Rapid Reduction in Use of Antidiabetic Medication after Laparoscopic Sleeve Gastrectomy: The Newfoundland and Labrador Bariatric Surgery Cohort (BaSCo) Study

Background:

Patients who have undergone bariatric surgery generally need fewer medications as they experience improvement in, or even resolution of, various medical conditions, including type 2 diabetes mellitus, hypertension, and dyslipidemia. Published data on changes in medication use after laparoscopic sleeve gastrectomy, a type of bariatric surgery that is growing in popularity, are limited.

Objective:

To determine whether patients took fewer medications for management of type 2 diabetes, hypertension, and dyslipidemia after laparoscopic sleeve gastrectomy, relative to preprocedure medications.

Methods:

In this prospective, single-centre cohort study, a nurse practitioner used standard medication reconciliation and study data-extraction forms to interview adult patients who had undergone laparoscopic sleeve gastrectomy and determine their medication use and pertinent demographic data. The data were analyzed using generalized estimating equations and standard statistical software. Outcome measures included changes in the use of antidiabetic, antihypertensive, and antilipemic medications at 1, 3, and 6 months after the surgery.

Results:

A total of 65 patients who underwent laparoscopic sleeve gastrectomy between May 2011 and January 2014 met the study inclusion criteria. Before surgery, the 30 patients with type 2 diabetes were taking an average of 1.9 antidiabetic medications. One month after the procedure, 15 (50%) had discontinued all antidiabetic medications, with a further decline at 3 and 6 months (p < 0.001 at each time point). Among the patients who were taking antihypertensives (n = 48) and antilipemics (n = 33) before surgery, the decline in use occurred at a more modest rate, with 6 (12%) and 2 (6%), respectively, discontinuing these medication classes within 1 month, and 12 (25%) (p = 0.001) and 8 (24%) (p = 0.015) having discontinued by 6 months.

Conclusions:

These findings suggest that patients with a history of type 2 diabetes mellitus, hypertension, and/or dyslipidemia who undergo laparoscopic sleeve gastrectomy are less likely to require disease-specific medications shortly after surgery.     

Development of toxicity values and exposure estimates for tetrabromobisphenol A: application in a margin of exposure assessment

Tetrabromobisphenol A (TBBPA) is used in a diverse array of products to improve fire safety. The National Toxicology Program (NTP) recently completed a 2‐year bioassay for TBBPA. The objective of the present study was to develop a cancer‐based and a non‐cancer based toxicity value and to compare such to appropriate estimates of human exposure. Data from the NTP 2‐year and 13‐week studies were selected to develop candidate toxicity values. Benchmark dose modeling and subsequent evaluation of candidate values resulted in selection of an oral reference dose (RfD) of 0.6 mg kg^?1 day^?1 based on uterine hyperplasia in rats and an oral cancer slope factor (OSF) of 0.00315 per mg kg^?1 day^?1 based on an increased incidence of uterine tumors in rats. Lifetime average daily dose (LADD) estimates ranged from 2.2 E^?7 to 3.9 E^?6 mg kg^?1 day^?1 based on age‐adjusted exposures to TBBPA via breast milk consumption, dietary intake, soil/dust ingestion and drinking water ingestion in infants, young children, older children and adults. Average daily dose (ADD) estimates ranged from 3.2 E ^?7 to 8.4 E^?5 mg kg^?1 day^?1. Resulting margin of exposure (MOE) values were > 800 000 for non‐cancer endpoints and > 32 000 000 for cancer‐based endpoints. These data collectively indicate a low level of health concern associated with exposures to TBBPA based on current data. It is anticipated that the exposure estimates, along with the toxicity values described within, should be informative for understanding human health hazards associated with TBBPA. Copyright © 2015. The Authors. Journal of Applied Toxicology Published by John Wiley & Sons Ltd.     

West Nile Virus Infection Incidence Based on Donated Blood Samples and Neuroinvasive Disease Reports,Northern Texas,USA, 2012

During the 2012 outbreak of West Nile virus in the United States, approximately one third of the cases were in Texas. Of those, about half occurred in northern Texas. Models based on infected blood donors and persons with neuroinvasive disease showed, respectively, that ≈0.72% and 1.98% of persons in northern Texas became infected.     

Amphotropic or Gibbon Ape Leukemia Virus Retrovirus Binding and Transduction Correlates with the Level of Receptor mRNA in Human Hematopoietic Cell Lines

ABSTRACT: The low level of amphotropic retrovirus mediated gene transfer into human hematopoietic stem cells (HSC) has been an impediment to gene therapy for hematopoietic diseases (1). We have previously shown that mouse and human HSC have low levels of the mRNA encoding PiT-2, the amphotropic retrovirus receptor. We hypothesized that the low level of PiT-2 mRNA was responsible for the low frequency of transduction of HSC by amphotropic retroviral vectors (2). In this study we compared the level of PiT-2 and PiT-1, the Gibbon Ape Leukemia Virus receptor (GaLV), in 5 human tissue culture cell lines. PiT-2 and PiT-1 mRNA levels were highest in K562 cells and lowest in HL60 cells. In hematopoietic cell lines, the level of PiT-2 or PiT-1 mRNA correlated directly with retrovirus binding and transduction with the appropriate (amphotropic or GaLV) retrovirus vector. The level of expression of PiT-2 and PiT-1 mRNA could be increased by treatment of HL60 cells with either PMA or Interleukin-1α. The increase in the level of PiT-2 and PiT-1 mRNA correlated with increased transduction with both amphotropic and GaLV retroviral vectors. We conclude that the improved transduction was a direct effect of the increased levels of receptor mRNA and unrelated to changes in the cell cycle status.     

Cognitive function and its relationship with brain structure in myotonic dystrophy type 1

Studies have shown relationships between white matter abnormalities and cognitive dysfunction in myotonic dystrophy type 1 (DM1), but comprehensive analysis of potential structure–function relationships are lacking. Fifty adult‐onset DM1 individuals (33 female) and 68 unaffected adults (45 female) completed the Wechsler Adult Intelligence Scale‐IV (WAIS‐IV) to determine the levels and patterns of intellectual functioning. Neuroimages were acquired with a 3T scanner and were processed with BrainsTools. Regional brain volumes (regions of interest, ROIs) were adjusted for inter‐scanner variation and intracranial volume. Linear regression models were conducted to assess if group by ROI interaction terms significantly predicted WAIS‐IV composite scores. Models were adjusted for age and sex. The DM1 group had lower Perceptual Reasoning Index (PRI), Working Memory Index (WMI), and Processing Speed Index (PSI) scores than the unaffected group (PRI t₍₁₁₃₎ = ?3.28, p = 0.0014; WMI t₍₁₁₄₎ = ?3.49, p = 0.0007; PSI t₍₁₁₄₎ = ?2.98, p = 0.0035). The group by hippocampus interaction term was significant for both PRI and PSI (PRI (t₍₁₁₁₎ = ?2.82, p = 0.0057; PSI (t₍₁₁₂₎ = ?2.87, p = 0.0049)). There was an inverse association between hippocampal volume and both PRI and PSI in the DM1 group (the higher the volume, the lower the intelligence quotient scores), but no such association was observed in the unaffected group. Enlarged hippocampal volume may underlie some aspects of cognitive dysfunction in adult‐onset DM1, suggesting that increased volume of the hippocampus may be pathological.     

Aggressive spinal haemangiomas: imaging correlates to clinical presentation with analysis of treatment algorithm and clinical outcomes

Objective:

Aggressive spinal haemangiomas (those with significant osseous expansion/extraosseous extension) represent approximately 1% of spinal haemangiomas and are usually symptomatic. In this study, we correlate imaging findings with presenting symptomatology, review treatment strategies and their outcomes and propose a treatment algorithm.

Methods:

16 patients with aggressive haemangiomas were retrospectively identified from 1995 to 2013. Imaging was assessed for size, location, CT/MR characteristics, osseous expansion and extraosseous extension. Presenting symptoms, management and outcomes were reviewed.

Results:

Median patient age was 52 years. Median size was 4.5 cm. Lumbar spine was the commonest location (n = 8), followed by thoracic spine (n = 7) and sacrum (n = 2); one case involved the lumbosacral junction. 12 haemangiomas had osseous expansion; 13 had extraosseous extension [epidural (n = 11), pre-vertebral/paravertebral (n = 10) and foraminal (n = 6)]. On CT, 11 had accentuated trabeculae and 5 showed lysis. On MRI, eight were T1 hyperintense, six were T1 hypointense and all were T2 hyperintense. 11 symptomatic patients underwent treatment: chemical ablation (n = 6), angioembolization (n = 3, 2 had subsequent surgery), radiotherapy (n = 2, 1 primary and 1 adjuvant) and surgery (n = 4). Median follow-up was 20 months. Four of six patients managed only by percutaneous methods had symptom resolution. Three of four patients requiring surgery had symptom resolution.

Conclusion:

Aggressive haemangiomas cause significant morbidity. Treatment is multidisciplinary, with surgery reserved for large lesions and those with focal neurological signs. Minimally invasive procedures may be successful in smaller lesions.

Advances in knowledge:

Aggressive haemangiomas are rare, but knowledge of their imaging features and treatment strategies enhances the radiologist''s role in their management.     

Re-evaluation of serum alanine aminotransferase upper normal limit and its modulating factors in a large-scale population study.

BACKGROUND: The upper normal limit (ULN) of serum alanine-aminotrasferase (ALT) normal range was recently challenged, because patients diagnosed with liver diseases may have 'normal' or near-'normal' ALT levels, and because possible modulators are often ignored in determining normal range. AIM: To estimate the ULN for serum ALT and to identify factors modulating it. SUBJECTS AND METHODS: We reviewed medical records of subjects aged 15-90, who underwent standard panels of laboratory tests, including serum ALT, over 6 months at a central laboratory. Three groups were defined: Group 1, comprised total study population (N=272 273). Group 2 (N=87 020) comprised total study population, excluding those receiving potentially hepatotoxic drugs, or diagnosed with liver disease, or had any abnormal laboratory test results other than for triglycerides, cholesterol, glucose, or HbA1c. Group 3 (N=17 496) the 'healthy' population, from whose ALT values we established the new ULN, comprised Group 2 subjects with normal triglycerides, cholesterol, glucose, and HbA1c levels. RESULTS: The 95th percentile ALT values, corresponding to the ULN, in groups 1, 2, and 3 were 50.1, 40, and 37.5 U/l, respectively. 6.2% (16 943/273 273) of subjects whose ALT was below ULN listed by the test manufacturer (52 U/l), had ALT level above our new ULN. Linear and logistic-regression analyses showed that ALT levels were significantly modified by gender, age, glucose, cholesterol, triglycerides, and overweight/obesity diagnosis. Significant interaction was found between gender, glucose and cholesterol levels. CONCLUSIONS: In this first large-scale study of 'healthy' population, serum ALT ULN was far lower than currently accepted value. Age and gender may be considered when determining the ULN for ALT.