A pilot study to identify pre- and peri-operative risk factors for airway complications following adenotonsillectomy for treatment of severe pediatric OSA

Objective

A pilot study to identify risk factors predicting post-operative complications in children with severe OSA undergoing adenotonsillectomy.

Methods

Retrospective review in a tertiary care academic institution. Two-stage least squares regression analysis and instrumental variable analysis to allow for modeling of pre- and peri-operative risk factors as having significance in predicting post-operative morbidity.

Results

Eighty-three children (mean age 4.88 ± 3.09 years) with apnea-hypopnea index (AHI) ≥10 who were observed overnight following adenotonsillectomy were evaluated for rates of major (increased level of care, CPAP/BiPAP use, pulmonary edema and reintubation) and minor (oxygen saturation <90%) airway complications as well as total observation costs. Major and minor complications occurred in 4.8% and 19.3% of children, respectively. Age <2 years (p < 0.01), AHI >24 (p < 0.05), intra-operative laryngospasm requiring treatment (p < 0.05), oxygen saturations <90% on room air in PACU (p < 0.05) and PACU stay >100 min (p < 0.01) independently predicted post-operative complications. Children with any one of these factors experienced a 38% complication rate versus 4% in all others.

Conclusions

This pilot study identified pre- and peri-operative risk factors that collectively can be investigated as predictors of post-operative airway complications in a prospective study. By identifying preliminary results comparing the complication rates between those children with and without these risk factors, we will be able to calculate the sample size for a future prospective validation study. Such a study is necessary to understand the safety and potential significant cost savings of observing children without risk factors on the pediatric floor and not in an ICU setting. A best practice algorithm can be created for children with severe OSA only after completing this prospective study.     

Prepregnancy overweight and obesity are associated with impaired child neurodevelopment

The authors examined the relationship of prepregnancy body mass index (BMI) and gestational weight gain (GWG) with child neurodevelopment. Mother–child dyads were a subgroup (n = 2,084) of the Child Health and Development Studies from the Oakland, California, area enrolled during pregnancy from 1959 to 1966 and followed at child age 9 years. Linear regression was used to examine associations between prepregnancy BMI, GWG, and standardized Peabody Picture Vocabulary Test and Raven Progressive Matrices scores and to evaluate effect modification of GWG by prepregnancy BMI. Before pregnancy, 77% of women were normal weight, 8% were underweight, 11% were overweight, and 3% were obese. Associations between GWG and child outcomes did not vary by prepregnancy BMI, suggesting no evidence for interaction. In multivariable models, compared to normal prepregnancy BMI, prepregnancy overweight and obesity were associated with lower Peabody scores (b: ?1.29; 95% CI [?2.6, ?0.04] and b: ?2.7; 95% CI [?5.0, ?0.32], respectively). GWG was not associated with child Peabody score [b: ?0.03 (95% CI: ?0.13, 0.07)]. Maternal BMI and GWG were not associated with child Raven score (all P >0.05). Maternal prepregnancy overweight and obesity were associated with lower scores for verbal recognition in mid‐childhood. These results contribute to evidence linking maternal BMI with child neurodevelopment. Future research should examine the role of higher prepregnancy BMI values and the pattern of pregnancy weight gain in child cognitive outcomes.     

Primary osteoarthritis of hip, knee, and hand in relation to occupational exposure

Aim: To identify occupations with excess prevalence of osteoarthritis of the knee, hip, and hand in a nationwide survey and to compare occupations with and without excess prevalence with regard to biomechanical stresses and severity of osteoarthritis. Methods: Patients presenting with osteoarthritis of the knee, hip, or hand were recruited throughout France by their treating physician who collected information on history, including age at onset, occupation, and occupational stresses to joints. Severity was assessed using joint specific functional status questionnaires: Lequesne for the hip and knee and Dreiser for the hand. The distribution of osteoarthritis patients by occupation was compared with the distribution of occupations in all workers in France to obtain prevalence rate ratios. Results: Occupations with the greatest prevalence rate ratio were female cleaners (6.2; 95% CI 4.6 to 8.0), women in the clothing industry (5.0; 95% CI 3.9 to 6.3), male masons and other construction workers (2.9; 95% CI 2.6 to 3.3), and agriculture male and female workers (2.8; 95% CI 2.5 to 3.2). A twofold greater prevalence rate was observed within certain occupations between self-employed and salaried workers. Early onset of osteoarthritis was seen in the more heavy labour jobs with almost 40% of patients reporting their first symptoms before the age of 50. Conclusion: The early onset and severity of osteoarthritis in certain occupations warrants an urgent need for occupation specific studies for the development and evaluation of preventive strategies in this leading cause of disability in Western countries.     

Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated -7 (mda-7)/interleukin-24 (IL-24) gene

We have previously reported that overexpression of the melanoma differentiation-associated gene -7 (mda-7) using a replication-defective adenovirus (Ad-mda7), results in tumor-specific growth suppression and induction of apoptosis in wide variety of cancer cells. In the present study, we investigated the antitumor activity of Ad-mda7 and the underlying mechanism in human prostate cancer cells and normal prostate epithelial cells. Overexpression of MDA-7 induced significant (P=.001) suppression of cell growth and apoptosis in prostate cancer cells (DU 145, LNCaP, and PC-3). In normal prostate epithelial cells (PrEC) some degree of growth inhibition but not apoptosis was observed. However, the inhibitory effects in normal cells were less compared to tumor cells. Growth inhibitory effects were mediated by the intracellular and not by extracellular MDA-7 protein. Molecular effectors that are involved in Ad-mda7-mediated tumor killing included activation of the caspase cascade, and the induction of G2 phase cell cycle arrest through the inhibition of Cdc25C pathway. These results demonstrate the mechanisms by which Ad-mda7 exerts its antitumor activity in human prostate cancer cells. The antitumor activity combined with previously reported antiangiogenic and proimmune properties of Ad-mda7 can serve as a potential therapeutic agent for treatment of primary and disseminated prostate cancer.     

Arginine uptake is attenuated, through post-translational regulation of cationic amino acid transporter-1, in hyperlipidemic rats

Endothelial cell dysfunction (ECD) is a common feature of hypercholesterolemia. Defective nitric oxide (NO) generation due to decreased endothelial nitric oxide synthase (eNOS) activity is a crucial parameter characterizing ECD. L-arginine is the sole precursor for NO biosynthesis. Among several transporters that mediate L-arginine uptake, cationic amino acid transporter-1 (CAT-1) acts as a specific arginine transporter for eNOS. Our hypothesis implies that CAT-1 is a major determinant of eNOS activity in hypercholesterolemia. We studied aortic arginine uptake, CAT-1 and CAT-2 mRNA expression, and CAT-1, and PKC alpha protein in: (a) control, untreated animals (CTL), (b) rats fed with 4% cholesterol+1% cholate and 2% corn oil for 6 weeks (CHOL) and (c) rats with hypercholesterolemia treated orally with either atorvastatin (CHOL+ATORVA, 20mg/kg BW/day) or arginine 1% (CHOL+ARG) in the drinking water (modalities which have been shown to enhance CAT-1 activity and improve endothelial function). Serum cholesterol levels significantly increased in cholesterol fed animals, an increase which was blocked by atorvastatin (CTL: 66.8+/-15, CHOL: 133.9+/-22, CHOL+ARG: 128.2+/-20, CHOL+ATORVA: 77+/-15 mg/dl). Arginine transport was significantly decreased in CHOL. Treatment with neither arginine nor atorvastatin had an effect. Using RT-PCR, we found no change in aortic CAT-1 and CAT-2 mRNA expression in CHOL as well as following arginine or atorvastatin administration. The abundance of CAT-1 protein was significantly augmented in cholesterol fed rats and was not affected by arginine or atorvastatin. PKC alpha protein content, which was previously shown to regulate CAT-1 activity, increased significantly in CHOL and was neither affected by atorvastatin nor arginine. In conclusion, aortic arginine uptake is attenuated in hypercholesterolemia, through post-translational modulation of CAT-1 protein, possibly via upregulation of PKC alpha.