Background: Weight in infancy correlates with risk of type 2 diabetes, hypertension, and obesity in adulthood. Clinical observations have been confounded by obesity-prone genotypes and obesity-linked lifestyles. Objectives: To define the effects of isolated neonatal macrosomia in isogenic animals, we compared macrosomic and control C57Bl6 mice co-fostered by healthy dams receiving standard laboratory feed. Methods: Naturally occurring neonatal macrosomia was identified by a gender-specific weanling weight above the 90th percentile for the colony. Macrosomic and control mice were phenotyped in adulthood by exercise wheel, tail cuff and intraperitoneal insulin or glucose challenge. Results: Compared to control males, adult males with a history of neonatal macrosomia had significantly increased body weight, reduced voluntary activity, insulin resistance, fasting hyperinsulinemia, and impaired glucose tolerance. In contrast, adult females with neonatal macrosomia had no significant alteration in body weight or endocrine phenotypes, but did have higher blood pressures and lower heart rates than control females. After these baseline studies, all mice were switched to a hypercaloric, high fat diet (5 kcal/g, 45% of energy as fat). Twenty weeks later, male mice had impaired glucose tolerance and insulin resistance, independent of their weanling weight classification. While on high fat feeds, macrosomic males maintained a significantly higher body weight than control males. Conclusions: We conclude that (1) in our murine model, neonatal macrosomia is an independent risk factor of adult metabolic syndrome, and (2) neonatal macrosomia accentuates the sexually dimorphic predisposition of C57Bl6 male mice towards glucose intolerance and C57Bl6 female mice towards hypertension.

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Stereotactic body radiation therapy (SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer (NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility, prescription dose and delivery, and follow up duration varied widely. Three-years overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.

Premature infants are at increased risk for persistent growth failure, neurodevelopmental impairment, hypertension, and diabetes. Rapid neonatal growth has been linked to the increasing prevalence of diabetes and obesity. Nutritional goals for the premature infant with incipient growth failure have thus become a source of controversy. We used isogenic mice with natural variation in perinatal growth to test the hypothesis that neonatal catch up growth improves the neurobehavioral and cardiovascular outcomes of lowbirth weight mice, despite an increase in diabetes susceptibility. Adult mice that experienced prenatal and neonatal growth restriction had persistent growth failure, hypertension, and neurobehavioral alterations. When switched from standard rodent chow to a hypercaloric diet, growth restricted mice were protected from diet-induced obesity. Among low-birth weight male mice, neonatal catch up growth normalized neurobehavioral and cardiovascular phenotypes, but led to insulin resistance and high fat diet-induced diabetes. Among low-birth weight female mice, neonatal catch up growth did not prevent the development of adult hypertension and significantly increased measures of anxiety, including self-injury and the avoidance of open spaces. These studies support the importance of the perinatal environment in the resetting of adult disease susceptibility and suggest an earlier window of vulnerability among growth restricted female mice. (Pediatr Res 66: 53-58, 2009) R estricted perinatal growth is an independent risk factor for the development of type 2 diabetes, hypertension, and coronary heart disease (1,2). The primary animal models of programmed adult disease induce fetal growth restriction through maternal nutrient restriction or uterine artery ligation (3). The development of diabetes and obesity in these models has been most dramatic when rodent pups are cross-fostered to well-nourished dams and then weaned to postnatal high-fat diets (4,5). These studies are consistent with epidemiologic data linking excessive weight gain in infancy with adult metabolic syndrome (6). Although these data suggest that restriction of neonatal nutrition might improve adult metabolic health, a comprehensive approach is essential when considering the long-term consequences of perinatal dietary alterations (7).Preterm delivery increases the risk of impaired growth during a critical window of brain development. By 36-wk postmenstrual age, ϳ90% of premature infants have growth failure (weight less than the 10th percentile of reference fetuses) (8). This perinatal growth failure is associated with permanent reductions in adult weight and height (9). It follows that premature delivery greatly increases the risk of neurodevelopmental impairment, insulin resistance, and adult hypertension (10 -12). As parallel epidemics of prematurity and obesity unfold, there is a critical need for research-based neonatal nutritional recommendations that seek to optimize short-term health and long-term outcomes.We previously evaluated th...

Background The objective of the current study was to compare the safety and efficacy between 2 analgesic regimens for patients with head and neck cancer (HNC) undergoing definitive chemoradiation (CRT). Methods The current study was a prospective, single‐institution, 2‐arm, randomized pilot study. Patients with American Joint Committee on Cancer seventh edition stage II to stage IV squamous cell carcinoma of the head and neck who were undergoing CRT were randomized to either arm 1, which entailed high‐dose gabapentin (2700 mg daily) with the institutional standard of care (hydrocodone and/or acetaminophen progressing to fentanyl as needed), or arm 2, which comprised low‐dose gabapentin (900 mg daily) with methadone. The primary endpoints were safety and toxicity. Secondary endpoints were pain, opioid requirement, and quality of life (QOL). Differences between the treatment arms at multiple time points were compared using a generalized linear mixed regression model with Sidak correction. Results A total of 60 patients (31 in arm 1 and 29 in arm 2) were enrolled from April 2015 to August 2017. There was no difference between the treatment arms with regard to adverse events or serious adverse events. Pain was not found to be different between the treatment arms. More patients in arm 1 did not require an opioid during treatment (42% vs 7%; P = .002). Patients in arm 2 experienced significantly better QOL outcomes across multiple domains, including overall health (P = .05), physical functioning (P = .04), role functioning (P = .01), and social functioning (P = .01). Conclusions High‐dose prophylactic gabapentin increased the percentage of patients who required no opioid during treatment. Methadone may improve QOL compared with a regimen of short‐acting opioids and fentanyl. However, pain was found to significantly worsen throughout treatment regardless of treatment arm, necessitating further studies to identify a more optimal regimen.