Publications

BACKGROUND

Metabolic bone disease and bariatric surgery have long been interconnected. The objective of this study is to better understand the mechanisms of bone mass loss after Roux-en-Y gastric bypass (RYGB) surgery. We evaluated mineral homeostasis and bone mass in diet-induced obese (DIO) rats after RYGB or sham surgery.

METHODS

Twelve DIO male Sprague Dawley rats underwent RYGB (n = 8) or sham (n = 4) surgery at 21 weeks of age. Postoperatively, animals ate an ad libitum 40% fat, normal calcium diet and were euthanized 22 weeks later. Serum and urine chemistries, insulin, leptin, bone turnover markers (BTM), and calciotropic and gut hormones were measured before and 22 weeks after surgery. Femurs were analyzed using microcomputed tomography (µCT).

RESULTS

Compared to sham, RYGB animals had lower serum bicarbonate, calcium, 25-hydroxyvitamin D, insulin, and leptin levels with higher serum parathyroid hormone, peptide YY, and urinary calcium at 43 weeks of age. Sham control rats gained weight and had coupled decreases in formation (P1NP and OC) and unchanged resorption (CTX) BTMs. Comparatively, RYGB animals had higher serum CTX and OC but even lower P1NP levels than controls. µCT revealed lower trabecular bone volume, number, and thickness and lower cortical bone volume, thickness, and moment of inertia relative to controls.

CONCLUSION

In rats with DIO, long-term RYGB-associated bone resorption appears to be driven in part by vitamin D malabsorption and secondary hyperparathyroidism. Other mechanisms, such as chronic acidosis, changes in fat-secreted hormones, and persistently elevated gut-derived hormone peptide YY, may also contribute to observed bone mass differences. Further investigation of these potential contributors to bone loss may lead to new targets for skeletal maintenance after RYGB.

OBJECTIVE

Diabetes and hypertension, common conditions in antiretroviral-treated HIV-infected individuals, are associated with glomerular hyperfiltration, which precedes the onset of proteinuria and accelerated kidney function decline. In the Multicenter AIDS Cohort Study, we examined the extent to which hyperfiltration is present and associated with metabolic, cardiovascular, HIV and treatment risk factors among HIV-infected men.

DESIGN

Cross-sectional cohort using direct measurement of glomerular filtration rate by iohexol plasma clearance for 367 HIV-infected men and 241 HIV-uninfected men who were free of chronic kidney disease.

METHODS

Hyperfiltration was defined as glomerular filtration rate above 140-1 ml/min per 1.73 m per year over age 40. Multivariate logistic regression was used to estimate the odds ratios (ORs) of prevalent hyperfiltration for metabolic, cardiovascular, HIV and cumulative antiretroviral exposure factors.

RESULTS

Among individuals without chronic kidney disease, the prevalence of hyperfiltration was higher for HIV-infected participants (25%) compared to uninfected participants (17%; P = 0.01). After adjustment, HIV infection remained associated with hyperfiltration [OR 1.70, 95% confidence interval (CI) 1.11-2.61] and modified the association between diabetes and hyperfiltration, such that the association among HIV-uninfected men (OR 2.56, 95% CI 1.33-5.54) was not observed among HIV-infected men (OR 1.19, 95% CI 0.69-2.05). These associations were independent of known risk factors for hyperfiltration. Indicators of hyperglycemia and hypertension were also associated with hyperfiltration as was cumulative zidovudine exposure.

CONCLUSION

Hyperfiltration, a potential modifiable predictor of kidney disease progression, is significantly higher among antiretroviral-treated HIV-infected men. Furthermore, HIV-infection nullifies the association of diabetes and hyperfiltration present in HIV-uninfected men.

Magnetic resonance (MR) imaging characteristics are commonly used to help predict intracranial disease categories in dogs, however, few large studies have objectively evaluated these characteristics. The purpose of this retrospective study was to evaluate MR characteristics that have been used to differentiate neoplastic, inflammatory, and vascular intracranial diseases in a large, multi-institutional population of dogs. Medical records from three veterinary teaching hospitals were searched over a 6-year period for dogs that had diagnostic quality brain MR scans and histologically confirmed intracranial disease. Three examiners who were unaware of histologic diagnosis independently evaluated 19 MR lesion characteristics totaling 57 possible responses. A total of 75 dogs with histologically confirmed intracranial disease were included in analyses: 51 with neoplasia, 18 with inflammatory disease, and six with cerebrovascular disease. Only strong contrast enhancement was more common in neoplasia than other disease categories. A multivariable statistical model suggested that extra-axial origin, T2-FLAIR mixed intensity, and defined lesion margins were also predictive of neoplasia. Meningeal enhancement, irregular lesion shape, and multifocal location distinguished inflammatory diseases from the other disease categories. No MR characteristics distinguished vascular lesions and these appeared most similar to neoplasia. These results differed from a previous report describing seven MR characteristics that were predictive of neoplasia in dogs and cats. Findings from the current study indicated that the high performance of MR for diagnosing canine intracranial diseases might be due to evaluator recognition of combinations of MR characteristics vs. relying on any one MR characteristic alone.

We compared different techniques for measuring gut HIV reservoirs and assessed for HIV in non-CD4 T cells. HIV DNA levels were similar when measured from rectal biopsies and isolated rectal cells, while HIV RNA tended to be higher in rectal cells. HIV DNA levels in total rectal cells were greater than those predicted from levels in sorted CD4 T cells, suggesting a reservoir in non-CD4 T cells, and HIV DNA was detected in sorted myeloid cells (7/7 subjects).

BACKGROUND

Kaposi sarcoma (KS) remains the second most frequently diagnosed HIV-related malignancy (HRM) worldwide and most common HRM in sub-Saharan Africa where HIV is most prevalent and human herpesvirus 8 (HHV-8), the precipitating agent for the development of KS, is endemic. The majority of KS patients would likely benefit from systemic chemotherapy in addition to the initiation of antiretroviral therapy (ART). However, as paediatric staging and treatment criteria are not readily available, there are no uniform treatment criteria.

OBJECTIVES

To describe the efficacy and effectiveness of current treatment options for HIV-associated KS in ART-treated paediatric populations.

SEARCH METHODS

We used standard Cochrane methods to search electronic databases and conference proceedings with relevant search terms without limits to language.

SELECTION CRITERIA

Randomised controlled trials, cohort studies, and case-control studies of HIV-infected infants and children <18 years old treated with ART and diagnosed with KS.

DATA COLLECTION AND ANALYSIS

Abstracts of all studies identified by electronic or bibliographic scanning were examined independently by two authors. We initially identified 920 references and examined 15 in detail for study eligibility. Data were abstracted independently using a standardised abstraction form.

MAIN RESULTS

After initially screening 920 titles, 15 full-text articles were closely examined by two authors. We identified four cohort studies that met our inclusion criteria for data extraction, coding, and potential meta-analysis.Using the Newcastle-Ottawa Scale and Cochrane risk of bias assessments, all observational studies had cohorts that were representative of average (treated and untreated) HIV-infected children with Kaposi sarcoma. For all outcomes of interest, no study adjusted for any other potential confounders. Two of four observational studies either explicitly described complete follow up of the study participants and/or described the characteristics of the participants lost to follow up.The use of ART together with a chemotherapeutic regimen versus ART alone appears to increase the likelihood of KS remission in HIV-infected children diagnosed with KS, although data are sparse and not adequately adjusted for staging of disease and comorbidities. Additionally, though data are sparse, the use of ART together with a chemotherapeutic regimen versus chemotherapy alone in some analyses appears to increase the likelihood of KS remission and reduce the risk of death in HIV-infected children diagnosed with KS.In this analysis, we found that the quality of evidence was very low due to small sample sizes and a paucity of paediatric literature.

AUTHORS' CONCLUSIONS

Data describing the efficacy of different treatment options for pediatric KS, to include chemotherapy and ART, are sparse. However, the use of ART together with a chemotherapy regimen may be superior to the use of ART alone or of chemotherapy alone.