Background/Objectives: Insulin resistance is crucial in the pathogenesis of Metabolic Syndrome (MetS), type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). The triglyceride–glucose index (TyG index), a validated measure of insulin resistance, also predicts MetS, T2DM, the severity of albuminuria and ASCVD. There are scant data providing mechanistic insights into these sequalae. Accordingly, we investigated the relationship between the TyG index and biomarkers of inflammation, oxidative stress, free fatty acid (FFA) levels and adipokine dysregulation in a cohort comprising both controls and patients with nascent MetS. Methods: Participants (n = 102) included 59 patients with MetS and 43 controls. People with diabetes, ASCVD, smoking and macro-inflammation were excluded. Fasting blood was obtained for both plasma and monocyte isolation. Results: Receiver Operating Characteristic (ROC) curve analysis revealed that the TyG index was an excellent predictor of MetS with an area under the curve of 0.87, and it correlated with both hepatic and adipose tissue insulin resistance. Both serum RBP-4 levels and non-HDL cholesterol increased significantly over tertiles of the TyG index. Based on the TyG index tertiles and/or correlations, oxidized LDL, nitrotyrosine, C-reactive protein, endotoxin, chemerin, interleukin-6 levels and monocyte toll-like receptor (TLR)-4 and TLR-2 and their cellular signaling were significantly associated with the TyG index. Conclusions: Increased non-HDL-C and, most importantly, a pro-inflammatory and pro-oxidant state could be advanced as potential mechanisms explaining the increased risk for T2DM and ASCVD with an increasing TyG index.

Clinical investigators often find the thought of writing the statistical analysis plan daunting. Early collaboration between the clinical investigator and statistician can improve the study design and validity of the results by developing the statistical methodology that specifically addresses the research hypothesis. With the clinical investigator, a statistician often writes the statistical methods section that includes sample size and power analyses, randomization and blinding procedures, interim analysis, and data monitoring plans, in addition to the statistical analysis plan. To make this process less mysterious, we describe how the statistical methods section is developed in collaboration with a statistician.

The aim of this study is to review the effects of an infant’s presenting age and severity of deformation on cranial remolding orthotic (CRO) treatment outcomes for patients with deformational plagiocephaly. This study is a retrospective chart review of 499 infants with non-synostotic plagiocephaly who completed CRO treatment. Data collected included age at start of treatment, head shape measurements before and after treatment, total months of CRO treatment, and other factors such as presence/absence of prematurity. The infants were divided into subgroups according to age and severity at initiation of treatment and data for subgroups was analyzed to track the change in head shape over the course of treatment, review overall treatment duration, and discuss the rate of change of cranial deformation. Overall, treatment times tended to statistically increase with increasing initial severity and age. Posttreatment asymmetry measurements statistically trended to greater residual deformation in infants who began treatment in the older or more severe subcategories. This indicates that younger and less severe infants have shorter treatment durations and less residual cranial deformation after CRO treatment. Therefore, clinical consideration may need to be taken to treat infants at younger ages or prior to progression of the cranial deformity.

This retrospective chart review focuses on determining the most effective time to begin cranial remolding orthosis (CRO) treatment for infants with asymmetrical brachycephaly. Subjects with asymmetrical brachycephaly started CRO treatment between 3 and 18 months of age. These infants had a cranial vault asymmetry index (CVAI) ≥ 3.5 and a cranial index (CI) ≥ 90. Subjects were excluded if they had any comorbidities affecting growth, dropped out of treatment, were lost to follow-up, or were noncompliant. Factors which were found to statistically influence treatment outcomes were subject initial age, initial CVAI, and initial CI. Overall, younger subjects were more likely to achieve a corrected head shape. The presence of prematurity or torticollis had statistically nonsignificant effects on the success of treatment. Initial CI was found to be a stronger predictor than initial CVAI as to which subjects achieved correction. The less severe the starting CI, the more likely the subject was to achieve full correction. The clinical understanding is that it requires more cranial growth to “round out” a full posterior skull flattening than an asymmetry. Based on the study results, infants with asymmetrical brachycephaly should be treated as early as possible to increase chances of achieving full correction of the deformity.

This placebo-controlled randomized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women, 57 of whom were early postmenopausal (five years after menopause) and six of whom were mid-postmenopausal (five to ten years after menopause). Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years. The two groups were similar in baseline age, years postmenopause (3.3 in the calcium citrate group vs 2.7 in the placebo group), height, weight, calcium intake, and L2-L4 bone density. L2-L4 bone density did not change during calcium citrate treatment (+ 1.03% after two years), whereas it declined significantly by -2.38% after two years on placebo (P < .001). Femoral neck bone density did not change in either group. Radial shaft bone density did not change in the calcium citrate group (-0.02% after two years), but it declined significantly in the placebo group (-1.79% after one year and -3.03% after two years, P < .01). The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups. An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause, but a protective effect after three years. Although serum PTH did not change, serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group, indicative of parathyroid suppression. Serum bone-specific alkaline phosphatase and osteocalcin, and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods, indicative of a reduction in bone turnover. Thus, calcium citrate supplementation (400 mg of calcium twice daily) averted bone loss and stabilized bone density in the spine, femoral neck, and radial shaft in women relatively soon after menopause. This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression.