Integration of Physical Examination, Old and New Biomarkers, and Ultrasonography by Using Neural Networks for Pediatric Appendicitis.

OBJECTIVE: The objective of this study was to evaluate physical examinations, imaging, and laboratory analyses individually and combined using innovative statistical analysis methods for the accurate diagnosis of pediatric appendicitis. METHODS: Patients admitted to hospital with symptoms of abdominal pain whose pediatric appendicitis scores greater than 3 were included in the study. Clinical, radiologic, and laboratory findings and as a new biomarker calprotectin (CPT) concentrations were evaluated individually and combined using artificial neural networks (ANNs), which revealed latent relationships for a definitive diagnosis. RESULTS: Three hundred twenty patients were evaluated (190 appendicitis [43 perforated] vs 130 no appendicitis). The mean ± SD age was 11.3 ± 3.6 years and 63% were male. Pediatric appendicitis scores, white blood cell (WBC) count, absolute neutrophil count (ANC), C-reactive protein (CRP) level, procalcitonin (PCT) and CPT concentrations were higher in the appendicitis group; however, only WBC and ANC were higher in first 24 hours of pain. White blood cells and CRP were diagnostic markers in patients whose appendix could not be visualized using ultrasonography (US). On classic receiver operating characteristic (ROC) analysis, the areas under the curve (AUCs) were not strong enough for differential diagnosis (WBC, 0.73; ANC, 0.72; CRP, 0.65; PCT and CPT, 0.61). However, when the physical examination, US, and laboratory findings were analyzed in a multivariate model and the ROC analysis obtained from the variables with ANN, an ROC curve could be obtained with 0.91 AUC, 89.8% sensitivity, and 81.2% specificity. C-reactive protein and PCT were diagnostic for perforated appendicitis with 0.83 and 0.75 AUC on ROC. CONCLUSIONS: Although none of the biomarkers were sufficient for an accurate diagnosis of appendicitis individually, a combination of physical examination and laboratory and US was a good diagnostic tool for pediatric appendicitis.

Osteoprotegrin interacts with biomarkers and cytokines that have roles in osteoporosis, skin fibrosis, and vasculopathy in systemic sclerosis: A potential multifaceted relationship between OPG/RANKL/TRAIL and Wnt inhibitors.

Objectives: We explored the interactions of osteoprotegerin (OPG) with biomarkers of bone turnover and cytokines, including soluble receptor activator for nuclear factor kappa beta ligand (sRANKL), tumor necrosis factor-related apoptosis-induced ligand (TRAIL), and Wnt inhibitors in osteoporosis, vasculopathy and fibrosis related to systemic sclerosis (SSc). Methods: The study included 46 SSc patients and 30 healthy controls. Skin thickness, pulmonary fibrosis and/or hypertension, digital ulcers, and calcinosis cutis of SSc patients were assessed. We determined bone mineral density (BMD), and OPG, sRANKL, TRAIL, secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), sclerostin in the serum of both patients and controls. Results: OPG, sclerostin, and sFRP-1 levels were similar between patients and controls (P > 0.05). Femoral neck and lumbar spine BMD and vitamin D levels were lower, and the OC, NTX, sRANKL, DKK1 and TRAIL levels were significantly higher, in patients than in controls (p < 0.05). In subgroup analysis, patients with higher modified Rodnan skin score (mRodnan) had higher DKK-1, sclerostin, and TRAIL levels (p < 0.05); those with diffuse SSc subtype had lower BMD values than those with limited SSc (p < 0.05). Skin and pulmonary fibrosis linked negatively with BMD measures. Conclusion: we showed that sRANKL levels were higher and correlated with bone turnover markers. It may be related to osteoporosis in SSc. The OPG level was unaltered in SSc patients. Higher TRAIL levels associated with skin thickness may indicate vascular dysfunction or injury. Higher DKK-1 and sclerostin levels may be related to a reactive increase in cells and be prominently linked to fibrosis in SSc.

Evaluation of thyroid function status among postmenopausal women with and without osteoporosis.

OBJECTIVE: To investigate the relationship between thyroid function status and bone mineral density (BMD) among women with postmenopausal osteoporosis. METHODS: A retrospective study was performed among 1217 women aged 45-80years who attended the Department of Obstetrics and Gynecology at Dokuz Eylul University, Izmir, Turkey, between August 1, 2009, and June 1, 2013. Eligible participants were grouped according to the presence or absence of osteoporosis as defined by BMD measurements at the lumbar vertebrae (L1-L4), femoral neck, or trochanter of the femur. Serum levels of free tri-iodothyronine, free tetraiodothyronine, and thyroid-stimulating hormone (TSH) were assessed. RESULTS: The 303 women with osteoporosis had a lower mean TSH level (1.8mIU/L) than did the 914 women without osteoporosis (1.9mIU/L; P=0.01). A positive correlation between TSH level and measures of BMD was observed (P=0.01). The TSH level was associated with a protective effect in a regression model for development of osteoporosis; the odds ratio was 0.68 (95% confidence interval 0.53-0.86). CONCLUSION: Osteoporosis appeared to be independently associated with serum TSH level. Maintaining TSH levels within the upper limit of the reference range during treatment of hypothyroidism could be important to prevent osteoporosis among postmenopausal women.

Does cisplatin chemotherapy decrease the MDP uptake of normal bone? An experimental study.

OBJECTIVE: Bone scan is the accepted initial imaging modality for skeletal metastases. Cisplatin is a cell-cycle nonspecific antineoplastic agent used in some chemotherapy regimens. Knowing that platinum reacts with phosphate compounds such as methylenediphosphonic acid (MDP), decreases bone resorption and new bone formation, it can be proposed that cisplatin chemotherapy may decrease Tc-99m MDP bone uptake. We aimed to demonstrate, if present, the decrease in bone uptake and to determine the duration of this effect. METHODS: Thirty male Wistar rats were randomized into five groups, namely, placebo group (G1) and cisplatin groups (G2, G3, G4, G5). Pre-therapy bone scintigraphies were obtained in all the groups. Cisplatin chemotherapy was given as infusion. Post-therapy bone scintigraphies were obtained 10 min, 1 h, 24 h, and 72 h after chemotherapy in groups G2-G5, respectively. A placebo bone scintigraphy was obtained 10 min after infusion of serum physiologic in G1. Plasma samples for cisplatin plasma values were obtained. The graphite furnace atomic absorption spectrophotometry technique was used for cisplatin analysis. Quantitative analysis (bone uptake ratios) was performed by drawing regions of interest on the right femur, vertebral column, and adjacent soft tissues. The injection/examination time delay and the net injected MDP doses were also noted. RESULTS: There was no statistically significant difference in bone uptake values, injected MDP doses or injection/examination time delay in any group. Cisplatin plasma values were significantly different in G2, G3, G4, and G5 (P < 0.05) but not in G1. CONCLUSIONS: Cisplatin chemotherapy seems to have no effect on the Tc-99m MDP uptake of normal bone.