Pediatric open long-bone fracture and subsequent deep infection risk: The importance of early hospital care

The purpose of the current study was to identify risk factors for deep infection after an open long-bone fracture in pediatric patients. Systematic billing queries were utilized to identify pediatric patients who presented to a level I trauma center from 1998 to 2019 with open long-bone fractures. There were 303 open long-bone fractures, and 24 (7.9%) of these became infected. Fractures of the tibia/fibula

CARbon DIoxide for the treatment of Febrile seizures: rationale, feasibility, and design of the CARDIF-study

Background: 2-8% of all children aged between 6 months and 5 years have febrile seizures. Often these seizures cease spontaneously, however depending on different national guidelines, 20-40% of the patients would need therapeutic intervention. For seizures longer than 3-5 minutes application of rectal diazepam, buccal midazolam or sublingual lorazepam is recommended. Benzodiazepines may be ineffective in some patients or cause prolonged sedation and fatigue. Preclinical investigations in a rat model provided evidence that febrile seizures may be triggered by respiratory alkalosis, which was subsequently confirmed by a retrospective clinical observation. Further, individual therapeutic interventions demonstrated that a pCO2-elevation via re-breathing or inhalation of 5% CO2 instantly stopped the febrile seizures. Here, we present the protocol for an interventional clinical trial to test the hypothesis that the application of 5% CO2 is effective and safe to suppress febrile seizures in children. Methods: The CARDIF (CARbon DIoxide against Febrile seizures) trial is a monocentric, prospective, double-blind, placebo-controlled, randomized study. A total of 288 patients with a life history of at least one febrile seizure will be randomized to receive either carbogen (5% CO2 plus 95% O2) or placebo (100% O2). As recurrences of febrile seizures mainly occur at home, the study medication will be administered by the parents through a low-pressure can fitted with a respiratory mask. The primary outcome measure is the efficacy of carbogen to interrupt febrile seizures. As secondary outcome parameters we assess safety, practicability to use the can, quality of life, contentedness, anxiousness and mobility of the parents. Prospect: The CARDIF trial has the potential to develop a new therapy for the suppression of febrile seizures by redressing the normal physiological state. This would offer an alternative to the currently suggested treatment with benzodiazepines. This study is an example of academic translational research from the study of animal physiology to a new therapy

FCET2EC (From controlled experimental trial to = 2 everyday communication): How effective is intensive integrative therapy for stroke-induced chronic aphasia under routine clinical conditions? A study protocol for a randomized controlled trial

Background: Therapy guidelines recommend speech and language therapy (SLT) as the “gold standard” for aphasia treatment. Treatment intensity (i.e., ≥5 hours of SLT per week) is a key predictor of SLT outcome. The scientific evidence to support the efficacy of SLT is unsatisfactory to date given the lack of randomized controlled trials (RCT), particularly with respect to chronic aphasia (lasting for >6 months after initial stroke). This randomized waiting list-controlled multi-centre trial examines whether intensive integrative language therapy provided in routine in- and outpatient clinical settings is effective in improving everyday communication in chronic post-stroke aphasia. Methods/Design: Participants are men and women aged 18 to 70 years, at least 6 months post an ischemic or haemorrhagic stroke resulting in persisting language impairment (i.e., chronic aphasia); 220 patients will be screened for participation, with the goal of including at least 126 patients during the 26-month recruitment period. Basic language production and comprehension abilities need to be preserved (as assessed by the Aachen Aphasia Test).Therapy consists of language-systematic and communicative-pragmatic exercises for at least 2 hours/day and at least 10 hours/week, plus at least 1 hour self-administered training per day, for at least three weeks. Contents of therapy are adapted to patients’ individual impairment profiles.Prior to and immediately following the therapy/waiting period, patients’ individual language abilities are assessed via primary and secondary outcome measures. The primary (blinded) outcome measure is the A-scale (informational content, or 'understandability’, of the message) of the Amsterdam-Nijmegen Everyday Language Test (ANELT), a standardized measure of functional communication ability. Secondary (unblinded) outcome measures are language-systematic and communicative-pragmatic language screenings and questionnaires assessing life quality as viewed by the patient as well as a relative.The primary analysis tests for differences between the therapy group and an untreated (waiting list) control group with respect to pre- versus post 3-week-therapy (or waiting period, respectively) scores on the ANELT A-scale. Statistical between-group comparisons of primary and secondary outcome measures will be conducted in intention-to-treat analyses. Long-term stability of treatment effects will be assessed six months post intensive SLT (primary and secondary endpoints)

Phase II trial of temsirolimus for relapsed/refractory primary CNS lymphoma

Purpose: In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and Methods: Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week. Results: Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF. Conclusion: Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived

Regeneração medular: a ação do neurotrophin-3 sobre a lesão medular de ratos

OBJECTIVE: For many years, it was believed that medullary regeneration could not occur, although currently there are many trials using neurotrophic factors, stem cells, fetal medulla grafts, peripheral nerve grafts, and antibodies against myelin-associated proteins that demonstrate the existence of the possibility of spinal cord regeneration. The purpose of this study was to investigate the action of neurotrophin-3, a novel neurotrophic factor. METHODS: The New York University impactor, a standardized device for delivery of spinal cord injuries was used on 33 rats, which were divided into 2 groups: a control group receiving distilled water intraperitoneally and a treatment group receiving neurotrophin-3 intraperitoneally. RESULTS: Using the Basso, Beattie, and Bresnahan scale, the locomotor recovery curve for the neurotrophin-3 treated group was superior to that of the control group (P < 0.05); the administration of neurotrophin-3 was associated with the absence of deaths, while the control group showed a 28.5% (P = 0.026) mortality rate. Other parameters (hematuria rate and histological analysis) showed no significant differences. CONCLUSIONS: Based on these results, it appears that a strong relationship exists between the use of neurotrophin-3 in rats with spinal cord injury and better functional recovery.OBJETIVO: Por muitos anos acreditou-se que a regeneração medular não fosse factível. Atualmente porém, existem várias experiências utilizando fatores neurotróficos, células troncos, enxerto de medula fetal, enxerto de nervo periférico e anticorpos contra proteínas associadas a mielina que sugerem o contrário. Esta pesquisa estudou a ação de um dos mais novos neurotróficos, o Neurotrophin-3. MÉTODOS: As lesões medulares foram realizadas através do New York University impator, método experimental de produção de lesão medular padronizada. Foram utilizados 33 ratos divididos em 2 grupos. Um grupo controle com administração intraperitoneal de água destilada e um grupo tratamento, tratado com Neurotrophin-3 por via intraperitoneal. RESULTADOS: Observamos que a curva de recuperação locomotora, segundo a escala de Basso, Beattie e Bresnahan, do grupo Neurotrophin-3 foi superior à do grupo controle (p < 0,05); a administração de Neurotrophin-3 determinou ausência de mortes no grupo tratamento, enquanto o grupo controle apresentou taxa de mortalidade de 28,5% (p = 0,026). Os outros parâmetros (taxa de hematúria e análise histológica) não apresentaram diferenças estatisticamente significantes. CONCLUSÕES: Existe forte relação entre a aplicação de Neurotrophin-3 em ratos com lesão medular e melhor recuperação funcional

Mode of action-based risk assessment of genotoxic carcinogens

The risk assessment of chemical carcinogens is one major task in toxicology. Even though exposure has been mitigated effectively during the last decades, low levels of carcinogenic substances in food and at the workplace are still present and often not completely avoidable. The distinction between genotoxic and non-genotoxic carcinogens has traditionally been regarded as particularly relevant for risk assessment, with the assumption of the existence of no-effect concentrations (threshold levels) in case of the latter group. In contrast, genotoxic carcinogens, their metabolic precursors and DNA reactive metabolites are considered to represent risk factors at all concentrations since even one or a few DNA lesions may in principle result in mutations and, thus, increase tumour risk. Within the current document, an updated risk evaluation for genotoxic carcinogens is proposed, based on mechanistic knowledge regarding the substance (group) under investigation, and taking into account recent improvements in analytical techniques used to quantify DNA lesions and mutations as well as “omics” approaches. Furthermore, wherever possible and appropriate, special attention is given to the integration of background levels of the same or comparable DNA lesions. Within part A, fundamental considerations highlight the terms hazard and risk with respect to DNA reactivity of genotoxic agents, as compared to non-genotoxic agents. Also, current methodologies used in genetic toxicology as well as in dosimetry of exposure are described. Special focus is given on the elucidation of modes of action (MOA) and on the relation between DNA damage and cancer risk. Part B addresses specific examples of genotoxic carcinogens, including those humans are exposed to exogenously and endogenously, such as formaldehyde, acetaldehyde and the corresponding alcohols as well as some alkylating agents, ethylene oxide, and acrylamide, but also examples resulting from exogenous sources like aflatoxin B$_{1}$, allylalkoxybenzenes, 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), benzo[a]pyrene and pyrrolizidine alkaloids. Additionally, special attention is given to some carcinogenic metal compounds, which are considered indirect genotoxins, by accelerating mutagenicity via interactions with the cellular response to DNA damage even at low exposure conditions. Part C finally encompasses conclusions and perspectives, suggesting a refined strategy for the assessment of the carcinogenic risk associated with an exposure to genotoxic compounds and addressing research needs

Variability of disk emission in pre-main sequence and related stars. II. Variability in the gas and dust emission of the Herbig Fe star SAO 206462

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.We present 13 epochs of near-infrared (0.8-5 μm) spectroscopic observations of the pre-transitional, "gapped" disk system in SAO 206462 (=HD 135344B). In all, six gas emission lines (Brα, Brγ, Paβ, Paγ, Paδ, Paepsilon, and the 0.8446 μm line of O I) along with continuum measurements made near the standard J, H, K, and L photometric bands were measured. A mass accretion rate of approximately 2 × 10–8 M ☉ yr–1 was derived from the Brγ and Paβ lines. However, the fluxes of these lines varied by a factor of over two during the course of a few months. The continuum also varied, but by only ~30%, and even decreased at a time when the gas emission was increasing. The H I line at 1.083 μm was also found to vary in a manner inconsistent with that of either the hydrogen lines or the dust. Both the gas and dust variabilities indicate significant changes in the region of the inner gas and the inner dust belt that may be common to many young disk systems. If planets are responsible for defining the inner edge of the gap, they could interact with the material on timescales commensurate with what is observed for the variations in the dust, while other disk instabilities (thermal, magnetorotational) would operate there on longer timescales than we observe for the inner dust belt. For SAO 206462, the orbital period would likely be 1-3 years. If the changes are being induced in the disk material closer to the star than the gap, a variety of mechanisms (disk instabilities, interactions via planets) might be responsible for the changes seen. The He I feature is most likely due to a wind whose orientation changes with respect to the observer on timescales of a day or less. To further constrain the origin of the gas and dust emission will require multiple spectroscopic and interferometric observations on both shorter and longer timescales that have been sampled so far.This work was supported by NASA ADP grants NNH06CC28C and NNX09AC73G, Hubble Space Telescope grants HST-GO-10764 and HST-GO-10864, Chilean National TAC grants CNTAC-010A-064

malaria infection among schoolchildren in highland Rwanda

Background Plasmodium infection and malaria in school children are increasingly recognized as a relevant public health problem, but data on actual prevalence and health consequences are insufficient. The present study from highland southern Rwanda aimed at estimating infection prevalence among children attending school, at identifying associated factors and at assessing the clinical consequences of these infections. Methods In a survey including 12 schools in the Huye district of Rwanda, 1089 children aged 6–10 years were clinically and anthropometrically examined, malaria parasites were diagnosed by microscopy and PCR, haemoglobin concentrations were measured, and socio- economic and behavioural parameters as well as medical histories were obtained. Results Upon examination, the vast majority of children was asymptomatic (fever 2.7%). Plasmodium infection was detected in 22.4% (Plasmodium falciparum, 18.8%); 41% of these were submicroscopic. Independent predictors of infection included low altitude, higher age, preceding antimalarial treatment, and absence of electricity or a bicycle in the household. Plasmodium infection was associated with anaemia (mean haemoglobin difference of −1.2 g/dL; 95% CI, −0.8 to −1.5 g/dL), fever, underweight, clinically assessed malnutrition and histories of fever, tiredness, weakness, poor appetite, abdominal pain, and vomiting. With the exception of underweight, these conditions were also increased at submicroscopic infection. Conclusion Malaria infection is frequent among children attending school in southern highland Rwanda. Although seemingly asymptomatic in the vast majority of cases, infection is associated with a number of non-specific symptoms in the children´s histories, in addition to the impact on anaemia. This argues for improved malaria surveillance and control activities among school children