The microbiome in pediatric oncology

The human microbiome comprises a diverse set of microorganisms, which play a mostly cooperative role in processes such as metabolism and host defense. Next-generation genomic sequencing of bacterial nucleic acids now can contribute a much broader understanding of the diverse organisms composing the microbiome. Emerging evidence has suggested several roles of the microbiome in pediatric hematology/oncology, including susceptibility to infectious diseases, immune response to neoplasia, and contributions to the tumor microenvironment as well as changes to the microbiome from chemotherapy and antibiotics with unclear consequences. In this review, the authors have examined the evidence of the role of the microbiome in pediatric hematology/oncology, discussed how the microbiome may be modulated, and suggested key questions in need of further exploration.     

Insurance-mandated preoperative dietary counseling does not improve outcome and increases dropout rates in patients considering gastric bypass surgery for morbid obesity

BACKGROUND: Preoperative dietary counseling (PDC) before bariatric surgery is mandated by a growing number of insurance payers. Their claim is that PDC improves outcomes and postoperative compliance. We compared outcomes of GBP patients undergoing a mandatory 13 weeks of PDC (n = 72) to a contemporaneous group of patients with no such requirement (no-PDC; n = 252) who underwent operation between January 2000 and December 2002. METHODS: The PDC and no-PDC groups were characterized by similar male:female ratios (1:4 vs 1:4.6), mean age (42 years), mean body weight (324 lb vs 309 lb), and mean body mass index (BMI) (52 kg/m2 vs 50 kg/m2). The PDC group had a higher incidence of obstructive sleep apnea compared with the no-PDC group (41% vs 28%; P < .04) but otherwise the two groups had similar incidences of obesity-related comorbidities. The presurgery dropout rate was 50% higher in the PDC group than in the no-PDC group (28% vs 19%; P < .05). RESULTS: At 1 year follow-up, the no-PDC patients had a statistically greater percentage excess weight loss (67% vs 60%; P < .0001), lower BMI (32 vs 35; P < .015), and lower body weight (197 vs 218; P < .01). Resolution of major comorbidities, complication rates, 30-day postoperative mortality, and postoperative compliance with follow-up were similar in the two groups. CONCLUSIONS: The data demonstrate that insurance-mandated PDC is an obstacle to patient access for surgical treatment of severe obesity and has no impact on weight loss outcome or postsurgical compliance. PDC should be abandoned by the insurance industry.     

Factors associated with the quality of laboratory performance in the United Kingdom external quality assessment scheme for serum growth hormone

A search was made for associations between poor performance in the UK External Quality Assessment Scheme (EQAS) for serum growth hormone (GH), and a range of factors including assay method, laboratory workload and staffing, and Internal Quality Control (IQC) procedures. On the basis of the factors identified as being associated with poor performance we recommend the following. 1. Laboratories using RIA for GH should routinely analyse samples at two dilutions and report a mean result. 2. The use of 125I-GH which is 5 or more weeks old should be avoided. Tracer should also be chromatographed to remove aggregate before use. 3. Laboratories using RIA should avoid using a standard curve which covers too wide a range concentration; a curve midpoint (ie GH concentration to reduce the zero standard binding by 50%) of about 8 mU/l or less is probably acceptable. 4. It should be noted that high workloads present a risk of some loss in quality of responsible for checking IQC data. 6. Laboratories which do not have the resources to maintain fully their own RIA as outlined above should carefully consider use of an unbiased, precise IRMA. The UK EQAS has identified two assays (Boots-Celltech Sucrosep, NETRIA) that appear to meet these criteria [2]. The above observations may also be relevant to immunoassays for other peptide hormones.     

Effect of testosterone on the testicular atrophy caused by di(2-ethylhexyl)phthalate (DEHP)

The involvement of testosterone in di(2-ethylhexyl)phthalate (DEHP) induced testicular injury has been examined by coadministration of testosterone (1 mg/kg) along with DEHP (2000 mg/kg) daily for 15 days. The coadministration of testosterone and DEHP appears to have prevented the testicular injury as judged by the biochemical and histopathological changes. The sperm count and the activity of the testicular enzymes, gamma-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), sorbitol dehydrogenase (SDH), beta-glucuronidase and acid phosphatase, related with the maturation of sperm, which were significantly altered by DEHP treatment were found to be within normal levels after the combination treatment of DEHP and testosterone. The histopathological studies also showed more or less normal spermatogenic events. The results of this study have suggested the involvement of testosterone in DEHP induced testicular atrophy.     

Genetic variation in serotonin transporter alters resting brain function in healthy individuals.

BACKGROUND: Perfusion functional magnetic resonance imaging (fMRI) was used to investigate the effect of genetic variation of the human serotonin transporter (5-HTT) gene (5-HTTLPR, SLC6A4) on resting brain function of healthy individuals. METHODS: Twenty-six healthy subjects, half homozygous for the 5-HTTLPR short allele (s/s group) and half homozygous for the long allele (l/l group), underwent perfusion functional and structural magnetic resonance imaging during a resting state. The two genotype groups had no psychiatric illness and were similar in age, gender, and personality scores. RESULTS: Compared with the l/l group, the s/s group showed significantly increased resting cerebral blood flow (CBF) in the amygdala and decreased CBF in the ventromedial prefrontal cortex. The effect of functional modulation in these regions by 5-HTTLPR genotype cannot be accounted for by variations in brain anatomy, personality, or self-reported mood. CONCLUSIONS: The 5-HTTLPR genotype alters resting brain function in emotion-related regions in healthy individuals, including the amygdala and ventromedial prefrontal cortex. Such alterations suggest a broad role of the 5-HTT gene in brain function that may be associated with the genetic susceptibility for mood disorders such as depression.     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

Renal transplantation performed across a positive crossmatch: A single centre experience

The importance of certain positive crossmatches (CM⁺) in kidney transplantation remains controversial. Fifty consecutive kidney transplants were performed across a CM⁺ between Jan. 1990 – April 1994. In 19 cases there was an isolated B-cell CM⁺ (Group I), in 24 an historic T-cell IgM CM⁺ (Group II) and in 7 an historic T-cell IgG CM⁺ (Group III). Comparing groups I:II:III: early acute rejection affected 32%, 42%, 57% of grafts; mean serum creatinine at 3 months was 166, 150, 229 umol/l (p<0.05); 1 yr graft survival was 95 per cent, 96 per cent, 71 per cent (p=0.09). In group III both graft losses were in the setting of an additional current B-cell CM⁺. Conclusions: Transplantation performed in either the presence of an isolated B-cell CM⁺ or in the presence of an historic T-cell IgM CM⁺ was associated with acceptable outcomes at 1 yr. An historic T-cell IgG CM⁺ was confirmed as a contraindication to transplantation in most circumstances, especially when coupled with a current B-cell CM⁺.     

Preventing relapse in the treatment of nicotine addiction: current issues and future directions

Although smoking-cessation rates have continued to increase, the vast majority of smokers who quit eventually relapse. Between 1974 and 1985, over 1.3 million smokers quit during each of those years. However, 75% to 80% of those individuals resumed smoking within six months. This article describes the dynamic phenomenon of smoking relapse within the context of cyclical episodes of smoking and quitting during an individual's lifetime. Theories of the determinants of smoking relapse are reviewed and methods designed to prevent relapse are described. Smoking relapse is discussed in terms of three aspects of tobacco addiction: (1) biological-addiction mechanisms, (2) conditioning processes, and (3) cognitive-social learning factors. The major determinants of smoking relapse are reviewed, including nicotine withdrawal, stress, weight gain, social influences, conditioning factors, causal attributions, and environmental variables. A trans-theoretical-developmental model is explored in the longitudinal investigation of the natural history of slips (lapses) and relapse episodes. Relapse prevention interventions are described that emphasize self-awareness, self-regulation, self-efficacy, affect regulation, social support, and lifestyle balance. Recent developments in pharmacological adjuncts to treatment are also examined. It is concluded that innovative relapse prevention methods need to be designed for hard-core smokers with histories of cessation failures, substance abuse and/or psychiatric impairment. These and other recommendations for future research on smoking relapse and relapse prevention are discussed.