Preadmission course and management of severe pediatric group A streptococcal infections during the 2022-2023 outbreak: a single-center experience.

PURPOSE: The massive increase of infections with Group A Streptococcus (GAS) in 2022-2023 coincided in Switzerland with a change of the recommendations for the management of GAS pharyngitis. Therefore, the objective of the present study was to investigate whether the clinical manifestations and management before hospitalization for GAS infection differed in 2022-2023 compared with 2013-2022. METHODS: Retrospective study of GAS infections requiring hospitalization in patients below 16 years. Preadmission illness (modified McIsaac score), oral antibiotic use, and outcome in 2022-2023 were compared with 2013-2022. Time series were compared with surveillance data for respiratory viruses. RESULTS: In 2022-2023, the median modified McIsaac score was lower (2 [IQR 2-3] vs. 3 [IQR 2-4], p = < 0.0001) and the duration of preadmission illness was longer (4 days [3-7] vs. 3 [2-6], p = 0.004) than in 2013-2022. In both periods, withholding of preadmission oral antibiotics despite a modified McIsaac score ≥ 3 (12% vs. 18%, n.s.) or ≥ 4 (2.4% vs. 10.0%, p = 0.027) was rare. Respiratory disease, skeletal/muscle infection, and invasive GAS disease were significantly more frequent in 2022-2023, but there were no differences in clinical outcome. The time course of GAS cases in 2022-2023 coincided with the activity of influenza A/B. CONCLUSION: We found no evidence supporting the hypothesis that the 2022-2023 GAS outbreak was associated with a change in preadmission management possibly induced by the new recommendation for GAS pharyngitis. However, clinical manifestations before admission and comparative examination of time-series strongly suggest that viral co-circulation played an important role in this outbreak.

Organ Dysfunction in Children With Blood Culture-Proven Sepsis: Comparative Performance of Four Scores in a National Cohort Study.

OBJECTIVES: Previous studies applying Sepsis-3 criteria to children were based on retrospective analyses of PICU cohorts. We aimed to compare organ dysfunction criteria in children with blood culture-proven sepsis, including emergency department, PICU, and ward patients, and to assess relevance of organ dysfunctions for mortality prediction. DESIGN: We have carried out a nonprespecified, secondary analysis of a prospective dataset collected from September 2011 to December 2015. SETTING: Emergency departments, wards, and PICUs in 10 tertiary children's hospitals in Switzerland. PATIENTS: Children younger than 17 years old with blood culture-proven sepsis. We excluded preterm infants and term infants younger than 7 days old. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We compared the 2005 International Pediatric Sepsis Consensus Conference (IPSCC), Pediatric Logistic Organ Dysfunction-2 (PELOD-2), pediatric Sequential Organ Failure Assessment (pSOFA), and Pediatric Organ Dysfunction Information Update Mandate (PODIUM) scores, measured at blood culture sampling, to predict 30-day mortality. We analyzed 877 sepsis episodes in 807 children, with a 30-day mortality of 4.3%. Percentage with organ dysfunction ranged from 32.7% (IPSCC) to 55.3% (pSOFA). In adjusted analyses, the accuracy for identification of 30-day mortality was area under the curve (AUC) 0.87 (95% CI, 0.82-0.92) for IPSCC, 0.83 (0.76-0.89) for PELOD-2, 0.85 (0.78-0.92) for pSOFA, and 0.85 (0.78-0.91) for PODIUM. When restricting scores to neurologic, respiratory, and cardiovascular dysfunction, the adjusted AUC was 0.89 (0.84-0.94) for IPSCC, 0.85 (0.79-0.91) for PELOD-2, 0.87 (0.81-0.93) for pSOFA, and 0.88 (0.83-0.93) for PODIUM. CONCLUSIONS: IPSCC, PELOD-2, pSOFA, and PODIUM performed similarly to predict 30-day mortality. Simplified scores restricted to neurologic, respiratory, and cardiovascular dysfunction yielded comparable performance.

SARS-CoV-2 Infection During Induction Chemotherapy in a Child With High-risk T-Cell Acute Lymphoblastic Leukemia.

The clinical course of SARS-CoV-2 infection (COVID-19) in children with hematologic malignancies is unclear. We describe the diagnosis, treatment and outcome of a 4-year-old boy with high-risk acute lymphoblastic leukemia and COVID-19. Regardless of immunosuppressive induction chemotherapy his symptoms remained moderate. He received only supportive treatment. Seroconversion occurred in a similar period as in immunocompetent adults. Despite prolonged myelosuppression he did neither acquire secondary infections nor did the treatment delay caused by the infection have a measurable negative impact on the residual disease of acute lymphoblastic leukemia. Intriguingly, residual leukemia even decreased even though he did not receive any antileukemic therapy.

Whole-exome Sequencing for the Identification of Rare Variants in Primary Immunodeficiency Genes in Children With Sepsis: A Prospective, Population-based Cohort Study.

BACKGROUND: The role of primary immunodeficiencies (PID) in susceptibility to sepsis remains unknown. It is unclear whether children with sepsis benefit from genetic investigations. We hypothesized that sepsis may represent the first manifestation of underlying PID. We applied whole-exome sequencing (WES) to a national cohort of children with sepsis to identify rare, predicted pathogenic variants in PID genes. METHODS: We conducted a multicenter, population-based, prospective study including previously healthy children aged ≥28 days and <17 years admitted with blood culture-proven sepsis. Using a stringent variant filtering procedure, analysis of WES data was restricted to rare, predicted pathogenic variants in 240 PID genes for which increased susceptibility to bacterial infection has been reported. RESULTS: There were 176 children presenting with 185 sepsis episodes who underwent WES (median age, 52 months; interquartile range, 15.4-126.4). There were 41 unique predicted pathogenic PID variants (1 homozygous, 5 hemizygous, and 35 heterozygous) found in 35/176 (20%) patients, including 3/176 (2%) patients carrying variants that were previously reported to lead to PID. The variants occurred in PID genes across all 8 PID categories, as defined by the International Union of Immunological Societies. We did not observe a significant correlation between clinical or laboratory characteristics of patients and the presence or absence of PID variants. CONCLUSIONS: Applying WES to a population-based cohort of previously healthy children with bacterial sepsis detected variants of uncertain significance in PID genes in 1 out of 5 children. Future studies need to investigate the functional relevance of these variants to determine whether variants in PID genes contribute to pediatric sepsis susceptibility.

Burden of Streptococcus pneumoniae Sepsis in Children After Introduction of Pneumococcal Conjugate Vaccines: A Prospective Population-based Cohort Study.

BACKGROUND: Population-based studies assessing the impact of pneumococcal conjugate vaccines (PCV) on burden of pneumococcal sepsis in children are lacking. We aimed to assess this burden following introduction of PCV-13 in a nationwide cohort study. METHODS: The Swiss Pediatric Sepsis Study (September 2011 to December 2015) prospectively recruited children <17 years of age with blood culture-proven sepsis due to Streptococcus pneumoniae, meeting criteria for systemic inflammatory response syndrome. Infection with vaccine serotype in children up to date with PCV immunization was defined as vaccine failure. Main outcomes were admission to pediatric intensive care unit (PICU) and length of hospital stay (LOS). RESULTS: Children with pneumococcal sepsis (n = 117) accounted for a crude incidence of 2.0 per 100 000 children (95% confidence interval [CI] 1.7-2.4) and 25% of community-acquired sepsis episodes. Case fatality rate was 8%. Forty-two (36%) patients required PICU admission. Children with meningitis (29; 25%) were more often infected by serotypes not included in PCV (69% vs 31%; P < .001). Sixteen (26%) of 62 children up to date with PCV immunization presented with vaccine failure, including 11 infected with serotype 3. In multivariable analyses, children with meningitis (odds ratio [OR] 6.8; 95% CI 2.4-19.3; P < .001) or infected with serotype 3 (OR 2.8; 95% CI 1.1-7.3; P = .04) were more often admitted to PICU. Children infected with serotype 3 had longer LOS (ß coefficient 0.2, 95% CI .1-1.1; P = .01). CONCLUSIONS: The incidence of pneumococcal sepsis in children shortly after introduction of PCV-13 remained substantial. Meningitis mostly due to non-vaccine serotypes and disease caused by serotype 3 represented significant predictors of severity.

Neonatal Sepsis of Early Onset, and Hospital-Acquired and Community-Acquired Late Onset: A Prospective Population-Based Cohort Study.

OBJECTIVE: To assess the epidemiology of blood culture-proven early- (EOS) and late-onset neonatal sepsis (LOS). STUDY DESIGN: All newborn infants admitted to tertiary care neonatal intensive care units in Switzerland and presenting with blood culture-proven sepsis between September 2011 and December 2015 were included in the study. We defined EOS as infection occurring <3 days after birth, and LOS as infection ≥3 days after birth. Infants with LOS were classified as having community-acquired LOS if onset of infection was ≤48 hours after admission, and hospital-acquired LOS, if onset was >48 hours after admission. Incidence was estimated based on the number of livebirths in Switzerland and adjusted for the proportion of admissions at centers participating in the study. RESULTS: We identified 444 episodes of blood culture-proven sepsis in 429 infants; 20% of cases were EOS, 62% hospital-acquired LOS, and 18% community-acquired LOS. The estimated national incidence of EOS, hospital-acquired LOS, and community-acquired LOS was 0.28 (95% CI 0.23-0.35), 0.86 (0.76-0.97), and 0.28 (0.23-0.34) per 1000 livebirths. Compared with EOS, hospital-acquired LOS occurred in infants of lower gestational age and was more frequently associated with comorbidities. Community-acquired LOS was more common in term infants and in male infants. Mortality was 18%, 12%, and 0% in EOS, hospital-acquired LOS, and community-acquired LOS, and was higher in preterm infants, in infants with septic shock, and in those requiring mechanical ventilation. CONCLUSIONS: We report a high burden of sepsis in neonates with considerable mortality and morbidity. EOS, hospital-acquired LOS, and community-acquired LOS affect specific patient subgroups and have distinct clinical presentation, pathogens and outcomes.

Patterns of paediatric end-of-life care: a chart review across different care settings in Switzerland.

BACKGROUND: Paediatric end-of-life care is challenging and requires a high level of professional expertise. It is important that healthcare teams have a thorough understanding of paediatric subspecialties and related knowledge of disease-specific aspects of paediatric end-of-life care. The aim of this study was to comprehensively describe, explore and compare current practices in paediatric end-of-life care in four distinct diagnostic groups across healthcare settings including all relevant levels of healthcare providers in Switzerland. METHODS: In this nationwide retrospective chart review study, data from paediatric patients who died in the years 2011 or 2012 due to a cardiac, neurological or oncological condition, or during the neonatal period were collected in 13 hospitals, two long-term institutions and 10 community-based healthcare service providers throughout Switzerland. RESULTS: Ninety-three (62%) of the 149 reviewed patients died in intensive care units, 78 (84%) of them following withdrawal of life-sustaining treatment. Reliance on invasive medical interventions was prevalent, and the use of medication was high, with a median count of 12 different drugs during the last week of life. Patients experienced an average number of 6.42 symptoms. The prevalence of various types of symptoms differed significantly among the four diagnostic groups. Overall, our study patients stayed in the hospital for a median of six days during their last four weeks of life. Seventy-two patients (48%) stayed at home for at least one day and only half of those received community-based healthcare. CONCLUSIONS: The study provides a wide-ranging overview of current end-of-life care practices in a real-life setting of different healthcare providers. The inclusion of patients with all major diagnoses leading to disease- and prematurity-related childhood deaths, as well as comparisons across the diagnostic groups, provides additional insight and understanding for healthcare professionals. The provision of specialised palliative and end-of-life care services in Switzerland, including the capacity of community healthcare services, need to be expanded to meet the specific needs of seriously ill children and their families.

Moraxella catarrhalis AcrAB-OprM efflux pump contributes to antimicrobial resistance and is enhanced during cold shock response.

Moraxella catarrhalis is a common pathogen of the human respiratory tract. Multidrug efflux pumps play a major role in antibiotic resistance and virulence in many Gram-negative organisms. In the present study, the role of the AcrAB-OprM efflux pump in antibiotic resistance was investigated by constructing mutants that lack the acrA, acrB, and oprM genes in M. catarrhalis strain O35E. We observed a moderate (1.5-fold) decrease in the MICs of amoxicillin and cefotaxime and a marked (4.7-fold) decrease in the MICs of clarithromycin for acrA, acrB, and oprM mutants in comparison with the wild-type O35E strain. Exposure of the M. catarrhalis strains O35E and 300 to amoxicillin triggered an increased transcription of all AcrAB-OprM pump genes, and exposure of strains O35E, 300, and 415 to clarithromycin enhanced the expression of acrA and oprM mRNA. Inactivation of the AcrAB-OprM efflux pump genes demonstrated a decreased ability to invade epithelial cells compared to the parental strain, suggesting that acrA, acrB, and oprM are required for efficient invasion of human pharyngeal epithelial cells. Cold shock increases the expression of AcrAB-OprM efflux pump genes in all three M. catarrhalis strains tested. Increased expression of AcrAB-OprM pump genes after cold shock leads to a lower accumulation of Hoechst 33342 (H33342), a substrate of AcrAB-OprM efflux pumps, indicating that cold shock results in increased efflux activity. In conclusion, the AcrAB-OprM efflux pump appears to play a role in the antibiotic resistance and virulence of M. catarrhalis and is involved in the cold shock response.

Synthetic versus natural curcumin: bioequivalence in an in vitro oral mucositis model.

BACKGROUND: Curcumin (CUR) is a dietary spice and food colorant (E100). Its potent anti-inflammatory activity by inhibiting the activation of Nuclear Factor-κB is well established. METHODS: The aim of this study was to compare natural purified CUR (nCUR) with synthetically manufactured CUR (sCUR) with respect to their capacity to inhibit detrimental effects in an in vitro model of oral mucositis. The hypothesis was to demonstrate bioequivalence of nCUR and sCUR. RESULTS: The purity of sCUR was HPLC-confirmed. Adherence and invasion assays for bacteria to human pharyngeal epithelial cells demonstrated equivalence of nCUR and sCUR. Standard assays also demonstrated an identical inhibitory effect on pro-inflammatory cytokine/chemokine secretion (e.g., interleukin-8, interleukin-6) by Detroit pharyngeal cells exposed to bacterial stimuli. There was bioequivalence of sCUR and nCUR with respect to their antibacterial effects against various pharyngeal species. CONCLUSION: nCUR and sCUR are equipotent in in vitro assays mimicking aspects of oral mucositis. The advantages of sCUR include that it is odorless and tasteless, more easily soluble in DMSO, and that it is a single, highly purified molecule, lacking the batch-to-batch variation of CUR content in nCUR. sCUR is a promising agent for the development of an oral anti-mucositis agent.

Epidemiology and Clinical Characteristics of Human Metapneumovirus Infections in Hospitalized Children in Two Consecutive Postpandemic Years.

We assessed human metapneumovirus infections in children hospitalized between 2011 and 2023 and compared the strongest pre- and postpandemic seasons. After the COVID-19 pandemic, we observed offseason cases and loss of the alternating pattern of the human metapneumovirus season magnitude. Incidence rate ratio of 0- to 11-month-old versus 12- to 23-month-old children was 2.1 (95% CI: 1.0-4.8) before and 1.3 (95% CI: 0.6-2.9) after the pandemic.

Seroepidemiology of Human Tularemia-Systematic Review and Meta-analysis of Seroprevalence Studies.

Background: Seroepidemiologic studies of human tularemia have been conducted throughout the northern hemisphere. The purposes of this study were (1) to provide an overview of Francisella tularensis seroprevalence data, and (2) to generate an estimate of the proportion of study participants whose infection remained subclinical. Methods: We conducted a systematic review of F tularensis seroprevalence studies according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched PubMed, Embase, and Web of Science covering the period from 1951 to 2023. Results: The weighted pooled seroprevalence among 44 486 participants recruited in 52 studies was 3.7% (95% confidence interval [CI], 2.7-5.1). Reported seroprevalences ranged between 0.2% and 31.3%. Occupational activities associated with an increased likelihood of exposure (risk ratio, 3.51 [95% CI, 3.2-3.86]) and studies from North America versus Europe and Asia (4.53 [4.15-4.94]) were associated with significantly increased seropositive rates. Twenty-eight data sets (47%) reported clinical information on a total of 965 seropositive participants. The weighted pooled estimate for subclinical seropositivity was 84.4% (95% CI, 72.9%-991.7%). Studies from F tularensis type A areas (risk ratio, 0.37 [95% CI, .27-.51) and studies from sites where pulmonary tularemia prevailed (0.38 [.28-.51]) reported lower subclinical seropositivity rates than studies from type B areas and from areas of predominance of (ulcero)glandular or oropharyngeal tularemia, respectively. Conclusions: Throughout the northern hemisphere, only a small proportion of study participants showed serologic evidence of exposure to F tularensis. Eight of 10 seropositive participants had no historical evidence of past clinical tularemia.

Impact of the availability of an influenza virus rapid antigen test on diagnostic decision making in a pediatric emergency department.

OBJECTIVES: Fever is one of the most commonly seen symptoms in the pediatric emergency department. The objective of this study was to observe how the rapid testing for influenza virus impacts on the management of children with fever. METHODS: We performed a review of our pediatric emergency department records during the 2008/2009 annual influenza season. The BinaxNow Influenza A+B test was performed on patients with the following criteria: age 1.0 to 16.0 years, fever greater than 38.5 °C, fever of less than 96 hours' duration after the onset of clinical illness, clinical signs compatible with acute influenza, and nontoxic appearance. Additional laboratory tests were performed at the treating physician's discretion. RESULTS: The influenza rapid antigen test was performed in 192 children. One hundred nine (57%) were influenza positive, with the largest fraction (101 patients) positive for influenza A. The age distribution did not differ between children with negative and positive test results (mean, 5.3 vs. 5.1 years, not statistically significant). A larger number of diagnostic tests were performed in the group of influenza-negative patients. Twice as many complete blood counts, C-reactive protein determinations, lumbar punctures, and urinalyses were ordered in the latter group. CONCLUSIONS: Rapid diagnosis of influenza in the pediatric emergency department affects the management of febrile children as the confirmation of influenza virus infection decreases additional diagnostic tests ordered.

Acute flaccid myelitis in Switzerland - association with enterovirus D68.

Poliomyelitis-like acute flaccid myelitis associated with enterovirus D68 (EV-D68) has emerged globally during the past decade. Here we describe the first documented case reported from Switzerland, and a second, suspected case occurring in temporal association. AFM occurs primarily in children, is usually heralded by a febrile, respiratory prodrome followed by acute-onset, usually asymmetrical, limb weakness with some predilection for the upper extremities, and respiratory muscle compromise in one third of reported cases. There is no specific therapy and the majority of cases result in permanent neurological sequelae. A comprehensive diagnostic workup and timely reporting to the health authorities are essential. Surveillance of respiratory and stool samples for EV-D68 and other neurotropic enteroviruses is in place in several European countries and warrants consideration in Switzerland. This could entail the extension of the poliomyelitis surveillance program of the Federal Office of Public Health by monitoring and enteroviral typing of respiratory samples from patients with acute flaccid paralysis.

www.coronabambini.ch: Development and usage of an online decision support tool for paediatric COVID-19-testing in Switzerland: a cross-sectional analysis.

OBJECTIVES: To describe the development and usage of www.coronabambini.ch as an example of a paediatric electronic public health application and to explore its potential and limitations in providing information on disease epidemiology and public health policy implementation. DESIGN: We developed and maintained a non-commercial online decision support tool, www.coronabambini.ch, to translate the Swiss Federal Office of Public Health (FOPH) paediatric (age 0-18 years) COVID-19 guidelines around testing and school/daycare attendance for caregivers, teachers and healthcare personnel. We analysed the online decision tool as well as a voluntary follow-up survey from October 2020 to September 2021 to explore its potential as a surveillance tool for public health policy and epidemiology. PARTICIPANTS: 68 269 users accessed and 52 726 filled out the complete online decision tool. 3% (1399/52 726) filled out a voluntary follow-up. 92% (18 797/20 330) of users were parents. RESULTS: Certain dynamics of the pandemic and changes in testing strategies were reflected in the data captured by www.coronabambini.ch, for example, in terms of disease epidemiology, gastrointestinal symptoms were reported more frequently in younger age groups (13% (3308/26 180) in children 0-5 years vs 9% (3934/42 089) in children ≥6 years, χ2=184, p≤0.001). As a reflection of public health policy, the proportion of users consulting the tool for a positive contact without symptoms in children 6-12 years increased from 4% (1415/32 215) to 6% (636/9872) after the FOPH loosened testing criteria in this age group, χ2=69, p≤0.001. Adherence to the recommendation was generally high (84% (1131/1352)) but differed by the type of recommendation: 89% (344/385) for 'stay at home and observe', 75% (232/310) for 'school attendance'. CONCLUSIONS: Usage of www.coronabambini.ch was generally high in areas where it was developed and promoted. Certain patterns in epidemiology and adherence to public health policy could be depicted but selection bias was difficult to measure showing the potential and challenges of digital decision support as public health tools.

Childhood vaccination coverage and regional differences in Swiss birth cohorts 2012-2021: Are we on track?

AIMS: Many western countries are challenged by delayed and insufficient vaccination coverage rates in children, and thus missing WHO coverage targets. This study aimed to estimate vaccination coverage and timeliness in Swiss children over a decade. Furthermore, we evaluated the impact of COVID-19, regional variations, and the adherence to the amended vaccination schedule in 2019. METHODS: Retrospective observational study with Swiss health insurance claims data including birth cohorts 2012-2021 of children continuously observed until ages 13, 25, and 48 months respectively. We used population-weighted proportions and time-to-event analyses to describe coverage and timeliness of diphtheria/tetanus/pertussis/poliomyelitis/haemophilus influenzae type b (DTaP-IPV-Hib), measles/mumps/rubella (MMR), hepatitis B (HBV), pneumococcal (PCV), and meningococcal (MCV) vaccinations according to the national schedule. The potential impact of COVID-19 and vaccination schedule adherence were evaluated descriptively. Logistic regression was used to investigate regional factors potentially associated with non-vaccination. RESULTS: 120,073 children, representing between 12 and 17 % of all Swiss children born in corresponding years, were included. Coverage remained stable or improved over the years. The 2019 amendment of the national immunization schedule was associated with an increase of ~10 % points in full coverage in Swiss children for DTaP-IPV-Hib, MMR and HBV despite the concurrent COVID-19 pandemic. Nonetheless, full vaccination coverage remained below 90 % with many vaccination series being delayed or not completed. The comparison across the different vaccines revealed large differences in coverage. Moreover, we observed large regional differences in non-vaccination with children living in rural and German-speaking areas more likely to be entirely unvaccinated. CONCLUSION: Full vaccination coverage in Swiss children is still below 90 % with many vaccinations administered delayed. Given regional differences, missed or delayed booster vaccinations, and differences in vaccine-specific acceptability, more effort may be needed to achieve national vaccination targets.

Sensitivity of ICD coding for sepsis in children-a population-based study.

Background: International Classification of Diseases 10th edition (ICD-10) is widely used to describe the burden of disease. Aim: To describe how well ICD-10 coding captures sepsis in children admitted to the hospital with blood culture-proven bacterial or fungal infection and systemic inflammatory response syndrome. Methods: Secondary analysis of a population-based, multicenter, prospective cohort study on children with blood culture-proven sepsis of nine tertiary pediatric hospitals in Switzerland. We compared the agreement of validated study data on sepsis criteria with ICD-10 coding abstraction obtained at the participating hospitals. Results: We analyzed 998 hospital admissions of children with blood culture-proven sepsis. The sensitivity of ICD-10 coding abstraction was 60% (95%-CI 57-63) for sepsis; 35% (95%-CI 31-39) for sepsis with organ dysfunction, using an explicit abstraction strategy; and 65% (95%-CI 61-69) using an implicit abstraction strategy. For septic shock, the sensitivity of ICD-10 coding abstraction was 43% (95%-CI 37-50). Agreement of ICD-10 coding abstraction with validated study data varied by the underlying infection type and disease severity (p < 0.05). The estimated national incidence of sepsis, inferred from ICD-10 coding abstraction, was 12.5 per 100,000 children (95%-CI 11.7-13.5) and 21.0 per 100,000 children (95%-CI 19.8-22.2) using validated study data. Conclusions: In this population-based study, we found a poor representation of sepsis and sepsis with organ dysfunction by ICD-10 coding abstraction in children with blood culture-proven sepsis when compared against a prospective validated research dataset. Sepsis estimates in children based on ICD-10 coding may thus severely underestimate the true prevalence of the disease. Supplementary Information: The online version contains supplementary material available at 10.1007/s44253-023-00006-1.

Antibacterial and antiinflammatory kinetics of curcumin as a potential antimucositis agent in cancer patients.

The antiinflammatory agent curcumin (diferuloylmethane) has a potential to mitigate cancer therapy-induced mucositis. We assessed the in vitro extent of its bactericidal activity and determined the kinetics of its antiinflammatory effect on pharyngeal cells. Bactericidal activity was assessed using the LIVE/DEAD® Kit after 4 h of exposure to curcumin (50-200 µM) in 18 oropharyngeal species commonly associated with bacteremia in febrile neutropenia. Moraxella catarrhalis or its outer membrane vesicles were used to determine the inhibitory effect of curcumin on bacteria-induced proinflammatory activity as determined by cytokine release into the supernatant of Detroit 562 pharyngeal cells using the Luminex® xMAP® technology. Curcumin exerted a concentration-dependent bactericidal effect on all 18 species tested. After 4 h at 200 µM, 12 species tested were completely killed. Preincubation of Detroit cells with 200 µM curcumin for 5 to 60 min resulted in complete suppression of the release of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein 1, granulocyte macrophage-colony stimulating factor, and vascular endothelial growth factor. Fibroblast growth factor-2 and interferon-γ were not affected. Repetitive exposure to curcumin resulted in repetitive suppression of cytokine/chemokine expression lasting from 4 to 6 h. Through reduction of oral microbial density as well as suppression of inflammation cascades curcumin may prevent cancer therapy-induced oral mucositis, e.g., when applied as multiple daily mouth washes.

M-ficolin concentrations in cord blood are related to circulating phagocytes and to early-onset sepsis.

INTRODUCTION: The pattern-recognition molecule M-ficolin is synthesized by monocytes and neutrophils. M-ficolin activates the complement system in a manner similar to mannan-binding lectin (MBL), but little is known about its role in host defense. Neonates are highly vulnerable to bacterial sepsis, in particular, due to their decreased phagocytic function. RESULTS: M-ficolin cord blood concentration was positively correlated with the absolute phagocyte count (ρ 0.51, P < 0.001) and with immature/total neutrophil ratio (ρ 0.34, P < 0.001). When comparing infants with sepsis and controls, a high M-ficolin cord blood concentration (>1,000 ng/ml) was associated with early-onset sepsis (EOS) (multivariate odds ratio 10.92, 95% confidence interval 2.21-54.02, P = 0.003). Experimental exposure of phagocytes isolated from adult donors to Escherichia coli resulted in a significant time- and dose-dependent release of M-ficolin. DISCUSSION: In conclusion, M-ficolin concentrations were related to circulating phagocytes and EOS. Our results indicate that bacterial sepsis can trigger M-ficolin release by phagocytes. Future studies should investigate whether M-ficolin may be used as a marker of neutrophil activation during invasive infections. METHODS: We investigated M-ficolin in 47 infants with culture-positive sepsis during the first 30 days of life (13 with EOS and in 94 matched controls. M-ficolin was measured in cord blood using time-resolved immunofluorometric assay (TRIFMA). Multivariate logistic regression was performed.

Serious medical complications in children with cancer and fever in chemotherapy-induced neutropenia: results of the prospective multicenter SPOG 2003 FN study.

BACKGROUND: Fever and chemotherapy-induced neutropenia (FN) is the most frequent potentially lethal complication of therapy in children with cancer. This study aimed to describe serious medical complications (SMC) in children with FN regarding incidence, clinical spectrum, and associated characteristics. PROCEDURE: Pediatric patients presenting with FN induced by non-myeloablative chemotherapy were observed in a prospective multicenter study. SMC was defined as potentially life-threatening complication (PLTC), transfer to the pediatric intensive care unit (PICU), or death. RESULTS: A total of 443 FN episodes were reported from 8 centers. Of these, 411 episodes were reported from 4 centers recruiting consecutively and without bias regarding the risk of complications. They were used for calculation of proportions. An SMC was reported in 23 episodes [5.6%; 95% confidence interval (CI): 3.7-8.1], usually defined by more than one criterion. These were PLTC in 13 episodes, PICU in 22, and death in 3 (mortality, 0.7%; 95% CI: 0.2-2.1). Both a delayed onset of SMC (14 of 23 episodes, 61%) and a biphasic clinical course (11 of 23, 48%) were frequently observed. In a multivariate logistic regression analysis, 4 characteristics were significantly and independently associated with the risk of SMC: diagnosis of acute myeloid leukemia, interval since chemotherapy ≤7 days, severely reduced general condition, and hemoglobin ≥9.0 g/dl at presentation. CONCLUSIONS: In children with FN, SMC were rare, and mortality was very low. Those with SMC often had a delayed onset and biphasic clinical course with secondary deterioration.