Protein Signature of Lung Cancer Tissues

Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Risk Factors Associated with Depressive Symptoms in Caregivers of Children with Type 1 Diabetes or Cystic Fibrosis

Objective Evaluate depressive symptoms in caregivers of children with type 1 diabetes (T1D) or cystic fibrosis (CF) and identify associated risk factors. Methods A total of 195 caregivers completed demographic, stress, and depressive symptoms questionnaires. Children’s health status was obtained from medical records. Results Approximately 33% of caregivers reported elevated symptoms of depression (i.e., exceeded clinical cutoff of 16 on the Center for Epidemiological Studies-Depression Scale). For caregivers of children with T1D, elevations were associated with less caregiver education, more family stress, older child age, and worse glycemic control. For caregivers of children with CF, more family stress and lack of employment outside of the home were associated with elevated depressive symptoms. Conclusions Many caregivers of children with T1D or CF experience depressive symptoms, although risk factors may differ in these two populations. Screening of caregiver depressive symptoms as part of routine clinic visits may provide opportunities for needed intervention

Assessing diabetes-related quality of life of youth with type 1 diabetes in routine clinical care: the MIND Youth Questionnaire (MY-Q)

It is recommended to assess health-related quality of life (HRQoL) in teenagers with diabetes as part of their ongoing medical care. Here, we describe the development and psychometric evaluation of the Monitoring Individual Needs in Diabetes Youth Questionnaire (MY-Q), a multi-dimensional self-report HRQoL questionnaire designed for use in pediatric diabetes care. In expert meetings, characteristics and domains of interest were defined. Existing questionnaires were reviewed, topics selected, and new items added, resulting in the 36-item MY-Q. To test face validity, we interviewed 22 teenagers. In addition, 84 teenagers with type 1 diabetes (age 10-18 yr) completed the MY-Q and Pediatric Quality of Life Inventory (PedsQL) generic and diabetes-modules to examine psychometric properties. Hemoglobin A1c (HbA1c) values were obtained by chart audit. The MY-Q consists of seven subscales (social impact, parents, diabetes control perceptions, responsibility, worries, treatment satisfaction, and body image and eating behavior) as well as general HRQoL and emotional well-being. Cronbach's alpha for the total scale was 0.80. Strong correlations between MY-Q total and PedsQL generic and diabetes-module scores (r = 0.58 and r = 0.71, p  < 0.001) confirmed concurrent validity. Higher HbA1c was associated with lower diabetes control perceptions (r = -0.35, p = 0.001), worries (r = -0.24, p = 0.029), and body image and eating behavior (r = -0.26, p = 0.019) scores. Younger age was associated with higher diabetes control perceptions (r = -0.26, p = 0.020) and body image and eating behavior (r = -0.23, p = .038), and lower responsibility (r = 0.25, p = 0.027) scores. The MY-Q is the first HRQoL questionnaire designed for use in clinical care. It has acceptable measurement properties and seems suitable for implementation in routine care of teenagers with diabete

Type 2 diabetes mellitus among Florida children and adolescents, 1994 through 1998.

OBJECTIVES: This study was undertaken to examine the trends in the diagnosis of Type 2 diabetes mellitus among children and adolescents with new-onset diabetes seen from 1994 through 1998 at the three university-based diabetes centers in Florida. METHODS: Data were abstracted from medical records and patients were categorized as having Type 1 or Type 2 diabetes. RESULTS: There were 569 patients classified with Type 1 diabetes and 92 with Type 2 diabetes. The proportion of patients diagnosed with Type 2 diabetes increased over the five years from 9.4% in 1994 to 20.0% in 1998 (chi-square test for trend = 8.2; p=0.004). There was not an associated net increase in the total number of new diabetes patients referred over time (chi-square test for trend = 0.6, p=0.4). Those with Type 2 diabetes were more likely to have a body mass index in the 85th-94th percentile [odds ratio (OR) = 8.5; 95% confidence interval (CI) 2.5, 28.8], have a body mass index >or=95th percentile (OR = 6.8; 95% CI 2.6, 17.7), Hispanic ethnicity (OR = 6.2; 95% CI 2.2, 17.9), black race (OR = 2.8; 95% CI 1.3, 6.2), female gender (OR = 2.2; 95% CI 1.2, 4.3), and older age (OR = 1.4 for each one-year increment in age; 95% CI 1.3, 1.6), compared with those having Type 1 diabetes. CONCLUSIONS: From 1994 through 1998, there was a significant overall increase in the percentage of children referred with new-onset diabetes who were considered to have Type 2 diabetes. Factors associated with the diagnosis of Type 2 diabetes relative to Type 1 diabetes include body mass index >/=85th percentile, Hispanic ethnicity, black race, female gender, and older age