Topical curcumin can inhibit deleterious effects of upper respiratory tract bacteria on human oropharyngeal cells in vitro: potential role for patients with cancer therapy induced mucositis?

Curcumin exerts its anti-inflammatory activity via inhibition of nuclear factor κB. Oropharyngeal epithelia and residing bacteria closely interact in inflammation and infection. This in vitro model investigated the effects of curcumin on bacterial survival, adherence to, and invasion of upper respiratory tract epithelia, and studied its anti-inflammatory effect. We aimed to establish a model, which could offer insights into the host-pathogen interaction in cancer therapy induced mucositis.

Posaconazole salvage treatment in paediatric patients: a multicentre survey

While a paediatric dosage has not been defined, posaconazole is occasionally being used in children. We conducted a multicentre retrospective survey and identified 15 patients (median age 10 years [range 3.6-17.5]) who received posaconazole salvage therapy for proven (9 patients) or probable (6 patients) invasive fungal infections. Posaconazole was administered for a median of 32 days (range 4-262) at a median dosage of 21 mg/kg (range 4.8-33.3). None of the patients discontinued therapy due to adverse events, which were mostly mild and observed in 11 patients. Complete or partial responses were observed in 4/7 patients with zygomycosis, 3/4 patients with invasive mould infection, 1/2 patients with invasive aspergillosis and 1/2 patients with chronic disseminated candidiasis. We conclude from the data that posaconazole displays favourable safety and tolerance and may be useful for management of individual paediatric patients with invasive infections.

Voriconazole-induced phototoxicity in children

Voriconazole is used in antifungal prophylaxis. We performed a retrospective review of immunocompromised children receiving prophylaxis with voriconazole during major hospital renovation, who developed phototoxic skin reactions. The overall incidence of phototoxic skin reactions was 33%. A voriconazole dose of ≥6 mg/kg of body weight per dose twice daily was associated with a significantly greater risk to develop phototoxic skin reactions compared with lower doses.

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.

Clinicopathologic features and long-term outcomes of NUT midline carcinoma

NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.

Treatment of intestinal and hepatic mucormycosis in an immunocompromized child

During ALL chemotherapy, a 4-year-old patient presented with febrile neutropenia and abdominal pain. Ultrasound examinations were repeatedly normal. Computerized tomography on day 7 demonstrated appendicitis and multiple hepatic foci identified as mucormycosis (Absidia corymbifera). Successful outcome was achieved by aggressive re-surgery, long-term antifungal therapy with serum level-monitored posaconazole, and recovery of neutrophil counts. Considering the interference of posaconazole with CYP3A4, vincristine was administered during 72 hr posaconazole windows. Pediatric intestinal mucormycosis, still associated with a >70% case-fatality rate, calls for early imaging and surgery to establish the diagnosis, reduce the fungal mass, and provide a rationale for using posaconazole.

Non-classical karyotypic features in relapsed childhood B-cell precursor acute lymphoblastic leukemia

Karyotype analysis of acute lymphoblastic leukemia (ALL) at diagnosis has provided valuable prognostic markers for treatment stratification. However, reports of cytogenetic studies of relapsed ALL samples are limited. We compared the karyotypes from 436 nonselected B-cell precursor ALL patients at initial diagnosis and of 76 patients at first relapse. We noticed a relative increase of karyotypes that did not fall into the classic ALL cytogenetic subgroups (high hyperdiploidy, t(12;21), t(9;22), 11q23, t(1;19), <45 chromosomes) in a group of 29 patients at relapse (38%) compared to 130 patients at presentation (30%). Non-classical cytogenetic aberrations in these 29 patients were mostly found on chromosomes 1, 2, 7, 9, 13, 14, and 17. We also describe six rare reciprocal translocations, three of which involved 14q32. The most frequent abnormalities were found in 9p (12/29 cases) and were associated with a marked decrease in the duration of the second remission, but not of the probability of 10-year event-free survival after relapse treatment. From 29 patients with non-classical cytogenetic aberrations, only 8 (28%) had been stratified to a high risk-arm on the first treatment protocol, suggesting that this subgroup might benefit from the identification of new prognostic markers in future studies.

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-kappaB 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.

Health-related quality of life in young survivors of childhood cancer

PURPOSE Childhood cancer and its treatment may affect health-related quality of life (HRQoL) in childhood cancer survivors, but population-based studies in young survivors are scarce. We aimed to: (1) compare HRQoL between young survivors and population norms and (2) find factors that influence parent-reported HRQoL in survivors. METHODS As part of the Swiss Childhood Cancer Survivor Study, a questionnaire was mailed to parents of survivors aged 8-16 years, registered in the Swiss Childhood Cancer Registry, ≥5 years after diagnosis. We used the KIDSCREEN-27 instrument to compare self- and parent-reported HRQoL between survivors (N = 425) and standardized norms in the five dimensions of physical well-being, psychological well-being, autonomy, peers and school environment (mean = 50, SD = 10). We then used multivariable linear regressions to test the influence of socio-demographic and cancer-related factors on HRQoL. RESULTS Self-reported physical well-being was comparable to norms. Other HRQoL dimensions were higher than norms, with the highest mean = 52.2 (p < 0.001) for school environment. Parent-reported HRQoL in survivors was comparable to population norms; only physical well-being was lower (mean = 47.1, p < 0.001), and school environment was higher (mean = 51.1, p = 0.035). Parent-reported HRQoL was lower for survivors of CNS tumors (physical well-being: β = -5.27, p = 0.007; psychological well-being: β = -4.39, p = 0.044; peers β = -5.17, p = 0.028), survivors of neuroblastoma (psychological well-being β = -5.20, p = 0.047), and survivors who had had a relapse (physical well-being β = -5.41, p = 0.005). CONCLUSIONS Assessing HRQoL during follow-up care, with a focus on physical well-being, specific diagnoses (e.g., CNS tumor) and late complications (e.g., relapse) might help to early identify problems and offer support to survivors with reduced HRQoL.

Einfluss des Trampolinsprungtuchs und der Sprunghöhe auf die Vertikalbeschleunigung an der Brustwirbelsäule

Die 2011 für das Trampolinturnen eingeführte, instrumentierte Bewertung der Sprunghöhe hatte die Entwicklung wurfstärkerer Sprungtücher und damit eine Zunahme der Sprunghöhen zur Folge. Inwieweit dabei die Beanspruchung des Bewegungsapparates gestiegen ist, wird durch vergleichende biomechanische Analysen verschiedener Sprünge von Athlet/innen des deutschen Nationalkaders auf dem alten 6x4- und dem neuen 4x4 -Sprungtuch untersucht. Erste Analysen zeigten, dass sich die Zunahme der Sprunghöhe auf dem 4x4-Tuch notwendigerweise in einem größeren Kraftstoß begründet, dieser aber nicht durch eine längere Tuchkontaktzeit, sondern durch eine höhere Kraft zustande kommt (Kredel, Eisele, Schweizer, Kuhn & Riehle, 2014). In der Folge soll nun der Einfluss dieser Kraftzunahme auf Bewegungsparameter und Beanspruchung untersucht werden. Kinematische Merkmale von Körper- und Wirbelsäulensegmenten wurden mit einem Vicon-T40s-System aufgezeichnet, während die Bodenreaktionskraftverläufe mit vier Kis t-ler-Kraftmessplatten erfasst wurden. Eine individualisierte, inversdynamische Modellierung der Tuchkontaktphasen soll Aufschluss über die Beanspruchungsunterschiede relevanter Gelenksstrukturen (Sprung-, Knie-, Hüftgelenk, LWS, BWS) geben. Zur Modellvalidierung dient die mittels Beschleunigungssensor erfasste Brustwirbelsäulenkinematik, deren Ausprägung in Bezug zur Sprunghöhe Gegenstand des aktuellen Untersuchungsteils war. Analysen von 102 Standsprüngen zeigen Zusammenhänge zwischen der Sprunghöhe und sowohl der mittleren (4x4: r(44)=.90, p<.001; 6x4: r(54)=.83, p<.001), als auch der maximalen (4x4: r(44)=.65, p<.001; 6x4: r(54)=.80, p<.001) Vertikalbeschleunigung der Brus twirbelsäule während des Tuchkontakts. Sind die Beschleunigungswerte – und damit die Belastungen – im mittleren Sprunghöhenbereich in ähnlichen Größenordnungen, ist festzuhalten, dass die durch das 4x4-Tuch erreichbaren größeren Sprunghöhen nicht nur einen weiteren Anstieg der mittleren, sondern auch eine weitere Erhöhung der maximalen Vertikalbeschleunigung zur Folge haben (Maximum 4x4: 151.4 m/s2 vs. 6x4: 139.6 m/s2) und somit die Maximalbelastung der Athlet/innen zunimmt. Aktuell wird dieser Befund bei den komplexeren Sprungvarianten verifiziert und die Gelenksbeansp.ruchung modelliert

Cancer's positive flip side: posttraumatic growth after childhood cancer.

BACKGROUND Surviving childhood cancer may result in positive psychological changes called posttraumatic growth (PTG). Knowing about the possibility of positive changes may facilitate survivors' reintegration in daily life. We aimed to (1) describe PTG in Swiss childhood cancer survivors including the most and the least common PTG phenomena on the subscale and item levels and (2) determine factors associated with PTG. METHOD Within the Swiss Childhood Cancer Survivor Study (SCCSS), we sent two questionnaires to childhood cancer survivors registered in the Swiss Childhood Cancer Registry (SCCR). Eligible survivors were diagnosed after 1990 at age ≤16 years, survived ≥5 years, and were aged ≥18 years at the time the second questionnaire was sent. We included the Posttraumatic Growth Inventory (PTGI) to assess five areas of PTG. We investigated the association of PTG with socio-demographic characteristics, self-reported late effects, and psychological distress, which were assessed in the SCCSS and clinical variables extracted from the SCCR. We used descriptive statistics to describe PTG and linear regressions to investigate factors associated with PTG. RESULTS We assessed PTG in 309 childhood cancer survivors. Most individuals reported to have experienced some PTG. The most endorsed change occurred in "relation with others," the least in "spiritual change." PTG was significantly higher in survivors with older age at diagnosis (p = 0.001) and those with a longer duration of treatment (p = 0.042), while it was lower in male survivors (p = 0.003). CONCLUSIONS Supporting experiences of PTG during follow-up may help survivors successfully return to daily life.

Use of Complementary and Alternative Medicine in Children with Cancer: A Study at a Swiss University Hospital

Background Though complementary and alternative medicine (CAM) are frequently used by children and adolescents with cancer, there is little information on how and why they use it. This study examined prevalence and methods of CAM, the therapists who applied it, reasons for and against using CAM and its perceived effectiveness. Parent-perceived communication was also evaluated. Parents were asked if medical staff provided information on CAM to patients, if parents reported use of CAM to physicians, and what attitude they thought physicians had toward CAM. Study Design All childhood cancer patients treated at the University Children’s Hospital Bern between 2002–2011 were retrospectively surveyed about their use of CAM. Results Data was collected from 133 patients (response rate: 52%). Of those, 53% had used CAM (mostly classical homeopathy) and 25% of patients received information about CAM from medical staff. Those diagnosed more recently were more likely to be informed about CAM options. The most frequent reason for choosing CAM was that parents thought it wouldimprove the patient’s general condition. The most frequent reason for not using CAM was lack of information. Of those who used CAM, 87% perceived positive effects. Conclusions Since many pediatric oncology patients use CAM, patients’ needs should be addressed by open communication between families, treating oncologists and CAM therapists, which will allow parents to make informed and safe choices about using CAM.