Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants

Preterm newborns developing retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) show persistently low levels of insulin-like growth factor-I (IGF-I) in sera. They also present higher free IGF-I concentrations in epithelial lining fluids (ELFs) and lung tissues. Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that dissociates three binding proteins from the active form of IGF-I, namely free IGF-I. The present study analyzes the ELF concentrations of free IGF-I, PAPP-A, and their ratios in preterm newborns developing or not BPD, defined as O(2) dependence at 36 wk postmenstrual age. Bronchoalveolar lavage fluids of 41 infants (34 without and 7 with BPD) were analyzed on the 2nd and 4th day after birth. Infants developing BPD showed increased ELF free IGF-I and decreased PAPP-A concentrations on both days 2 and 4 compared with newborns without BPD. A nonsignificant trend between these 2 days was observed for free IGF-I (increasing) and PAPP-A (decreasing). On the same days, the free IGF-I-to-PAPP-A ratio was always significantly higher in patients developing BPD. These differences were more significant than those of IGF-I or PAPP-A when individually evaluated. A multivariate analysis confirmed the significance for free IGF-I on day 4, whereas the ratio was confirmed on both days 2 and 4. The same ratio was significantly correlated with some indexes of disease severity, such as hours of oxygen administration, days of hospitalization, and ROP severity scores. Finally, the ratio between ELF free IGF-I and PAPP-A appears to be a useful marker for lung injury of premature newborns.     

Air trapping on chest CT is associated with worse ventilation distribution in infants with cystic fibrosis diagnosed following newborn screening

Background

In school-aged children with cystic fibrosis (CF) structural lung damage assessed using chest CT is associated with abnormal ventilation distribution. The primary objective of this analysis was to determine the relationships between ventilation distribution outcomes and the presence and extent of structural damage as assessed by chest CT in infants and young children with CF.

Methods

Data of infants and young children with CF diagnosed following newborn screening consecutively reviewed between August 2005 and December 2009 were analysed. Ventilation distribution (lung clearance index and the first and second moment ratios [LCI, M₁/M₀ and M₂/M₀, respectively]), chest CT and airway pathology from bronchoalveolar lavage were determined at diagnosis and then annually. The chest CT scans were evaluated for the presence or absence of bronchiectasis and air trapping.

Results

Matched lung function, chest CT and pathology outcomes were available in 49 infants (31 male) with bronchiectasis and air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence of bronchiectasis or air trapping was associated with increased M₂/M₀ but not LCI or M₁/M₀. There was a weak, but statistically significant association between the extent of air trapping and all ventilation distribution outcomes.

Conclusion

These findings suggest that in early CF lung disease there are weak associations between ventilation distribution and lung damage from chest CT. These finding are in contrast to those reported in older children. These findings suggest that assessments of LCI could not be used to replace a chest CT scan for the assessment of structural lung disease in the first two years of life. Further research in which both MBW and chest CT outcomes are obtained is required to assess the role of ventilation distribution in tracking the progression of lung damage in infants with CF.     

Individual-level socioeconomic status is associated with worse asthma morbidity in patients with asthma

Background

Low socioeconomic status (SES) has been linked to higher morbidity in patients with chronic diseases, but may be particularly relevant to asthma, as asthmatics of lower SES may have higher exposures to indoor (e.g., cockroaches, tobacco smoke) and outdoor (e.g., urban pollution) allergens, thus increasing risk for exacerbations.

Methods

This study assessed associations between adult SES (measured according to educational level) and asthma morbidity, including asthma control; asthma-related emergency health service use; asthma self-efficacy, and asthma-related quality of life, in a Canadian cohort of 781 adult asthmatics. All patients underwent a sociodemographic and medical history interview and pulmonary function testing on the day of their asthma clinic visit, and completed a battery of questionnaires (Asthma Control Questionnaire, Asthma Quality of Life Questionnaire, and Asthma Self-Efficacy Scale). General Linear Models assessed associations between SES and each morbidity measure.

Results

Lower SES was associated with worse asthma control (F = 11.63, p < .001), greater emergency health service use (F = 5.09, p = .024), and worse asthma self-efficacy (F = 12.04, p < .01), independent of covariates. Logistic regression analyses revealed that patients with <12 years of education were 55% more likely to report an asthma-related emergency health service visit in the last year (OR = 1.55, 95%CI = 1.05-2.27). Lower SES was not related to worse asthma-related quality of life.

Conclusions

Results suggest that lower SES (measured according to education level), is associated with several indices of worse asthma morbidity, particularly worse asthma control, in adult asthmatics independent of disease severity. Results are consistent with previous studies linking lower SES to worse asthma in children, and add asthma to the list of chronic diseases affected by individual-level SES.     

Decreased tumstatin-mRNA is associated with poor outcome in patients with NSCLC

Tumstatin is a candidate tumor suppressor that plays an important role in tumor growth and angiogenesis. The purpose of this study was to evaluate the correlation between tumstatin-mRNA expression and the clinicopathologic characteristics, tumor angiogenesis, outcome of patients with non-small cell lung cancer (NSCLC). Specimens from 68 patients with NSCLC were recruited in this study. Tumstatin-mRNA expression and protein level in tumor tissues were quantified respectively by quantitative RT-PCR and ELISA. Microvessel density (MVD) was determined by CD34 immunostaining. The correlation of tumstatin-mRNA expression levels with clinicopathologic variables, tumor angiogenesis, and prognosis was analyzed. Tumstatin-mRNA expression levels were decreased in tumor. Tumstatin-mRNA expression level was significantly correlated with its protein level in tumor (r = 0.562; P = 0.001). Tumstatin-mRNA expression levels in poorly differentiated tumor tissues were significantly lower than in well-differentiated tumor tissues (P < 0.004). Furthermore, tumor tumstatin-mRNA expression were also significantly related to tumor pathologic stage (P = 0.032) and MVD (r = -0.77, P < 0.0001). Overall survival (OS) and disease-free survival (DFS) analysis indicated that NSCLC patients with low tumstatin-mRNA expression had poorer OS and DFS than those with high expression (P = 0.015 and 0.037; respectively). Multivariable Cox regression analysis revealed that the tumstatin-mRNA expression could be an independent prognostic indicators in both DFS and OS. Tumstatin-mRNA expression levels are down-regulated in NSCLC tissues. Tumstatin-mRNA expression level correlates with prognosis, which suggests that tumstatin-mRNA is a new potential independent marker of favorable prognosis in NSCLC.     

Pretreatment weight change is associated with obesity treatment outcomes

Clinical experience suggests some individuals begin obesity treatment weighing more than they did at pretreatment assessment. Weight fluctuations between baseline screening and the first treatment session were examined among individuals enrolling in a group behavioral obesity treatment outcome study. Participants (N = 480, 94% female; 28% African American; M BMI = 35.7) were classified into those who started treatment having gained weight (≥ +1.15% above screening weight), lost weight (≤ -1.15% below screening weight) or remained weight stable. The majority of participants were weight-stable (61%) during the waiting period, but 23% lost weight (-2.36 ± 1.26 kg) and 16% gained weight (+2.11 ± 1.04 kg) between baseline screening and initiating treatment. Those who lost during the pretreatment period went on to have the greatest losses at 6-months (-8.9 ± 4.9 kg), with significantly greater weight losses than either the weight-stable (-6.1 ± 5.8 kg) or the weight-gain (-5.7 ± 5.8 kg) groups. Further, those who lost weight during the waiting period went on to attend a significantly higher proportion of treatment sessions and submitted more self-monitoring diaries than those who gained weight and those who stayed weight stable while waiting. Thus, pretreatment weight change was associated with treatment outcomes and may be relevant for research screening. Further, pretreatment weight change may be a clinical marker for likely success in behavioral weight control and as such warrants additional investigation to inform potential methods for enhancing outcomes for individuals in obesity treatment.     

A C597-->A polymorphism in the Norrie disease gene is associated with advanced retinopathy of prematurity in premature Kuwaiti infants

Retinopathy of prematurity (ROP) is a retinal vascular disease which occurs in infants with a short gestational age and low birth weight and may lead to retinal detachment and blindness. In some premature infants, ROP progresses to advanced stages despite rigorous intervention, but in the majority, it spontaneously regresses before the threshold stage. Genetic factors, e.g. mutations in the Norrie disease (ND) gene, have been implicated in determining the progression of ROP to advanced stages. We have identified a novel C597A polymorphism of the ND gene; we screened this and another mutation in the ND gene, C110G, in 210 premature Kuwaiti infants using PCR-RFLP, DNA sequence analysis and DNA enzyme immunoassay hybridization to investigate their association with advanced-stage ROP. In this cohort of premature Kuwaiti newborns, 115 of 210 babies had no eye problems and served as controls, while 95 were found to have ROP. In 71 of the 95 ROP cases, the disease spontaneously regressed at or before stage 3, while in 24 of 95 ROP cases, the disease progressed to advanced stages 4 or 5. The incidence of the AA genotype of the C597A polymorphism was considerably higher in advanced-stage ROP cases (83.3%) compared to spontaneously regressing ROP cases (0%) and the normal controls (10.4%) (p < 0.0001). For the other genotypes, no significant difference was detected between the controls and ROP cases. In the case of the C110G mutation in the ND gene, no significant differences were detected between the controls and ROP cases, and the majority of subjects had a CC genotype in all three groups.     

Increased autocrine interleukin-6 production is significantly associated with worse clinical outcome in patients with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) remains incurable with current standard therapy. We have previously reported that an increased expression of interleukin-6 (IL-6) receptor CD126 leads to resistance of CLL cells to chemotherapy and worse prognosis for patients with CLL. In this study, we determine whether autocrine IL-6 production by CLL B cells is associated with poor clinical outcome and explore IL-6-mediated survival mechanism in primary CLL cells. Our results demonstrate that higher levels of autocrine IL-6 are significantly associated with shorter absolute lymphocyte doubling time, patients received treatment, without complete remission, advanced Binet stages, 17p/11q deletion, and shorter time to first time treatment and progression-free survival. IL-6 activated both STAT3 and nuclear factor kappa B (NF-κB) in primary CLL cells. Blocking IL-6 receptor and JAK2 inhibited IL-6-mediated activation of STAT3 and NF-κB. Our study demonstrates that an increased autocrine IL-6 production by CLL B-cells are associated with worse clinical outcome for patients with CLL. IL-6 promotes CLL cell survival by activating both STAT3 and NF-κB through diverse signaling cascades. Neutralizing IL-6 or blocking IL-6 receptor might contribute overcoming the resistance of CLL cells to chemotherapy. We propose that the measurement of autocrine IL-6 could be a useful approach to predict clinical outcome.     

无创辅助通气早产儿呼吸道感染病原菌分布 及影响因素分析

目的分析无创辅助通气早产儿呼吸道感染的病原菌及相关影响因素。方法选择2016年3月至2018年10月我院新生儿监护室收治的100例行无创辅助通气呼吸的早产儿为观察组。选择同期100例正常早产儿作为对照组。对两组患儿痰样本进行细菌鉴定,记录患儿基本情况并检测血中CD3~+、CD3~+/CD8~+、CD3~+/CD19~+和CD19~+/CD23~+水平。结果观察组患儿呼吸困难、发热、咳嗽、肺部喘鸣音及湿罗音发生率均高于对照组,差异有统计学意义(均P0.05)。观察组患儿血液中CD3~+、CD3~+/CD8~+水平明显低于对照组,CD3~+/CD19~+及CD19~+/CD23~+水平明显高于对照组,差异有统计学意义(均P0.05)。观察组患儿革兰阳性菌的感染率为17.00%,革兰阴性菌感染率为27.00%,其中金黄色葡萄球菌、大肠埃希菌和肺炎克雷伯菌的感染率占比相对较高。季节、通气时间、胎龄及出生体重是影响患儿呼吸道感染发生的独立性影响因素(P0.05)。结论无创辅助通气早产儿呼吸道感染病原菌以金黄色葡萄球菌、大肠埃希菌和肺炎克雷伯菌为主,季节、通气时间、胎龄及出生体重均是导致感染发生及发展的独立性影响因素。