The effect of taurolidine on the time-to-positivity of blood cultures.

Background: Taurolidine containing lock solutions (TL) are a promising method for the prevention of central line associated bloodstream infections. Per accident, the TL may not always be aspirated from the central venous catheter (CVC) before blood cultures are obtained. The TL could, unintentionally, end up in a blood culture vial, possibly altering the results. The aim of this study was to investigate the effect of the TLs on the detection of microbial growth in blood culture vials. Methods: Different lock solutions (taurolidine-citrate-heparin (TCHL), taurolidine, heparin, citrate or NaCl) were added to BD BACTECTM blood culture vials (Plus Aerobic/F, Lytic/10 Anaerobic/F or Peds Plus/F) before spiking with Staphylococcus aureus (ATCC 29213 or a clinical strain) or Escherichia coli (ATCC 25922 or a clinical strain) in the presence and absence of blood. Subsequently, blood culture vials were incubated in the BD BACTEC FX instrument with Time-to-positivity (TTP) as primary outcome. In addition, the effect of the TCHL on a variety of other micro-organisms was tested. Discussion: In the presence of taurolidine, the TTP was considerably delayed or vials even remained negative as compared to vials containing heparin, citrate or NaCl. This effect was dose-dependent. The delayed TTP was much less pronounced in the presence of blood, but still notable. Conclusion: This study stresses the clinical importance of discarding TLs from the CVC before obtaining a blood culture.

Satisfaction of Paediatric Oncology Patients, Survivors, and Nurses with the Position of Their Totally Implantable Venous Access Port (SPACE-Study).

BACKGROUND: To compare paediatric oncologic vascular access ports located on the anterior thoracic wall to ports on the lower lateral thoracic wall, in terms of perceived port-related hindrance and scar-quality. METHODS: A cross-sectional survey study including paediatric oncology patients (≥8-<19 yrs), caregivers (in patients <8 yrs), survivors (>22 yrs with only anterior ports) and nurses of the Princess Máxima Center, the Netherlands, was performed. The survey consisted of questions regarding satisfaction, hindrance during daily life, and port position preference. For survivors, scar-quality was assessed using the validated Patient and Observer Scar Assessment Scale (POSAS 2.0); a high score (i.e., a displeasing scar) was defined as a score higher than the third quartile of the median for that question. RESULTS: In total, 147 participants were included; 83 patients/caregivers, 31 survivors, and 33 nurses. Overall, 81 % was satisfied with the position of their port. Satisfaction, hindrance and complications did not differ between anterior and lower lateral ports. For the anterior position, minimal pressure on the port during daily life was a mentioned reason to prefer this position. For the lower lateral position, less visibility of the scar and easiest access were mentioned. Of all survivors with an anterior port scar, one in five had a displeasing scar and all scars observed were widened. Female patients preferred a lower lateral port, and scar-quality was better for left-sided port scars. CONCLUSION: The port position should be chosen together with patients/caregivers based on the (dis-)advantages of each position, as identified by this study. LEVEL OF EVIDENCE: II.

The efficacy of taurolidine containing lock solutions for the prevention of central-venous-catheter-related bloodstream infections: a systematic review and meta-analysis.

The incidence of central venous catheter (CVC)-related bloodstream infections is high in patients requiring a long-term CVC. Therefore, infection prevention is of the utmost importance. The aim of this study was to provide an updated overview of randomized controlled trials (RCTs) comparing the efficacy of taurolidine containing lock solutions (TL) to other lock solutions for the prevention of CVC-related bloodstream infections in all patient populations. On 15th February 2021, PubMed, Embase and The Cochrane Library were searched for RCTs comparing the efficacy of TLs for the prevention of CVC-related bloodstream infections with other lock solutions. Exclusion criteria were non-RCTs, studies describing <10 patients and studies using TLs as treatment. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A random effects model was used to pool individual study incidence rate ratios (IRRs). Subgroup analyses were performed based on the following factors: CVC indication, comparator lock and bacterial isolates cultured. A total of 14 articles were included in the qualitative synthesis describing 1219 haemodialysis, total parenteral nutrition and oncology patients. The pooled IRR estimated for all patient groups together (nine studies; 918 patients) was 0.30 (95% confidence interval 0.19-0.46), favouring the TLs. Adverse events (10 studies; 867 patients) were mild and scarce. The quality of the evidence was limited due to a high risk of bias and indirectness of evidence. The use of TLs might be promising for the prevention of CVC-related bloodstream infections. Large-scale RCTs are needed to draw firm conclusions on the efficacy of TLs.

Chemotherapy intravenously in children with cancer at home, the nurse practitioner makes it possible!

BACKGROUND: Currently the entire treatment of a child with cancer is carried out in a specialized hospital. It would be ideal to conduct part of the treatment at home. This can only be done with adequately trained personnel. In the Netherlands, specialized pediatric oncology home care nurse practitioners have been trained to deliver this kind of care. Therefore, a pilot study was conducted to administer intravenous chemotherapy at home. PURPOSE: This study aimed to safely administer chemotherapy intravenously (iv) at home by specialized nurse practitioners and aimed to increase the quality of life (QOL) of the child and decrease the social burden in families with a child with acute lymphoblastic leukemia (ALL). METHOD: The pilot study was performed by well-trained home care nurse practitioners. Low-dose methotrexate iv and low-dose cytarabine iv were administered to 11 included children with ALL in their home environment. RESULTS: QOL increased whereas social burden decreased for patients and parents. Chemotherapy administration in the home environment was safe with the help of well-trained nurse practitioners. CONCLUSION: It is feasible to administer intravenous chemotherapy at home in a safe and efficient way. The role of the specialized pediatric oncology nurse practitioner is an essential one.

Asparaginase inhibits the lectin pathway of complement activation.

Oncological treatment has been associated with an increased risk of infection, most often related to therapy-induced pancytopenia. However, limited research has been conducted on the effect of oncological therapy on the complement system, being part of the non-cellular innate immune system. This became the rationale for an observational clinical study (C2012) in which we have investigated the prevalence of transient complement defects. Once we had observed such defects, a correlation of the complement defects to specific clinical parameters or to specific therapeutic regimens was investigated. A prominent defect observed in C2012 was the inhibition of the lectin pathway (LP) of complement activation during the treatment of acute lymphoblastic leukemia (ALL), which we could directly associate to the use of asparaginase (ASNase). Ex-vivo experiments confirmed a direct dose-dependent inhibitory effect of ASNase on the LP functionality.

Development of the testis in pre-pubertal boys with cancer after biopsy for fertility preservation.

STUDY QUESTION: Is testicular growth affected by a testicular biopsy intended for fertility preservation in pre-pubertal boys with cancer? SUMMARY ANSWER: Testicular growth of the biopsied testis is not impeded in comparison to the non-biopsied contralateral testis up until 1 year after surgery. WHAT IS KNOWN ALREADY: Fertility preservation in pre-pubertal boys by means of testicular biopsy has been conducted for more than 15 years. Although immediate adverse effects of testicular biopsy are rare (1%), no data exist on the effect of biopsy on testicular growth. STUDY DESIGN, SIZE, DURATION: In this prospective cohort study, between March 2011 and February 2017, 93 parents of pre-pubertal boys were offered cryopreservation of testicular tissue of their son, of whom 78 consented. Sixty-four boys were included in this follow-up study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All boys with cancer at the paediatric oncology department of the Academic Medical Center (AMC) who needed gonadotoxic therapy and were unable to ejaculate were offered cryopreservation of testicular tissue prior to treatment. By testicular ultrasound before and after biopsy (1, 6 and 12 months after biopsy), volume and parenchymal abnormalities were assessed. Data were analysed using mixed-effects modelling. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 64 included boys all were followed up at 1 month, 58 at 6 months and 55 at 12 months. Mean testicular volumes after 1, 6 and 12 months after biopsy were 1.7 ± 2.1, 1.7 ± 2.2 and 1.9 ± 2.4 for the biopsied testis and 1.8 ± 2.2, 1.8 ± 2.3 and 2.0 ± 2.2 for the non-biopsied testis, respectively. Biopsy of the testis did not have a significant impact on testicular growth. Immediate adverse effects of the biopsy, i.e. wound infections, were seen in 3/78 boys (3.8%). LIMITATIONS, REASONS FOR CAUTION: Although it is the largest cohort available to date, the number of patients included in our follow-up is still relatively small. A larger cohort would be able to evaluate growth more precisely. Follow-up was discontinued in a significant portion of boys, 12/76 (15.8%), mainly because of death due to primary illness but also because they could not be reached or declined further follow-up. WIDER IMPLICATIONS OF THE FINDINGS: These reassuring data may be used in counselling future boys who are eligible for fertility preservation and their parents. STUDY FUNDING/COMPETING INTEREST(S): Study funded by KIKA Foundation (Kika 86), Grant from the Netherlands Organisation for Health Research and Development (ZonMW TAS-116003002). The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER: CCMO-register: NL27690.000.09.

Patients' and parents' views regarding supportive care in childhood cancer.

PURPOSE: Intensive therapies in pediatric malignancies increased survival rates but also occurrence of treatment-related morbidities. Therefore, supportive care fulfills an increasingly important role. In planning development of guidelines with incorporation of shared decision making, we noticed that little is known about the needs and preferences of patients and their parents. Our goals were therefore to investigate (1) which supportive care topics patients and parents regard as most important and (2) the preferred role they wish to fulfill in decision making. METHODS: This qualitative study consisted of three focus groups (two traditional, one online) with patients and parents of two Dutch pediatric oncology centers. Data were transcribed as simple verbatim and analyzed using thematic analysis. RESULTS: Eleven adolescent patients and 18 parents shared detailed views on various aspects of supportive care. Themes of major importance were communication between patient and physician (commitment, accessibility, proactive attitude of physicians), well-timed provision of information, and the suitability and accessibility of psychosocial care. In contrast to prioritized supportive care topics by medical professionals, somatic issues (e.g., febrile neutropenia) were infrequently addressed. Patients and parents preferred to be actively involved in decision making in selected topics, such as choice of analgesics and anti-emetics, but not in, e.g., choice of antibiotics. CONCLUSIONS: Children with cancer and parents were provided a valuable insight into their views regarding supportive care and shared decision making. These results have important implications towards improving supportive care, both in selecting topics for guideline development and incorporating preferences of patients and parents herein.

Towards culturally competent paediatric oncology care. A qualitative study from the perspective of care providers.

In order to gain more insight on the influence of ethnic diversity in paediatric cancer care, the perspectives of care providers were explored. Semi-structured interviews were conducted among 12 paediatric oncologists and 13 nurses of two different paediatric oncology wards and were analysed using a framework method. We found that care providers described the contact with Turkish and Moroccan parents as more difficult. They offered two reasons for this: (1) language barriers between care provider and parents hindered the exchange of information; (2) cultural barriers between care provider and parents about sharing the diagnosis and palliative perspective hindered communication. Care providers reported different solutions to deal with these barriers, such as using an interpreter and improving their cultural knowledge about their patients. They, however, were not using interpreters sufficiently and were unaware of the importance of eliciting parents' perspectives. Communication techniques to overcome dilemmas between parents and care providers were not used and care providers were unaware of stereotypes and prejudice. Care providers should be offered insight in cultural barriers they are unaware of. Training in cultural competence might be a possibility to overcome manifest barriers.

The importance of evidence-based supportive care practice guidelines in childhood cancer-a plea for their development and implementation.

As cure rates in pediatric oncology have improved substantially over the last decades, supportive care has become increasingly important to reduce morbidity and mortality and improve quality of life in children with cancer. Currently, large variations exist in pediatric oncology supportive care practice, which might negatively influence care. This plea underlines the importance of development and implementation of trustworthy supportive care clinical practice guidelines, which we believe is the essential next step towards better supportive care practice, and thus a higher quality of care. To facilitate international development and endorsement, the International Pediatric Oncology Guidelines in Supportive Care Network has been established.

Stem cell CD44v isoforms promote intestinal cancer formation in Apc(min) mice downstream of Wnt signaling.

A gene signature specific for intestinal stem cells (ISCs) has recently been shown to predict relapse in colorectal cancer (CRC) but the tumorigenic role of individual signature genes remains poorly defined. A prominent ISC-signature gene is the cancer stem cell marker CD44, which encodes various splice variants comprising a diverse repertoire of adhesion and signaling molecules. Using Lgr5 as ISC marker, we have fluorescence-activated cell sorting-purified ISCs to define their CD44 repertoire. ISCs display a specific set of CD44 variant isoforms (CD44v), but remarkably lack the CD44 standard (CD44s) isoform. These CD44v also stand-out in transformed human ISCs isolated from microadenomas of familial adenomatous polyposis patients. By employing knock-in mice expressing either CD44v4-10 or CD44s, we demonstrate that the CD44v isoform, but not CD44s, promotes adenoma initiation in Apc(Min/+)mice. Our data identify CD44v as component of the ISCs program critical for tumor initiation, and as potential treatment target in CRC.

A novel method for evaluating natural and vaccine induced serological responses to Bordetella pertussis antigens.

We studied the time course of serum IgG antibodies against 3 different pertussis vaccine antigens: PT (pertussis toxin), FHA (filamentous hemagglutinin), Prn (pertactin) in sera from individuals vaccinated with four different pertussis vaccines at 4 years of age: (N=44, 44, 23 and 23, respectively,) and compared the responses to/after natural infection with Bordetella pertussis (N=44, age 1-8 years). These longitudinal data were analyzed with a novel method, using a mathematical model to describe the observed responses, and their variation among subjects. This allowed us to estimate biologically meaningful characteristics of the serum antibody response, like peak level and decay rate, and to compare these among natural infections and vaccine responses. Compared to natural infection, responses to PT after vaccination with the tested vaccines are smaller in magnitude and tend to decay slightly faster. When present in vaccines, FHA and Prn tend to produce high peak levels, higher than those in naturally infected patients, but these decay faster. As expected, the Dutch whole cell vaccine produced lower antibody responses than the acellular vaccines. This model allows a better comparison of the kinetics of vaccine induced antibody responses and after natural infection over a long follow up period.

Accrual in supportive care trials in pediatric oncology, a challenge!

PURPOSE: Treatment protocols in pediatric oncology have historically known high accrual rates, up to 94 %. Accrual for supportive care studies on the other hand appears to be a challenge. The aim of this study was to search for reasons explaining this poor accrual and for possible interventions to improve patient enrolment. METHODS: The failure screen log of our supportive care study (the Aristocaths study) was analyzed, and subsequently, a literature search was performed. RESULTS: The literature search (1985-2011) revealed three factors that can influence accrual. Firstly, study implementation and patient enrolment can be facilitated by appointing a dedicated clinical investigator in all participating centers and by facilitating clinical research nurses. Furthermore, adequate and tailor-made information is required for families to make a well-informed decision regarding study participation. Lastly, sufficient time should be assured for the process of decision making, especially since the number of eligible studies is increasing rapidly. Concerning our study, all three elements were met, but the most striking finding was the presumed burden of study participation by the majority of parents (82 %) as the main argument against randomization. CONCLUSIONS: Accrual of pediatric oncology patients in supportive care studies is challenging. Nevertheless, well-designed randomized controlled trials in supportive care will be essential for the improvement of pediatric cancer care. Therefore, we will need to increase awareness through (inter)national supportive care working groups regarding the need for supportive care trials and stimulate accrual when such trials are open.

Mannose-binding lectin (MBL) and the risk for febrile neutropenia and infection in pediatric oncology patients with chemotherapy.

BACKGROUND: We determined whether mannose-binding lectin (MBL) deficiency is associated with an increased risk of febrile neutropenia (FN) and/or infection in pediatric oncology patients. PROCEDURE: We systematically searched and reviewed all the literature on MBL and infections in children with cancer, identified from a literature search of Medline, Embase, and Central (1966-April 2010). We extracted information on the type of study, patient characteristics, definition of MBL deficiency, definition of infection and method of detection, follow-up period and the results of the outcome in different groups. The validity of each study was assessed. RESULTS: Six cohort studies were retrieved, consisting of 581 children with leukemia (n = 2) or varying types of cancer (n = 4). Many different outcome definitions were used. In only one out of three genotype studies, variant MBL2 genotypes, as well as MBL levels < 1,000 µg/L, were associated with an increased duration of FN. In one additional MBL level study the number of FN episodes, bacteremia and severe bacterial infection were increased in patients with MBL levels < 100 µg/L as compared to those with MBL levels of 100-999 µg/L. Sepsis, pneumonia, viral infection, and fungal infection were not associated with either MBL levels or genotypes in any of the studies. CONCLUSIONS: MBL deficiency could not be identified as an independent risk factor for FN or infection in pediatric oncology patients. A multicenter study of children with comparable chemotherapy regimens, relevant and equal outcome definitions and measuring both MBL levels and genotypes, will be required to avoid clinical and methodological inconsistencies.

Mannose-binding lectin (MBL) as prognostic factor in paediatric oncology patients.

Deficiency of mannose-binding lectin (MBL) has been suggested to influence duration of febrile neutropenia and prognosis in paediatric oncology patients. However, there is no consensus on the definition of MBL deficiency. In a cohort of children with cancer, we investigated (i) how to determine MBL deficiency and (ii) whether MBL is a prognostic factor for disease severity. In 222 paediatric oncology patients, 92 healthy children and 194 healthy adults, MBL plasma levels and MBL2 genotype (wild-type: A, variant: O) were determined. Event-free survival (EFS), overall survival (OS) and paediatric intensive care unit (PICU) admissions were recorded prospectively. In febrile neutropenic patients admitted to the PICU, disease severity was assessed by clinical, microbiological and laboratory parameters. An optimal cut-off value for MBL deficiency was determined to be < 0·20 µg/ml. Wild-type MBL2 genotype patients, including the XA/XA haplotype, had increased MBL levels compared to healthy individuals. MBL deficiency was associated with decreased EFS (P = 0·03), but not with need for PICU admission. A trend for a twice increased frequency of septic shock (80% versus 38%, P = 0·14), multiple organ failure (40% versus 17%, P = 0·27) and death (40% versus 21%, P = 0·27) was observed in the absence of microbiological findings. MBL deficiency was associated with decreased EFS and possibly with an increased severity of disease during PICU admission after febrile neutropenia in the absence of any association with microbiological findings. These findings suggest prognosis to be worse in MBL-deficient compared to MBL-sufficient paediatric oncology patients.

Health-related quality of life after completion of successful treatment for childhood cancer.

BACKGROUND: Previous studies have assessed health-related quality of life (HRQOL) during several treatment stages in children with cancer, but there is limited knowledge about HRQOL shortly after completing therapy. This study determined HRQOL of children with cancer shortly after the end of successful treatment compared with normative values. PROCEDURE: Several age-specific HRQOL questionnaires were administered: the ITQOL (generic, proxy-report, 0-4 years), CHQ PF 50 (generic, proxy-report, 5-7 years), Kidscreen (generic, self-report, 8-18 years) and Disabkids (chronic generic, self-report, 8-18 years). RESULTS: Children with cancer (N = 191, mean age 9.25, SD 5.06, 47.1% female) participated. Physical well-being was affected for all ages. Compared to normative values 0- to 7-year-olds were rated significantly lower on the majority of the scales. In addition, 12- to 18-year-olds had significantly better HRQOL than the norm on social scales. Compared to chronically ill norms, 8- to 18-year-olds demonstrated no differences, except for 12- to 18-year-olds who experienced significantly more physical limitations. Additionally, we found that HRQOL of parents of 0- to 7-year-olds was poorer than the norm. CONCLUSION: HRQOL in children with cancer and their parents can be impaired compared with the norm. Therefore, HRQOL should be monitored in clinical practice to make paediatric oncologists aware of these problems. For young children, we recommend checking whether certain HRQOL problems can be explained by parental worries. For older children and adolescents, paediatric oncologists need to consider social desirability and the child's adaptive style.

Gastric adenocarcinoma in a 13-year-old boy: a diagnosis not often seen in this age group.

Gastric adenocarcinoma is not uncommon in the adult population, but in the pediatric population it is an extremely rare entity. A 13-year-old boy was referred to a pediatric oncology unit for evaluation of a tumor in the upper abdomen. Further investigation revealed an advanced stage gastric carcinoma with metastases suggestive for a hereditary cause. Awareness for uncommon diagnoses is a key issue in regard of accurate treatment and overall prognosis.

Mannose-binding lectin and infection risk in newborns: a systematic review.

The authors systematically reviewed the literature on mannose-binding lectin (MBL) and infections in newborns to determine whether infection risk is increased in MBL-deficient newborns. All original reports on MBL and infections in newborns were retrieved from Embase, Medline and CENTRAL from 1966 to December 2009. Information extracted from each article included study design, definitions of MBL deficiency and neonatal infection, follow-up period and risk factor analysis. The validity of each study was assessed. Eight prospective cohort studies, including 3166 (range 47-1832) premature or term neonates, were assessed. MBL levels were measured in five studies and MBL2 genotype in six studies. Definitions of MBL deficiency and infection varied. In three out of five phenotypic studies low MBL levels were statistically significantly associated with increased culture-confirmed sepsis rates, also after correction for gestational age or birth weight. In the first study, the median MBL level was decreased in newborns with confirmed sepsis (170 µg/l) compared with newborns without sepsis (1450 µg/l). In two other studies, culture-confirmed sepsis was associated with MBL levels ≤700 µg/l (OR 15.0, 95% CI 1.5 to 151.3) and ≤400 µg/l (OR 3.1), respectively. The remaining two studies investigated various non-culture-confirmed infections. Only one study included the timepoint of clinical suspicion of infection in multivariate analysis. Contradicting results were reported in six MBL2 genotypic studies. Newborns with low MBL levels appear to have culture-confirmed sepsis more frequently than MBL-sufficient newborns. However, the influence of confounding factors was analysed insufficiently. Variant MBL2 genotypes appear to have less influence.

[Influenza in children undergoing chemotherapy]. / Influenza bij kinderen die chemotherapie ondergaan.

Two paediatric cancer patients were found to have influenza shortly after receiving chemotherapy. Both presented with neutropenic fever. The first patient, a 15-year-old boy with Hodgkin's lymphoma, recovered without complications. The second patient, a 15-month-old-girl with metastatic Wilms' tumour, died due to severe infectious complications. These cases illustrate that common viruses, such as the influenza virus, can cause fulminant secondary infections in immunocompromised patients. Viruses, including the influenza virus, should always be considered as pathogens in patients with neutropenic fever, and influenza vaccination should be considered in these high-risk patients.

Granulocyte transfusions in neutropaenic children: a systematic review of the literature.

BACKGROUND: Granulocyte transfusions (GTX) have been used for decades in paediatric neutropaenic patients, but uncertainty remains regarding their effectiveness. We reviewed all the paediatric data available on GTX, to gain a insight in to the indications for use, favourable effects and side effects in patients and donors. METHODS: A comprehensive search was done in MEDLINE, EMBASE, LILACS and CENTRAL (1966 until 2006). All studies including children (1-18 years) who received GTX were included. RESULTS: A total of 66 observational studies were included:Seven using prophylactic and 59 therapeutic GTX. Of the therapeutic studies 55 reported a proven sepsis caused by Gram-negative bacteria (34%) or fungal disease (48%) as the indication for GTX. Concerning effectiveness 70% survival was reported, but no controlled studies were identified. Side effects were mentioned in 27 studies including mild respiratory symptoms, allergic reactions and infection related complications (CMV). Side effects in the donor were mainly flu-like illness. DISCUSSION: In this first review covering 30 years of experience on the use of GTX in children, we found no randomised evidence showing a positive benefit risk ratio. The available case reports and cohort studies alert us as to the potential benefits and harms of the use of GTX in neutropaenic children and provides the basis for a well designed trial in children.