Use of remote monitoring with continuous glucose monitoring in young children with Type 1 diabetes: the parents' perspective.

AIM: Remote monitoring with continuous glucose monitoring (CGM) in children with Type 1 diabetes mellitus has recently become available, but little is known about caregivers' experiences of its use, particularly in younger children. The aim of this study was to explore parents' everyday experiences of using this technology. METHODS: The parents of children with Type 1 diabetes diagnosed for > 1 year, aged 2-12 years were invited to participate in a semi-structured interview. Interviews were the second phase of a randomized cross-over study using standard insulin therapy with or without CGM and remote monitoring for two 3-month periods. Open-ended questions were used to explore parents' real-life experiences of the remote monitoring and CGM system. Interviews were analysed using thematic analysis. RESULTS: Five themes related to remote monitoring emerged: (i) impact on sleep quality for the parents, (ii) peace of mind, (iii) impact on anxiety, (iv) freedom and confidence for the parents and children, and (v) impact on relationships. Furthermore, parents reported on themes related to CGM in general, such as better understanding of how to manage and control their child's diabetes and experiences related to physical or technical aspects. CONCLUSION: Overall, parents of primary school children reported that using remote monitoring and CGM was a mostly beneficial experience. However, negative aspects within the themes were also reported. These findings will help to provide a structure to discuss parent and child expectations and provide targeted education at the start of using remote monitoring and CGM.

Surface Polysaccharide Mutants Reveal that Absence of O Antigen Reduces Biofilm Formation of Actinobacillus pleuropneumoniae.

Actinobacillus pleuropneumoniae is a Gram-negative bacterium belonging to the Pasteurellaceae family and the causative agent of porcine pleuropneumonia, a highly contagious lung disease causing important economic losses. Surface polysaccharides, including lipopolysaccharides (LPS) and capsular polysaccharides (CPS), are implicated in the adhesion and virulence of A. pleuropneumoniae, but their role in biofilm formation is still unclear. In this study, we investigated the requirement for these surface polysaccharides in biofilm formation by A. pleuropneumoniae serotype 1. Well-characterized mutants were used: an O-antigen LPS mutant, a truncated core LPS mutant with an intact O antigen, a capsule mutant, and a poly-N-acetylglucosamine (PGA) mutant. We compared the amount of biofilm produced by the parental strain and the isogenic mutants using static and dynamic systems. Compared to the findings for the biofilm of the parental or other strains, the biofilm of the O antigen and the PGA mutants was dramatically reduced, and it had less cell-associated PGA. Real-time PCR analyses revealed a significant reduction in the level of pgaA, cpxR, and cpxA mRNA in the biofilm cells of the O-antigen mutant compared to that in the biofilm cells of the parental strain. Specific binding between PGA and LPS was consistently detected by surface plasmon resonance, but the lack of O antigen did not abolish these interactions. In conclusion, the absence of the O antigen reduces the ability of A. pleuropneumoniae to form a biofilm, and this is associated with the reduced expression and production of PGA.

Induction cetuximab, paclitaxel, and carboplatin followed by chemoradiation with cetuximab, paclitaxel, and carboplatin for stage III/IV head and neck squamous cancer: a phase II ECOG-ACRIN trial (E2303).

BACKGROUND: E2303 evaluated cetuximab, paclitaxel, and carboplatin used as induction therapy and concomitant with radiation therapy in patients with stage III/IV head and neck squamous cell carcinoma (HNSCC) determining pathologic complete response (CR), event-free survival (EFS), and toxicity. PATIENTS AND METHODS: Patients with resectable stage III/IV HNSCC underwent induction therapy with planned primary site restaging biopsies (at week 8 in clinical complete responders and at week 14 if disease persisted). Chemoradiation (CRT) began week 9. If week 14 biopsy was negative, patients completed CRT (68-72 Gy); otherwise, resection was carried out. p16 protein expression status was correlated with response/survival. RESULTS: Seventy-four patients were enrolled; 63 were eligible. Forty-four (70%) were free of surgery to the primary site, progression, and death 1-year post-treatment. Following induction, 41 (23 CR) underwent week 8 primary site biopsy and 24 (59%) had no tumor (pathologic CR). Week 14 biopsy during chemoradiation (50 Gy) in 34 (15 previously positive biopsy; 19 no prior biopsy) was negative in 33. Thus 90% of eligible patients completed CRT. Overall survival and EFS were 78% and 55% at 3 years, respectively. Disease progression in 23 patients (37%) was local only in 10 (16%), regional in 5 (8%), local and regional in 2 (3%), and distant in 5 patients (8%). There were no treatment-related deaths. Toxicity was primarily hematologic or radiation-related. p16 AQUA score was not associated with response/survival. CONCLUSIONS: Induction cetuximab, paclitaxel, and carboplatin followed by the same drug CRT is safe and induces high primary site response and promising survival. CLINICAL TRIALS NUMBER: NCT 00089297.

Recurrence of low back pain: A difficult outcome to predict. Development and validation of a multivariable prediction model for recurrence in patients recently recovered from an episode of non-specific low back pain.

BACKGROUND: Recurrence of low back pain (LBP) is common. If clinicians could identify an individual's risk of recurrence, this would enhance clinical decision-making and tailored patient care. OBJECTIVE/DESIGN: To develop and validate a simple tool to predict the probability of a recurrence of LBP by 3- or 12-months following recovery. METHODS: Data utilised for the prediction model development came from a prospective inception cohort study of participants (n = 250) recently recovered from LBP, who had sought care from chiropractic or physiotherapy services. The outcome measure was a recurrence of activity-limiting LBP. Candidate predictor variables (e.g., basic demographics, LBP history, levels of physical activity, etc) collected at baseline were considered for inclusion in a multivariable Cox model. The model's performance was tested in a separate validation dataset of participants (n = 261) involved in a randomised controlled trial investigating exercise for the prevention of LBP recurrences. RESULTS: The final model included the number of previous episodes, total sitting time, and level of education. In the development sample, discrimination was acceptable (Harrell's C-statistic = 0.61, 95% CI, 0.59-0.62), but in the validation sample, discrimination was poor (0.56, 95% CI, 0.54-0.58). Calibration of the model in the validation dataset was acceptable at 3 months but was less precise at 12 months. CONCLUSION: The developed prediction model, which included number of previous episodes, total sitting time, and level of education, did not perform adequately in the validation sample to recommend its use in clinical practice. Predicting recurrence of LBP in clinical practice remains challenging.

Convolutional neural networks for the automatic segmentation of lumbar paraspinal muscles in people with low back pain.

The size, shape, and composition of paraspinal muscles have been widely reported in disorders of the cervical and lumbar spine. Measures of size, shape, and composition have required time-consuming and rater-dependent manual segmentation techniques. Convolutional neural networks (CNNs) provide alternate timesaving, state-of-the-art performance measures, which could realise clinical translation. Here we trained a CNN for the automatic segmentation of lumbar paraspinal muscles and determined the impact of CNN architecture and training choices on segmentation performance. T2-weighted MRI axial images from 76 participants (46 female; age (SD): 45.6 (12.8) years) with low back pain were used to train CNN models to segment the multifidus, erector spinae, and psoas major muscles (left and right segmented separately). Using cross-validation, we compared 2D and 3D CNNs with and without data augmentation. Segmentation accuracy was compared between the models using the Sørensen-Dice index as the primary outcome measure. The effect of increasing network depth on segmentation accuracy was also investigated. Each model showed high segmentation accuracy (Sørensen-Dice index ≥ 0.885) and excellent reliability (ICC2,1 ≥ 0.941). Overall, across all muscles, 2D models performed better than 3D models (p = 0.012), and training without data augmentation outperformed training with data augmentation (p < 0.001). The 2D model trained without data augmentation demonstrated the highest average segmentation accuracy. Increasing network depth did not improve accuracy (p = 0.771). All trained CNN models demonstrated high accuracy and excellent reliability for segmenting lumbar paraspinal muscles. CNNs can be used to efficiently and accurately extract measures of paraspinal muscle health from MRI.

Characteristics and Effectiveness of Interventions That Target the Reporting, Communication, or Clinical Interpretation of Lumbar Imaging Findings: A Systematic Review.

BACKGROUND: Patients and clinicians may misinterpret the clinical importance of imaging findings in patients with low back pain, leading to potential harm related to overdiagnosis. PURPOSE: Our aims were to qualitatively summarize the characteristics of tested interventions that target the reporting, communication, or clinical interpretation of lumbar imaging findings and determine whether interventions are effective in improving low back pain-related health outcomes, health care use, or health care costs. DATA SOURCES: PubMed, MEDLINE, CINAHL, EMBASE, PsycINFO, and the Cochrane Library were searched from inception to October 20, 2021. STUDY SELECTION: The search retrieved 4394 articles, nine articles (seven studies) met the inclusion criteria to summarize intervention characteristics. Five of these studies had an adequate design for evaluating intervention effectiveness. DATA ANALYSES: Intervention characteristics were summarized using the Template for Intervention Description and Replication checklist. Effectiveness data were extracted from short, intermediate, and long-term follow-up points. Studies were assessed for risk of bias, and Grading of Recommendations Assessment, Development and Evaluation methodology was used to determine the certainty of the evidence. DATA SYNTHESIS: Four studies investigated the insertion of prevalence information into imaging reports. Single studies investigated withholding diagnostic information, education, and reassurance. Moderate-quality evidence (from 1 study) suggests that inserting prevalence information into imaging reports probably does not change the overall health care use in the long-term but may reduce opioid prescribing. LIMITATIONS: The available evidence is limited, and a meta-analysis was not possible. CONCLUSIONS: Further work is required to develop and test interventions that target the reporting, communication, and clinical interpretation of lumbar imaging findings that may reduce overdiagnosis and improve the management of low back pain.

Cardioplegic strategies to protect the hypertrophic heart during cardiac surgery.

Cardioplegic arrest and cardiopulmonary bypass are key triggers of myocardial injury during aortic valve surgery. Cardioplegic ischaemic arrest is associated with disruption to metabolic and ionic homeostasis in cardiomyocytes. These changes predispose the heart to reperfusion injury caused by elevated intracellular reactive oxygen species and calcium. Cardiopulmonary bypass is associated with an inflammatory response that can generate systemic oxidative stress which, in turn, provokes further damage to the heart. Techniques of myocardial protection are routinely applied to all hearts, irrespective of their pathology, although different cardiomypathies respond differently to ischaemia and reperfusion injury. In particular, the efficacy of cardioprotective interventions used to protect the hypertrophic heart in patients with aortic valve disease remains controversial. This review will describe key cellular changes in hypertrophy, response to ischaemia and reperfusion and cardioplegic arrest and highlight the importance of optimising cardioprotective strategies to suit hypertrophic hearts.

Increased level of arginase activity correlates with disease severity in HIV-seropositive patients.

Infection with human immunodeficiency virus (HIV) results in a chronic infection that progressively impairs the immune system. Although depletion of CD4(+) T cells is frequently used to explain immunosuppression, chronicity of infection and progressive loss of CD4(+) T cells are not sufficient to fully account for immune dysregulation. Arginase-induced l-arginine deprivation is emerging as a key mechanism for the down-regulation of immune responses. Here, we hypothesized that the level of arginase activity increases with disease severity in HIV-seropositive patients. We determined the levels of arginase activity in peripheral blood mononuclear cells from HIV-seropositive patients and uninfected control participants. Our results show that peripheral blood mononuclear cells from HIV-seropositive patients with low CD4(+) T cell counts expressed statistically significantly higher levels of arginase activity, compared with patients with high CD4(+) T cell counts or uninfected control participants. Furthermore, we found a statistically significant correlation between high level of arginase activity and high viral load in HIV-seropositive patients.

Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome.

We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia.

Do older adults with chronic low back pain differ from younger adults in regards to baseline characteristics and prognosis?

BACKGROUND: Low back pain (LBP) in older adults is poorly understood because the vast majority of the LBP research has focused on the working aged population. The aim of this study was to compare older adults consulting with chronic LBP to middle aged and young adults consulting with chronic LBP, in terms of their baseline characteristics, and pain and disability outcomes over 1 year. METHODS: Data were systematically collected as part of routine care in a secondary care spine clinic. At initial presentation patients answered a self-report questionnaire and underwent a physical examination. Patients older than 65 were classified as older adults and compared to middle aged (45-65 years old) and younger adults (17-44 years old) for 10 baseline characteristics. Pain intensity and disability were collected at 6 and 12 month follow-ups and compared between age groups. RESULTS: A total of 14,479 participants were included in the study. Of these 3087 (21%) patients were older adults, 6071 (42%) were middle aged and 5321 (37%) were young adults. At presentation older adults were statistically different to the middle aged and younger adults for most characteristics measured (e.g. less intense back pain, more leg pain and more depression); however, the differences were small. The change in pain and disability over 12 months did not differ between age groups. CONCLUSIONS: This study found small baseline differences in older people with chronic LBP compared to middle aged and younger adults. There were no associations between age groups and the clinical course. SIGNIFICANCE: Small baseline differences exist in older people with chronic low back pain compared to middle aged and younger adults referred to secondary care for chronic low back pain. Older adults present with slightly less intense low back pain but slightly more intense leg pain. Changes in pain intensity and disability over a 12 month period were similar across all age groups.

Predicting recovery in patients with acute low back pain: A Clinical Prediction Model.

BACKGROUND: There is substantial variability in the prognosis of acute low back pain (LBP). The ability to identify the probability of individual patients recovering by key time points would be valuable in making informed decisions about the amount and type of treatment to provide. Predicting recovery based on presentation 1-week after initially seeking care is clinically important and may be more accurate than predictions made at initial presentation. The aim of this study was to predict the probability of recovery at 1-week, 1-month and 3-months after 1-week review in patients who still have LBP 1-week after initially seeking care. METHODS: The study sample comprised 1070 patients with acute LBP, with a pain score of ≥2 1-week after initially seeking care. The primary outcome measure was days to recovery from pain. Ten potential prognostic factors were considered for inclusion in a multivariable Cox regression model. RESULTS: The final model included duration of current episode, number of previous episodes, depressive symptoms, intensity of pain at 1-week, and change in pain over the first week after seeking care. Depending on values of the predictor variables, the probability of recovery at 1-week, 1-month and 3-months after 1-week review ranged from 4% to 59%, 19% to 91% and 30% to 97%, respectively. The model had good discrimination (C = 0.758) and calibration. CONCLUSIONS: This study found that a model based on five easily collected variables could predict the probability of recovery at key time points in people who still have LBP 1-week after seeking care. SIGNIFICANCE: A clinical prediction model based on five easily collected variables was able to predict the likelihood of recovery from an episode of acute LBP at three key time points. The model had good discrimination (C = 0.758) and calibration.

Prospective Comparison of Changes in Lumbar Spine MRI Findings over Time between Individuals with Acute Low Back Pain and Controls: An Exploratory Study.

BACKGROUND AND PURPOSE: The clinical importance of lumbar MR imaging findings is unclear. This study was an exploratory investigation of whether lumbar spine MR imaging findings change more commonly during a 12-week period in individuals with acute low back pain compared with pain-free controls. MATERIALS AND METHODS: Twenty individuals with recent-onset low back pain and 10 pain-free controls were recruited into an exploratory prospective cohort study. All participants had a lumbar spine MR imaging at baseline and repeat MR imaging scans at 1, 2, 6, and 12 weeks. The proportion of individuals who had MR imaging findings that changed during the 12-week period was compared with the same proportion in the controls. RESULTS: In 85% of subjects, we identified a change in at least 1 MR imaging finding during the 12 weeks; however, the proportion was similar in the controls (80%). A change in disc herniation, annular fissure, and nerve root compromise was reported more than twice as commonly in the subjects as in controls (65% versus 30%, 25% versus 10%, and 15% versus 0%, respectively). Caution is required in interpreting these findings due to wide confidence intervals, including no statistical difference. For all other MR imaging findings, the proportions of subjects and controls in whom MR imaging findings were reported to change during 12 weeks were similar. CONCLUSIONS: Changes in MR imaging findings were observed in a similar proportion of the low back pain and control groups, except for herniations, annular fissures, and nerve root compromise, which were twice as common in subjects with low back pain.

Phenotypic variability in anchorage-independent growth by a human breast tumor cell line.

Possible mechanisms responsible for expression of anchorage independence were investigated with the use of the human breast carcinoma cell line Hs578T. This phenotype was not stable and most likely occurred via alterations in gene expression, causing secretion of growth factor (s). Colony-forming efficiency in methylcellulose was proportional to initial plating density at low passage number and increased with passage in culture. At high passages, there was less sensitivity to initial plating density, suggesting less dependence on surrounding cells for feeding effects. Clonal variants isolated in methylcellulose maintained a higher plating efficiency when kept in suspension, and removal of selective pressure resulted in the loss of the high level of expression upon subsequent challenge in suspension. In contrast to other systems, anchorage-dependent clones acquired the ability to grow in methylcellulose after only one passage in culture. This suggests that rapid variation at rates not typical of classical somatic mutation plays a role in expression of anchorage independence. Exposure to 5-azacytidine, which decreases methylation of DNA and may thereby activate gene transcription, increased the incidence of anchorage-independent growth 20 times; whereas treatment with 6-azacytidine had no effect. Unconcentrated medium conditioned by cells previously exposed to 5-azacytidine or by cells at high passage stimulated growth in suspension by as much as 10.9 times. The factor(s) present in this conditioned medium was stable to heat up to 63 degrees C for 30 minutes and was larger than 12,000-14,000 mol wt as determined by dialysis.

Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus.

BACKGROUND: Patients with acute lymphoblastic leukemia are often treated with 6-mercaptopurine, and those with homozygous deficiency in thiopurine S-methyltransferase (TPMT) enzyme activity have an extreme sensitivity to this drug as a result of the accumulation of higher cellular concentrations of thioguanine nucleotides. We studied the metabolism, dose requirements, and tolerance of 6-mercaptopurine among patients with different TPMT phenotypes. METHODS: We compared, by use of statistical modeling, 6-mercaptopurine pharmacology and tolerance in 180 patients who achieved remission on St. Jude Children's Research Hospital Protocol Total XII composed of weekly methotrexate (40 mg/m(2)) and daily oral 6-mercaptopurine (75 mg/m(2)) given for 2.5 years, interrupted every 6 weeks during the first year for treatment with either high-dose methotrexate or teniposide plus cytarabine. Statistical tests were two-sided. RESULTS: Erythrocyte concentrations of thioguanine nucleotides (pmol/8 x 10(8) erythrocytes) were inversely related to TPMT enzyme activity (P<.01), with averages (+/- standard deviations) of 417 (+/-179), 963 (+/-752), and 3565 (+/-1282) in TPMT homozygous wild-type (n = 161), heterozygous (n = 17), and homozygous-deficient (n = 2) patients, respectively. There was complete concordance between TPMT genotype and phenotype in a subset of 28 patients for whom TPMT genotype was determined. There were no sex differences in thioguanine nucleotide concentrations (P =.24), TPMT enzyme activity (P =.22), or average weekly prescribed dose of 6-mercaptopurine (P=.49). The cumulative incidence of 6-mercaptopurine dose reductions due to toxicity was highest among patients homozygous for mutant TPMT (100%), intermediate among heterozygous patients (35%), and lowest among wild-type patients (7%) (P<.001), with average (+/- standard deviation) final weekly 6-mercaptopurine doses of 72 (+/-60), 449 (+/-160), and 528 (+/-90) mg/m(2), respectively. Lowering doses of 6-mercaptopurine in TPMT heterozygotes and in deficient patients allowed administration of full protocol doses of other chemotherapy while maintaining high thioguanine nucleotide concentrations. CONCLUSION: We conclude that genetic polymorphism in TPMT is an important determinant of mercaptopurine toxicity, even among patients who are heterozygous for this trait.

Immortalization in culture: occurrence at a late stage in the progression of breast cancer.

The properties in culture of 3 breast cancer effusion metastases, obtained over approximately 2 years from the same patient, were examined. Despite repeated attempts with cryopreserved cells, only the last specimen reproducibly exhibited immortality in culture; the first 2 specimens grew initially but failed to develop into cell lines. Each specimen was unique in morphology and growth properties, although karyotypic markers indicated a common origin. Aberrations of chromosomes 1 and 11 marked these near-diploid cells, and further structural alterations of chromosome 11 accompanied the transition of biological properties observed in the third specimen.

A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines.

A monoclonal antibody (TAb 250) specific to an extracellular epitope of the c-erbB-2 protein (gp185) inhibited the in vitro proliferation of human breast tumor cell lines that overexpress c-erbB-2 in a dose-dependent manner. Treatment of cells with combinations of cis-diammedichloroplatinum (CDDP) and TAb 250 resulted in a significantly enhanced cytotoxic effect. This synergistic cytotoxicity was apparent over a wide range of antibody concentrations (200 pg/ml-100 micrograms/ml) including concentrations that showed no inhibitory effect alone. TAb 250 did not increase the cytotoxic effect of CDDP in a cell line exhibiting no detectable level of gp185. Athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of gp185 showed a greatly enhanced inhibition of tumor growth when treated with TAb 250 and CDDP compared to treatment with the antibody or CDDP alone. This effect was specific inasmuch as TAb 250 did not enhance the growth-inhibitory effect of CDDP on tumor xenografts which were not expressing gp185.

Understanding patient beliefs regarding the use of imaging in the management of low back pain.

BACKGROUND: Imaging for low back pain (LBP) remains common despite guidelines recommending against routine imaging. Patient beliefs about imaging may contribute to the problem. This study aimed to quantitatively investigate patient beliefs regarding the need for imaging in managing LBP and to investigate whether personal characteristics, pain characteristics or back pain beliefs are associated with imaging beliefs. METHODS: A survey was performed of consecutive patients presenting to general medical practitioners in Sydney, Australia. Nine medical clinics were selected across varied socioeconomic regions. Survey questions assessed beliefs about the importance of imaging for LBP, collected demographic information, LBP history and general beliefs about back pain. Descriptive statistics and multivariate logistic regression were used to analyse findings. RESULTS: Three hundred completed surveys were collected with a 79.6% response rate. The mean age was 44 years and 60.7% of respondents were women. Exactly, 54.3% (95% CI: 48.7-58.9%) believed that imaging was necessary for the best medical care for LBP. Exactly, 48.0% (95% CI: 42.4-53.6%) believed that everyone with LBP should obtain imaging. Increased age, lower education level, non-European or non-Anglo-saxon cultural background, history of previous imaging and Back Beliefs Questionnaire scores were associated with beliefs that imaging was necessary. CONCLUSION: Approximately, half of all patients presenting to a medical doctor consider low back imaging to be necessary. This may have important implications for overutilization of low back imaging investigations. Knowledge of the factors associated with the patient's belief that imaging is necessary may be helpful in designing appropriate interventions to reduce unnecessary imaging for LBP.

Effect of hydration on methotrexate plasma concentrations in children with acute lymphocytic leukemia.

Hydration and urinary alkalinization are used with high-dose methotrexate (HDMTX) to minimize renal toxicity resulting from methotrexate (MTX) precipitation in the kidney tubules. The effect of two hydration and alkalinization schedules on MTX plasma concentrations were evaluated in 100 children with acute lymphocytic leukemia (ALL) following two courses of MTX, 2 g/m2. The mean 21- and 44-hour MTX plasma concentrations were significantly lower in the group receiving the greater hydration and alkalinization schedule: 0.79 (0.90 SD) v 1.39 (1.99 SD) mumol/L for 21-hour MTX plasma concentrations, P = .01; and 0.18 (0.38 SD) v 0.25 (0.50 SD) mumol/L for 44-hour MTX plasma concentrations, P = .01. Although the overall incidence of toxic events was similar in both groups, the incidence of severe toxicity was reduced in the group that received the greater hydration and alkalinization, 6% v 16%. This study demonstrated that the amount of hydration and alkalinization can affect MTX plasma concentrations. Optimizing the hydration and alkalinization schedule is important for minimizing the incidence of severe toxicity associated with HDMTX.

Therapy for localized Ewing's sarcoma of bone.

Fifty-two previously untreated patients with localized Ewing's sarcoma of bone were treated with nonintensive chemotherapy in combination with surgery or radiation therapy (RT). RT was delivered to limited volumes in a dose dependent on the initial response to induction chemotherapy (30 to 35 Gy v 50 to 55 Gy). Fifty of the 52 patients achieved complete or partial responses with induction chemotherapy, with one nonresponding patient rendered free of tumor with surgery. Fifty patients were evaluable for local control of tumor and overall response to protocol therapy. Seventeen relapses have occurred; three metastatic, four local plus metastatic, and ten local. Two factors predicted worse disease-free survival: high WBC count (P = .03) and size of primary tumor (P = .05). Of the 14 local recurrences, 12 occurred in 28 patients who presented with primary tumors greater than 8 cm in size while only two of 22 patients with lesions less than 8 cm had local recurrence. The Kaplan-Meier estimate of disease-free survival at 3 years is 82% for those with small lesions and 64% for those with larger lesions. Site of primary was of no prognostic value (P = .27). The 5-year survival estimate for all patients is 80% (median time on study, 3.3 years).

A prospective study of Hickman/Broviac catheters and implantable ports in pediatric oncology patients.

We prospectively studied the continuous function and complication rates of 286 central venous catheters consecutively placed in 264 children and young adults at a single institution over a 19-month period (median follow-up, 376 days). Externalized catheters (91 Hickman [H], 113 Broviac [B]) and implantable ports (n = 82) were compared for complications, including infection and thrombosis. The most frequent major complication of all catheters was infection, although the rates of infection varied with the duration of catheter use and were generally lower than reported by others. Overall, when catheter failures (removal) for infection, obstruction, or dislodgement were considered, ports had a significantly longer failure-free duration of use (P = .0024) than did externalized catheters. Likewise, ports had a significantly longer infection-free (P less than .01) duration of use than H and B catheters. However, differences in patient age and clinical characteristics among the three catheter groups may have affected the outcome. In analysis of pairs matched for diagnosis, therapy, and age, ports had lower infection rates than did B catheters after 100 days (P = .053). This difference became significant at 400 days of catheter use (P = .029). Although there was a trend toward lower rates of infections for ports v H catheters, this difference was not significant. In view of our results in matched pairs, selection of catheter type based on clinical characteristics and patient preferences remains a reasonable therapeutic approach despite the apparent advantages of ports. The superiority of ports for long-term use (greater than 100 days) needs to be confirmed in a large randomized clinical trial.