers for clinical outcomes in paediatric LNB patients. Children evaluated for LNB (n = 121) in Sweden were prospectively included during 2010-2014, serum samples were collected on admission, and all children underwent a 2-month follow-up. Patients with pleocytosis and anti-Borrelia antibodies in cerebrospinal fluid (CSF) were classified as having LNB (n = 61). Controls were age- and gender-matched non-LNB patients (n = 60). NSE was elevated in 38/61 (62%) LNB patients and in 31/60 (52%) controls. S100B was elevated in 3/60 (5%) LNB patients and 0/59 (0%) controls. NSE and S100B concentrations did not differ significantly when comparing LNB patients with controls. No differences were found in the concentrations when comparing the clinical recovery of LNB patients at the 2-month follow-up. NSE was detectable in the majority of LNB patients and controls, whereas S100B was detectable in only a few LNB patients and no controls. NSE and S100B in serum cannot be recommended as prognostic biomarkers for clinical outcomes in children with LNB.

Effectiveness of antibiotic treatment in children with Lyme neuroborreliosis - a retrospective study.

BACKGROUND: Lyme neuroborreliosis (LNB) is a tick-borne infection caused by the spirochete Borrelia burgdorferi sensu lato complex with various neurological manifestations. The recommended treatment for LNB in Swedish children has been intravenous ceftriaxone 50-100 mg/kg × 1 (< 8 years of age) or oral doxycycline 4 mg/kg × 1 (≥ 8 years of age) for 10-14 days. Studies on adult LNB patients have shown equal efficacy for ceftriaxone and doxycycline, but no such studies have been conducted on pediatric LNB patients. The aim of this study is to retrospectively evaluate clinical outcome in children with LNB who have received intravenous ceftriaxone or oral doxycycline. RESULTS: Clinical and laboratory data from three previously conducted prospective studies on children with LNB (1998-2014) were retrospectively analyzed. A total of 321 children (1-19 years of age), who received antibiotic treatment for definite LNB or possible LNB, were included. Clinical outcome at the 2-month follow-up (recovery/non-recovery) was evaluated using Chi2 test and logistic multivariate regression analysis. Out of 321 LNB patients, 194 children (60%) had received ceftriaxone and 127 children (40%) had received doxycycline. When comparing clinical outcome between treatment groups, no difference was found (p = 0,217). Results did not change when incorporating relevant clinical and laboratory data into the logistic multivariate regression analysis. CONCLUSION: In this large retrospective study, no difference in clinical outcome was found, independent of age, when comparing children who received ceftriaxone with those who received doxycycline, supporting an equal effectiveness for treatment of LNB pediatric patients. However, future randomized comparative treatment studies are warranted for evaluation of efficacy of antibiotic treatment in pediatric LNB patients.

The facial nerve palsy and cortisone evaluation (FACE) study in children: protocol for a randomized, placebo-controlled, multicenter trial, in a Borrelia burgdorferi endemic area.

BACKGROUND: Children with acute peripheral facial nerve palsy cannot yet be recommended corticosteroid treatment based on evidence. Adults with idiopathic facial nerve palsy are treated with corticosteroids, according to guidelines resulting from a meta-analysis comprising two major randomized placebo-controlled trials. Corresponding trials in children are lacking. Furthermore, acute facial nerve palsy in childhood is frequently associated with Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi. The efficacy and safety of corticosteroid treatment of acute facial nerve palsy associated with Lyme neuroborreliosis, has not yet been determined in prospective trials in children, nor in adults. METHOD: This randomized double-blind, placebo-controlled study will include a total of 500 Swedish children aged 1-17 years, presenting with acute facial nerve palsy of either idiopathic etiology or associated with Lyme neuroborreliosis. Inclusion is ongoing at 12 pediatric departments, all situated in Borrelia burgdorferi endemic areas. Participants are randomized into active treatment with prednisolone 1 mg/kg/day (maximum 50 mg/day) or placebo for oral intake once daily during 10 days without taper. Cases associated with Lyme neuroborreliosis are treated with antibiotics in addition to the study treatment. The House-Brackmann grading scale and the Sunnybrook facial grading system are used for physician-assessed evaluation of facial impairment at baseline, and at the 1- and 12-month follow-ups. Primary outcome is complete recovery, measured by House-Brackmann grading scale, at the 12-month follow-up. Child/parent-assessed questionnaires are used for evaluation of disease-specific quality of life and facial disability and its correlation to physician-assessed facial impairment will be evaluated. Furthermore, the study will evaluate factors of importance for predicting recovery, as well as the safety profile for short-term prednisolone treatment in children with acute facial nerve palsy. DISCUSSION: This article presents the rationale, design and content of a protocol for a study that will determine the efficacy of corticosteroid treatment in children with acute facial nerve palsy of idiopathic etiology, or associated with Lyme neuroborreliosis. Future results will attribute to evidence-based treatment guidelines applicable also in Borrelia burgdorferi endemic areas. TRIAL REGISTRATION: The study protocol was approved by the Swedish Medical Product Agency (EudraCT nr 2017-004187-35) and published at ClinicalTrials.gov ( NCT03781700 , initial release 12/14/2018).

Peripheral facial nerve palsy in children in a Borrelia high-endemic area, a retrospective follow-up study.

AIM: To identify the incidence, aetiology and prognosis of acute peripheral facial nerve palsy (FNP) in children in the Borrelia high-endemic region of Stockholm. METHODS: The present study identified children from 0 to 18 years of age who visited a paediatric emergency department for acute peripheral FNP during a 1-year period from 2014 to 2015. Data were collected retrospectively. The Sunnybrook and House-Brackmann facial grading systems were used to measure clinical outcome. RESULTS: A total of 77 children were identified with FNP, an estimated incidence of 30 per 100 000 children/year. Forty-five children (58%) were diagnosed with neuroborreliosis, 28 (36%) with idiopathic FNP and four (6%) with other rarer causes. Neuroborreliosis was common from June to November and mainly seen in children below 10 years of age. Six patients (8%) had remaining symptoms at least 3 months after onset; three had idiopathic facial palsy (IFP) and were all older than 10 years, one had neuroborreliosis and two had other causes. CONCLUSION: Neuroborreliosis and IFP were the major causes of FNP during the study period. Neuroborreliosis-associated facial palsy had a seasonal variation and dominated in younger ages.

Bacteraemia in children in Iceland 1994-2005.

AIM: To investigate the aetiology of bacteraemia in children in Iceland, the antibiotic resistance and possible preventive measures. METHODS: All positive bacterial blood cultures from children 0-18 years old isolated at Landspítali University Hospital Iceland from 1994 to 2005 were included in the study. Epidemiological and microbiological data were registered. The blood cultures were categorized according to likelihood of infection or contamination. RESULTS: During the study period 1253 positive blood cultures were obtained from 974 children; 647 from boys and 606 from girls. Positive blood cultures were most common during the first year of life (594; 47.4%) with 252 of them from neonates. Coagulase negative staphylococci were most common (37%). Of probable or definite infections Streptococcus pneumoniae was the most common (19.3%) followed by Staphylococcus aureus (17.6%) and Neisseria meningitidis (13.5%). The most common pneumococcal serogroups were 23, 6, 7, 19 and 14. Commercially available vaccines contain up to 88% of all pneumococcal strains and 67% of all multi-resistant strains. N. meningitidis group C was not isolated after vaccinations were started in 2002. CONCLUSION: Our study provides important epidemiological data on bacterial bloodstream infections in children in Iceland. The results demonstrate the excellent efficacy of meningococcal group C vaccination.

Microplastic ingestion by fish: Body size, condition factor and gut fullness are not related to the amount of plastics consumed.

This study investigates the frequency of microplastic (MP) ingestion and the relationship between microplastics in the guts of two commercial fish species in Iceland (cod; Gadus morhua and saithe; Pollachius virens) and the weight, length, gut fullness, and condition index (CI) of the fish. MPs were found in 20.5% of the cod (n = 39) and 17.4% of the saithe (n = 46). There was no significant correlation between gut fullness nor CI and findings of MPs, indicating that, especially in large individuals, MPs are not retained to a large extent, and if so, the CI is most likely not affected. A difference was found in fish length between fish containing plastic and fish without plastics. Further studies such as this must be conducted in all water ecosystems if we are to fully understand the impact that MP's are having at the individual, population, species, and ecosystem levels.

Breakthrough pain in malignant and non-malignant diseases: a review of prevalence, characteristics and mechanisms.

Breakthrough pain or transient worsening of pain in patients with an ongoing steady pain is a well known feature in cancer pain patients, but it is also seen in non-malignant pain conditions with involvement of nerves, muscles, bones or viscera. Continuous and intermittent pain seems to be a general feature of these different pain conditions, and this raises the possibility of one or several common mechanisms underlying breakthrough pain in malignant and non-malignant disorders. Although the mechanisms of spontaneous ongoing pain and intermittent flares of pain (BTP) may be difficult to separate, we suggest that peripheral and/or central sensitization (hyperexcitability) may play a major role in many causes of BTP. Mechanical stimuli (e.g. micro-fractures) changes in chemical environments and release of tumour growth factors may initiate sensitization both peripherally and centrally. It is suggested that sensitization could be the common denominator of BTP in malignant and non-malignant pain.

Cancer as a complex phenotype: pattern of cancer distribution within and beyond the nuclear family.

BACKGROUND: The contribution of low-penetrant susceptibility variants to cancer is not clear. With the aim of searching for genetic factors that contribute to cancer at one or more sites in the body, we have analyzed familial aggregation of cancer in extended families based on all cancer cases diagnosed in Iceland over almost half a century. METHODS AND FINDINGS: We have estimated risk ratios (RRs) of cancer for first- and up to fifth-degree relatives both within and between all types of cancers diagnosed in Iceland from 1955 to 2002 by linking patient information from the Icelandic Cancer Registry to an extensive genealogical database, containing all living Icelanders and most of their ancestors since the settlement of Iceland. We evaluated the significance of the familial clustering for each relationship separately, all relationships combined (first- to fifth-degree relatives) and for close (first- and second-degree) and distant (third- to fifth-degree) relatives. Most cancer sites demonstrate a significantly increased RR for the same cancer, beyond the nuclear family. Significantly increased familial clustering between different cancer sites is also documented in both close and distant relatives. Some of these associations have been suggested previously but others not. CONCLUSION: We conclude that genetic factors are involved in the etiology of many cancers and that these factors are in some cases shared by different cancer sites. However, a significantly increased RR conferred upon mates of patients with cancer at some sites indicates that shared environment or nonrandom mating for certain risk factors also play a role in the familial clustering of cancer. Our results indicate that cancer is a complex, often non-site-specific disease for which increased risk extends beyond the nuclear family.

Familial risk of lung carcinoma in the Icelandic population.

CONTEXT: The dominant role of tobacco smoke as a causative factor in lung carcinoma is well established; however, an inherited predisposition may also be an important factor in the susceptibility to lung carcinoma. OBJECTIVE: To investigate the contribution of genetic factors to the risk of developing lung carcinoma in the Icelandic population. DESIGN, SETTING, AND PARTICIPANTS: Risk ratios (RRs) of lung carcinoma for first-, second-, and third-degree relatives of patients with lung carcinoma were estimated by linking records from the Icelandic Cancer Registry (ICR) of all 2756 patients diagnosed with lung carcinoma within the Icelandic population from January 1, 1955, to February 28, 2002, with an extensive genealogical database containing all living Icelanders and most of their ancestors since the settlement of Iceland. The RR for smoking was similarly estimated using a random population-based cohort of 10,541 smokers from the Reykjavik Heart Study who had smoked for more than 10 years. Of these smokers, 562 developed lung cancer based on the patients with lung cancer list from the ICR. MAIN OUTCOME MEASURES: Estimation of RRs of close and distant relatives of patients with lung carcinoma and comparison with RRs for close and distant relatives of smokers. RESULTS: A familial factor for lung carcinoma was shown to extend beyond the nuclear family, as evidenced by significantly increased RR for first-degree relatives (for parents: RR, 2.69; 95% confidence interval [CI], 2.20-3.23; for siblings: RR, 2.02; 95% CI, 1.77-2.23; and for children: RR, 1.96; 95% CI, 1.53-2.39), second-degree relatives (for uncles/aunts: RR, 1.34; 95% CI, 1.15-1.49; and for nephews/nieces: RR, 1.28; 95% CI, 1.10-1.43), and third-degree relatives (for cousins: RR, 1.14; 95% CI, 1.05-1.22) of patients with lung carcinoma. This effect was stronger for relatives of patients with early-onset disease (age at onset < or =60 years) (for parents: RR, 3.48; 95% CI, 1.83-8.21; for siblings: RR, 3.30; 95% CI, 2.19-4.58; and for children: RR, 2.84; 95% CI, 1.34-7.21). The hypothesis that this increased risk is solely due to the effects of smoking was rejected for all relationships, except cousins and spouses, with a single-sided test of the RRs for lung carcinoma vs RRs for smoking. CONCLUSIONS: These results underscore the importance of genetic predisposition in the development of lung carcinoma, with its strongest effect in patients with early-onset disease. However, tobacco smoke plays a dominant role in the pathogenesis of this disease, even among those individuals who are genetically predisposed to lung carcinoma.

[Bacteraemia in children in Iceland 1994-2005]. / Blódsýkingar barna á Islandi 1994-2005.

OBJECTIVE: Positive blood cultures from children suggest serious bloodstream infections. Quick medical response with targeted therapy is important, taking the child's age and medical history into account. Antibiotic therapy and vaccination programs must be based on accurate knowledge of the prevalence and antibiotic susceptibility of the bacteria. The aim of this study was to investigate epidemiological parameters associated with positive blood cultures in children in Iceland from September 20th 1994 to March 16th 2005. MATERIALS AND METHODS: All positive bacterial blood cultures from children 0-18 years of age identified at the Department of Clinical Microbiology of the Landspitali University Hospital during the study period. Age and sex of the children, bacterial aetiology, date of collection and results of antimicrobial susceptibility tests were registered. The children were divided into four age groups: neonates (< or =30 days of age), infants (30 days to one year), preschool age (1-6 y) and school age (6-18 y). The blood cultures were classified as definite contamination, probable contamination, probable infection and definite infection. RESULTS: During the study period 1253 positive blood cultures were obtained from 974 children; 647 from boys and 606 from girls. Most of the blood cultures were from children less than one year old (594; 47.4%) of which 252 were neonates (42.4% of all children <1 y of age). Coagulase negative staphylococci were the most commonly isolated organisms (37%). Of positive blood cultures considered definite infections Streptococcus pneumoniae was the most common (21.7%) followed by Staphylococcus aureus (19.8%) and Neisseria meningitidis (15.2%). N. meningitidis C was not isolated in children after a meningococcal C vaccination was launched in 2002. The most common pneumococcal serotypes/serogroups were 23, 6B, 7, 19 and 14. Macrolide resistance was common in pneumococci (19%) and group A haemolytic streptococci (33%). CONCLUSION: The results provide important information for empirical antibiotical therapy and prophylactic measures such as vaccination. Increasing macrolide resistance limits their usefulness as empiric antibiotics in septic children. The results demonstrate the excellent efficacy of meningococcal C vaccination. Furthermore the results help in predicting the efficacy of pneumococcal vaccination of Icelandic children.