Low Birth Weight Is a Risk Factor for Severe Retinopathy of Prematurity Depending on Gestational Age

Objective

To evaluate the impact of low birth weight as a risk factor for retinopathy of prematurity (ROP) that will require treatment in correlation with gestational age at birth (GA).

Study design

In total, 2941 infants born <32 weeks GA were eligible from five cohorts of preterm infants previously collected for analysis in WINROP (Weight IGF-I Neonatal ROP) from the following locations: Sweden (EXPRESS) (n = 426), North America (n = 1772), Boston (n = 338), Lund (n = 52), and Gothenburg (n = 353). Data regarding GA at birth, birth weight (BW), gender, and need for ROP treatment were retrieved. Birth weight standard deviation scores (BWSDS) were calculated with Swedish as well as Canadian reference models. Small for gestational age (SGA) was defined as BWSDS less than −2.0 SDS using the Swedish reference and as BW below the 10^th percentile using the Canadian reference charts.

Results

Univariate analysis showed that low GA (p<0.001), low BW (p<0.001), male gender (p<0.05), low BWSDS_Canada (p<0.001), and SGA_Canada (p<0.01) were risk factors for ROP that will require treatment. In multivariable logistic regression analysis, low GA (p<0.0001), male gender (p<0.01 and p<0.05), and an interaction term of BWSDS*GA group (p<0.001), regardless of reference chart, were risk factors. Low BWSDS was less important as a risk factor in infants born at GA <26 weeks compared with infants born at GA ≥26 weeks calculated with both reference charts (BWSDS_Sweden, OR = 0.80 vs 0.56; and BWSDS_Canada, OR = 0.72 vs 0.41).

Conclusions

Low BWSDS as a risk factor for vision-threatening ROP is dependent on the infant''s degree of immaturity. In more mature infants (GA ≥26 weeks), low BWSDS becomes a major risk factor for developing ROP that will require treatment. These results persist even when calculating BW deficit with different well-established approaches.     

Suicidal Feelings Interferes with Help-Seeking in Bullied Adolescents

Purpose

Being bullied is associated with the manifestation of suicidal feelings, which sharply increase in middle(-late) adolescence. Whether or not bullied middle(-late) adolescents with suicidal feelings seek help is therefore a critical issue, given that help-seeking plays a key role in the prevention of suicide. The aim of the present study is to investigate the effects of bullying, suicidal feelings and the interaction between these two factors on help-seeking behavior in adolescents.

Methods

Japanese middle(-late) adolescents (aged 15–18 years; n = 9484) were studied using self-report questionnaires. The rate of adolescents who actually sought help was examined for bullying status and suicidal feelings.

Results

The rate of adolescents who sought help was significantly higher when they were bullied (p<0.001) and also when they had mild suicidal feelings (p<0.001), but not when they displayed serious suicidal feelings. In the case of adolescents who were bullied, however, having suicidal feelings significantly decreased the rate of help-seeking (OR = 0.47, p<0.05 and OR = 0.32, p = 0.002 for having mild and serious suicidal feelings, respectively). The decrease was remarkable when suicidal feelings were serious. Specifically, the decrease was significant in seeking help from peers and family members, who are the most frequent source of the help for adolescents, when they had serious suicidal feelings (OR = 0.21, p<0.01 and OR = 0.13, p<0.001, respectively).

Conclusions

Suicidal feelings may interfere with help-seeking behavior, which could be critical in suicide prevention in bullied middle(-late) adolescents.     

Predicting Cortical Bone Strength from DXA and Dental Cone-Beam CT

Objective

This study compared the capabilities of dual-energy X-ray absorptiometry (DXA) and dental cone-beam computed tomography (CBCT) for predicting the cortical bone strength of rat femurs and tibias.

Materials and Methods

Specimens of femurs and tibias obtained from 14 rats were first scanned with DXA to obtain the areal bone mineral density (BMD) of the midshaft cortical portion of the bones. The bones were then scanned using dental CBCT to measure the volumetric cortical bone mineral density (vCtBMD) and the cross-sectional moment of inertia (CSMI) for calculating the bone strength index (BSI). A three-point bending test was conducted to measure the fracture load of each femur and tibia. Bivariate linear Pearson analysis was used to calculate the correlation coefficients (r values) among the CBCT measurements, DXA measurements, and three-point bending parameters.

Results

The correlation coefficients for the associations of the fracture load with areal BMD (measured using DXA), vCtBMD (measured using CBCT), CSMI (measured using CBCT), and BSI were 0.585 (p = 0.028) and 0.532 (p = 0.050) (for the femur and tibia, respectively), 0.638 (p = 0.014) and 0.762 (p = 0.002), 0.778 (p = 0.001) and 0.792 (p<0.001), and 0.822 (p<0.001) and 0.842 (p<0.001), respectively.

Conclusions

CBCT was found to be superior to DXA for predicting cortical bone fracture loads in rat femurs and tibias. The BSI, which is a combined index of densitometric and geometric parameters, was especially useful. Further clinical studies are needed to validate the predictive value of BSI obtained from CBCT and should include testing on human cadaver specimens.     

Blood Monocyte Chemotactic Protein-1 (MCP-1) and Adapted Disease Activity Score28-MCP-1: Favorable Indicators for Rheumatoid Arthritis Activity

Objective

We assessed blood pentraxin 3 (PTX3) and macrophage chemotactic factor-1 (MCP-1) levels as indicators of disease activity in rheumatoid arthritis (RA) patients, because data on disease activity score 28 (DAS28)-erythrocyte sedimentation rate (ESR) and DAS28-C-reactive protein (CRP) are still imperfect.

Methods

In 111 patients with RA, we examined longitudinal and cross-sectional correlations of blood PTX3, MCP-1, CRP, and ESR levels with measures of clinical arthritic activity, namely, swollen joint count (SJC), tender joint count (TJC), visual analog scale for general health (GH), DAS28, and adapted DAS28-MCP-1.

Results

Blood MCP-1, but not PTX3, was significantly correlated with SJC, TJC, DAS28, and DAS28-CRP. DAS28-MCP-1 was strongly correlated with DAS28 (r  = 0.984, P<0.001) and DAS28-CRP (r  = 0.971, P<0.001), and modestly correlated with CRP (r  = 0.350, P<0.001), and ESR (r  = 0.386, P<0.001). Similarly, the duration of arthritic symptoms, but not sex, was significantly correlated with variables of arthritic activity. In particular, DAS28-MCP-1 significantly correlated with DAS28 during a 6-month period (r  = 0.944, P<0.001; r  = 0.951, P<0.001; r  = 0.862, P<0.001; and r  = 0.865, P<0.001 for month 0, 1, 3, and 6, respectively).

Conclusion

Blood MCP-1 and adapted DAS28-MCP-1, but not blood PTX3, may be useful in monitoring RA activity.     

Relationship between Violent Behavior and Repeated Weight-Loss Dieting among Female Adolescents in Japan

Purpose

To examine whether interpersonal violence perpetration and violence toward objects are associated with body mass index (BMI), body weight perception (BWP), and repeated weight-loss dieting in female adolescents.

Methods

A cross-sectional survey using a self-report questionnaire was performed evaluating interpersonal violence perpetration, violence toward objects, the number of diets, BMI, BWP, the 12-item General Health Questionnaire (GHQ-12), victimization, substance use, and other psychosocial variables among 9,112 Japanese females aged between 12–18 years. Logistic regression analysis was conducted to analyze the contribution of BMI, BWP, and weight-control behavior to the incidence of violent behavior, while controlling for potential confounding factors.

Results

The number of diets was associated with both interpersonal violence perpetration (OR = 1.18, 95% CI 1.08–1.29, p<0.001) and violence toward objects (OR = 1.34, 95% CI 1.24–1.45, p<0.001), after adjusting for age, BMI, BWP, the GHQ-12 total score, victimization, and substance use. In terms of BMI and BWP, the “overweight” BWP was associated with violence toward objects (OR = 1.29, 95% CI 1.07–1.54, p<0.05). On the other hand, the “Underweight” and “Slightly underweight” BMI were related to violence toward objects [(OR = 1.28, 95% CI 1.01–1.62, p<0.05) and (OR = 1.27, 95% CI 1.07–1.51, p<0.05), respectively]. The “Underweight” BWP was related to interpersonal violence perpetration (OR = 2.30, 95% CI 1.38–3.84, p<0.05).

Conclusions

The cumulative number of diets is associated with violent behavior in female adolescents. In addition, underweight BMI and extreme BWP are associated with violent behavior.     

Targeting Serum Glucocorticoid-Regulated Kinase-1 in Squamous Cell Carcinoma of the Head and Neck: A Novel Modality of Local Control

Purpose

The inhibition of serum glucocorticoid-regulated kinase-1 (SGK-1) has been found to decrease growth of colon and prostate cancer cells. The purpose of this study is to evaluate the therapeutic effect of SGK-1 inhibition in head and neck squamous cell carcinoma (SCC).

Experimental Design

Human head and neck tumors (HTB41/43) were established in athymic mice. Growth rates between mice treated with vehicle (PBS) injection (group 1, n = 5), SGK-1 Inhibitor GSK 650394 (group 2, n = 6), systemic cisplatin (group 3, n = 6), and a combination of SGK-1 Inhibitor and cisplatin (group 4, n = 6) were compared using repeated measures one-way ANOVA with Newman-Keuls Multiple Comparison Test. Tumor cells were subsequently submitted to further analyses.

Results

At the end of the experiment mean tumor sizes were 122.33+/−105.86, 76.73+/−36.09, 94.52+/−75.92, and 25.76+/−14.89 mm² (mean +/− SD) for groups 1 to 4. Groups 2 and 3 showed decreased tumor growth compared to controls (p<0.001). Group 4 displayed even greater growth suppression (p<0.0001). Importantly, group 4 fared better than group 3 (p<0.001). CD44 expression was reduced in group 2 (p<0.05), and to an even greater extent in groups 3 and 4 (p<0.0025). A trend towards reduction of HER 2 expression was noted in group 4.

Conclusions

SGK-1 inhibition suppresses tumor growth, and in combination with systemic cisplatin exceeds the effect of cisplatin alone. Decreased expression of CD44 and HER 2 implies depletion of tumor stem cells, and less tumorigenicity. SGK-1 inhibition represents a potential modality of local control for palliation in advanced cases.     

Finger Position Alters the Median Nerve Properties within the Carpal Tunnel: A Pre-Post MRI Comparison Study

Purpose

The purpose of this study was to compare the properties of the median nerve and the flexor retinaculum within the carpal tunnel with Magnetic Resonance Imaging (MRI) under two conditions: (a) fingers extended, and (b) fingers in an isometric squeeze grip.

Methods

Thirty-Four volunteers participated in this experimental study. The flexor retinaculum and median nerve characteristics were measured during both conditions using MRI.

Results

The isometric squeeze grip condition resulted in significant palmar bowing of the flexor retinaculum (t = 7.67, p<.001), a significant flattening-ratio of the median nerve (t = 4.308, p<.001), and no significant decrease in the cross-sectional area of the median nerve (t = 2.508, p = 0.017).

Conclusion

The isometric squeeze grip condition resulted in anatomical deformations within the carpal tunnel, possibly explained by the lumbrical muscles incursion into the carpal tunnel during finger flexion.     

Ex Vivo Effect of Varespladib on Secretory Phospholipase A2 Alveolar Activity in Infants with ARDS

Background

Secretory phospholipase A2 (sPLA2) plays a pivotal role in acute respiratory distress syndrome (ARDS). This enzyme seems an interesting target to reduce surfactant catabolism and lung tissue inflammation. Varespladib is a specifically designed indolic sPLA2 inhibitor, which has shown promising results in animals and adults. No specific data in pediatric ARDS patients are yet available.

Methods

We studied varespladib in broncho-alveolar lavage (BAL) fluids obtained ex vivo from pediatric ARDS patients. Clinical data and worst gas exchange values during the ARDS course were recorded. Samples were treated with saline or 10–40–100 µM varespladib and incubated at 37°C. Total sPLA2 activity was measured by non-radioactive method. BAL samples were subjected to western blotting to identify the main sPLA isotypes with different sensitivity to varespladib. Results was corrected for lavage dilution using the serum-to-BAL urea ratio and for varespladib absorbance.

Results

Varespladib reduces sPLA2 activity (p<0.0001) at 10,40 and 100 µM; both sPLA2 activity reduction and its ratio to total proteins significantly raise with increasing varespladib concentrations (p<0.001). IC₅₀ was 80 µM. Western blotting revealed the presence of sPLA2-IIA and –IB isotypes in BAL samples. Significant correlations exist between the sPLA2 activity reduction/proteins ratio and PaO₂ (rho = 0.63;p<0.001), PaO₂/FiO₂ (rho = 0.7; p<0.001), oxygenation (rho = −0.6; p<0.001) and ventilation (rho = −0.4;p = 0.038) indexes.

Conclusions

Varespladib significantly inhibits sPLA2 in BAL of infants affected by post-neonatal ARDS. Inhibition seems to be inversely related to the severity of gas exchange impairment.     

Association of E/E′ and NT-proBNP with Renal Function in Patients with Essential Hypertension

Objectives

To evaluate the association of left ventricular (LV) diastolic function and N-terminal pro-brain natriuretic peptide (NT-proBNP) with renal function in essential hypertension.

Methods

LV diastolic function was estimated by the ratio of early diastolic velocities (E) from transmitral inflow to early diastolic velocities (E′) of tissue Doppler at mitral annulus (septal corner); NT-proBNP was measured in 207 hypertensive patients (mean age 56±14 years). The subjects were classified into 3 groups: E/E′≤10 group (n = 48), 10<E/E′≤15 group (n = 109) and E/E′>15 group (n = 50). The renal function was estimated by glomerular filtration rate (GFR) with ^99mTc-DTPA. GFR from 30 to 59 ml/min/1.73 m² was defined as Stage 3 chronic kidney disease (CKD). GFR was also estimated using the modified MDRD equation. Albuminuria was defined by urinary albumin/creatinine ratio (UACR).

Results

GFR was lower and UACR was higher in E/E′ >15 group than in 10< E/E′ ≤15 group or E/E′ ≤10 group (p<0.0001), GFR was significantly negative and UACR was positive correlated with E/E′ and NT-proBNP (p<0.0001). In multivariate stepwise linear analysis, GFR had significant correlation with age (p = 0.001), gender (p = 0.003), E/E′ (p = 0.03), lgNT-proBNP (p = 0.001) and lgUACR (p = 0.01), while eGFR had no significant correlation with E/E′ or lgNT-proBNP. Multivariate logistic regression analysis, adjusted for potential confounding factors, showed that participants in E/E′>15 group were more likely to have Stage 3 CKD compared with those in E/E′≤10 group with an adjusted odds ratio of 8.31 (p = 0.0036).

Conclusions

LV diastolic function, assessed with E/E′ and NT-proBNP is associated with renal function in essential hypertension.     

Reduction of Maternal Mortality with Highly Active Antiretroviral Therapy in a Large Cohort of HIV-Infected Pregnant Women in Malawi and Mozambique

Background

HIV infection is a major contributor to maternal mortality in resource-limited settings. The Drug Resource Enhancement Against AIDS and Malnutrition Programme has been promoting HAART use during pregnancy and postpartum for Prevention-of-mother-to-child-HIV transmission (PMTCT) irrespective of maternal CD4 cell counts since 2002.

Methods

Records for all HIV+ pregnancies followed in Mozambique and Malawi from 6/2002 to 6/2010 were reviewed. The cohort was comprised by pregnancies where women were referred for PMTCT and started HAART during prenatal care (n = 8172, group 1) and pregnancies where women were referred on established HAART (n = 1978, group 2).

Results

10,150 pregnancies were followed. Median (IQR) baseline values were age 26 years (IQR:23–30), CD4 count 392 cells/mm³ (IQR:258–563), Viral Load log₁₀ 3.9 (IQR:3.2–4.4), BMI 23.4 (IQR:21.5–25.7), Hemoglobin 10.0 (IQR: 9.0–11.0). 101 maternal deaths (0.99%) occurred during pregnancy to 6 weeks postpartum: 87 (1.1%) in group 1 and 14 (0.7%) in group 2. Mortality was 1.3% in women with <than 350 CD4 cells/mm³ and 0.7% in women with greater than 350 CD4s cells/mm³ [OR = 1.9 (CL 1.3–2.9) p = 0.001]. Mortality was higher in patients with shorter antenatal HAART: 22/991 (2.2%) if less than 30 days and 79/9159 (0.9%) if 31 days or greater [OR = 2.6 (CL 1.6–4.2) p<0.001]. By multivariate analysis, shorter antenatal HAART (p<0.001), baseline values for CD4 cell count (p = 0.012), hemoglobin (p = 0.02), and BMI (p<0.001) were associated with mortality. Four years later, survival was 92% for women with shorter antenatal HAART and 98% for women on established therapy prior to pregnancy, p = 0.001.

Conclusions

Antiretrovirals for PMTCT purposes have significant impact on maternal mortality as do CD4 counts and nutritional status. In resource-limited settings, PMTCT programs should provide universal HAART to all HIV+ pregnant women given its impact in prevention of maternal death.     

The Association of Uremic Toxins and Inflammation in Hemodialysis Patients

Background

Cardiovascular disease is the leading cause of mortality in hemodialysis patients and is associated with chronic inflammation. Elevation of uremic toxins, particular protein-bound uremic toxins, is a possible cause of hyper-inflammation in hemodialysis patients. But the association between uremic toxins and inflammatory markers in hemodialysis is still unclear.

Methods

We conducted a cross-sectional study to evaluate the association of the serum uremic toxins and inflammatory markers in hemodialysis patients.

Results

The uremic toxins were not associated with inflammatory markers- including high sensitivity C-reactive protein, IL(Interleukin) -1β, IL-6, tumor necrosis factor-α. In multiple linear regression, serum levels of total p-cresol sulfate (PCS) were independently significantly associated with serum total indoxyl sulfate (IS) (standardized coefficient: 0.274, p<0.001), and co-morbidity of diabetes mellitus (DM) (standardized coefficient: 0.342, p<0.001) and coronary artery disease (CAD) (standardized coefficient: 0.128, p = 0.043). The serum total PCS levels in hemodialysis with co-morbidity of DM and CAD were significantly higher than those without co-morbidity of DM and CAD (34.10±23.44 vs. 16.36±13.06 mg/L, p<0.001). Serum levels of total IS was independently significantly associated with serum creatinine (standardized coefficient: 0.285, p<0.001), total PCS (standardized coefficient: 0.239, p = 0.001), and synthetic membrane dialysis (standardized coefficient: 0.139, p = 0.046).

Conclusion

The study showed that serum levels of total PCS and IS were not associated with pro-inflammatory markers in hemodialysis patients. Besides, serum levels of total PCS were independently positively significantly associated with co-morbidity of CAD and DM.     

Impact of KRAS,BRAF, PIK3CA Mutations,PTEN, AREG,EREG Expression and Skin Rash in ≥2nd Line Cetuximab-Based Therapy of Colorectal Cancer Patients

Background

To investigate the predictive significance of KRAS, BRAF, PIK3CA mutational status, AREG- EREG mRNA expression, PTEN protein expression and skin rash in metastatic colorectal cancer (mCRC) patients treated with cetuximab containing salvage chemotherapy.

Methods

Primary tumors from 112 mCRC patients were analyzed. The worst skin toxicity during treatment was recorded.

Results

KRAS, BRAF and PIK3CA mutations were present in 37 (33%), 8 (7.2%) and 11 (9.8%) cases, respectively, PTEN was lost in 21 (19.8%) cases, AREG and EREG were overexpressed in 48 (45%) and 51 (49%) cases. In the whole study population, time to tumor progression (TTP) and overall survival (OS) was significantly lower in patients with KRAS (p = 0.001 and p = 0.026, respectively) or BRAF (p = 0.001 and p<0.0001, respectively) mutant tumors, downregulation of AREG (p = 0.018 and p = 0.013, respectively) or EREG (p = 0.002 and p = 0.004, respectively) and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively). In KRAS wt patients TTP and OS was significantly lower in patients with BRAF (p = 0.0001 and p<0.0001, respectively) mutant tumors, downregulation of AREG (p = 0.021 and p = 0.004, respectively) or EREG (p = 0.0001 and p<0.0001, respectively) and grade 0-1 skin rash (p<0.0001 and p<0.0001, respectively). TTP was significantly lower in patients with PIK3CA mutations (p = 0.01) or lost PTEN (p = 0.002). Multivariate analysis revealed KRAS (Hazard Ratio [HR] 4.3, p<0.0001), BRAF mutation (HR: 5.1, p<0.0001), EREG low expression (HR: 1.6, p = 0.021) and absence of severe/moderate skin rash (HR: 4.0, p<0.0001) as independent prognostic factors for decreased TTP. Similarly, KRAS (HR 2.9, p = 0.01), BRAF mutation (HR: 3.0, p = 0.001), EREG low expression (HR: 1.7, p = 0.021), absecence of severe/moderate skin rash (HR: 3.7, p<0.0001) and the presence of undifferantited tumours (HR: 2.2, p = 0.001) were revealed as independent prognostic factors for decreased OS.

Conclusions

These results underscore that KRAS-BRAF mutations and EREG expression can be used as biomarkers to further select patients undergoing anti-EGFR treatment.     

Poor Prognosis of Phosphatase of Regenerating Liver 3 Expression in Gastric Cancer: A Meta-Analysis

Background

Overexpression of phosphatase of regenerating liver 3 (PRL-3) has been implicated in gastric cancer (GC) metastasis. Epidemiological studies have evaluated the relationship between PRL-3 expression and prognosis in GC. However, results still remains controversial. In this study, a meta-analysis was performed to evaluate the association of PRL-3 expression with overall survival (OS) and clinicopathological characteristics.

Methods

Literature databases were searched to identify eligible studies dated until April 2013. Summary hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were calculated to estimate the association.

Results

A total of 1380 GC patients from six studies were included in the meta-analysis. Overall, the combined HR estimate for OS in a random-effect model was 1.89 (95% CI = 1.38–2.60; P<0.001). Results showed that PRL-3 overexpression was significantly associated with OS, indicating that it may be a biomarker for poor prognosis of GC. Both subgroup and sensitivity analyses further identified the prognostic role of PRL-3 expression in GC patients. Moreover, PRL-3 overexpression was significantly associated with tumor stage (OR = 2.25; 95% CI = 1.63–3.12; P<0.001), depth of invasion (OR = 2.03; 95% CI = 1.38–2.98; P<0.001), vascular invasion (OR = 2.52; 95% CI = 1.79–3.56; P<0.001), lymphatic invasion (OR = 3.74; 95% CI = 2.49–5.63; P<0.001), and lymph node metastasis (OR = 4.56; 95% CI = 2.37–8.76; P<0.001). However, when age, sex, tumor size, and tumor differentiation were considered, no obvious association was observed.

Conclusions

This meta-analysis reveals significant association of PRL-3 overexpression with OS and some clinicopathological features in GC. PRL-3 may be a predicative factor of poor prognosis and aggressive tumor behavior in GC patients.     

Poor Clinical Outcomes among Pneumonia Patients with Depressive Disorder

Background

Some studies suggested that psychological stress may be associated with the severity and duration of infectious diseases. In this population-based study, we investigated associations between depressive disorder (DD) and pneumonia outcomes in Taiwan with a large-scale database from the National Health Insurance.

Methods

Our study defined 112,198 patients who were hospitalized with a principal diagnosis of pneumonia. We defined their admission date for treatment of pneumonia as the index date. Subsequently, we selected 2,394 patients with DD within 3 years prior to their index date and 11,970 matched patients without DD. We carried out separate conditional logistic regressions to explore the association of clinical pneumonia treatment outcome (ICU admission, use of mechanical ventilation, acute respiratory failure and in-hospital death) with previously diagnosed DD.

Results

Patients with DD had a significantly higher probability of an intensive care unit admission (18.1% vs. 12.9%; p<0.001), need for mechanical ventilation (21.9% vs. 18.1%; p<0.001) and in-hospital death (10.4% vs. 9.0%; p = 0.025) than patients without DD. The study showed that pneumonia patients with DD were respectively 1.41- (95% CI: 1.25∼1.59, p<0.001), 1.28- (95% CI: 1.14∼1.43, p<0.001), and 1.17- times (95% CI: 1.01∼1.36, p = 0.039) greater odds of being admitted to the ICU, need for mechanical ventilation, and in-hospital death than patients without DD after adjusting for monthly income, urbanization level, geographic region and Charlson Comorbidity Index score.

Conclusions

In conclusion, we found that pneumonia patients with DD were associated with poor treatment outcomes compared to patients without DD.     

Pre-Treatment Anemia Is a Poor Prognostic Factor in Soft Tissue Sarcoma Patients

Background

Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery.

Methods

Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb<13 g/dl in males and Hb<12 g/dl in females according to the current WHO guidelines. The impact of pre-operative Hb levels on cancer-specific survival (CSS) and overall survival (OS) was assessed using Kaplan-Meier curves. Additionally, Hb levels were compared for the prognostic influence on CSS and OS applying univariate and multivariate Cox proportional models.

Results

Hb level was associated with established prognostic factors, including age, tumor grade, size and depth (p<0.05). Kaplan-Meier curves showed that low Hb levels were significantly associated with decreased CSS and OS in STS patients (p<0.001 for both endpoints, log-rank test). In multivariate analysis, we found an independent association between low Hb levels and poor CSS and OS (HR = 0.46, Cl 95% = 0.25–0.85, p = 0.012; HR = 0.34, Cl 95% = 0.23–0.51, p<0.001).

Conclusion

The present data underline a negative prognostic impact of low pre-operative Hb levels on clinical outcome in STS patients. Thus, Hb levels may provide an additional and cost-effective tool to discriminate between STS patients that are at high risk of mortality.     

Radiation-Induced Temporal Lobe Injury for Nasopharyngeal Carcinoma: A Comparison of Intensity-Modulated Radiotherapy and Conventional Two-Dimensional Radiotherapy

Background

To compare the radiation-induced temporal lobe injury (TLI) in patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT) or two-dimensional conventional radiotherapy (2D-CRT).

Patients and Methods

1276 cases of NPC treated with IMRT or 2D-CRT were retrospectively reviewed. A diagnosis of TLI was made on follow-up magnetic resonance imaging (MRI).

Results

The crude incidence of TLI was 7.5% and 10.8% (P = 0.048), and the actuarial 5-year incidence was 16% and 34.9% (P<0.001) for the IMRT and 2D-CRT groups, respectively. Multivariate analysis revealed both T stage (P<0.001) and radiation technique (P<0.001) as independent predictors. Patients with T1, T2 and T3 disease had a significantly higher risk when treated with 2D-CRT (P = 0.005, 0.016, <0.001, respectively). This trend was not evident for T4 patients (P = 0.680). The 2D-CRT group had a longer latency for the development of TLI (P<0.001). Those with T4 disease had a shorter median time to TLI (P = 0.006, 0.042, <0.001 when compared with T1, T2 and T3, respectively).

Conclusions

IMRT is superior to 2DRT for the management of T1-T3 NPC in terms of sparing the temporal lobe. The high incidence of TLI in T4 disease needs to be addressed.     

Factors Influencing Sleep Disturbances among Spouse Caregivers of Cancer Patients in Northeast China

Background

In China, spouse caregivers of cancer patients (SCCPs) are involved in all aspects of patient care and experience psychological distress which could result in sleep disturbance and fatigue. However, few studies have explored the differences between SCCPs and the general population, or what factors affect SCCPs'' sleep. This study aims to (1) Compare the differences in sleep disturbances and fatigue severity between SCCPs and the age- and gender-matched general population, and (2) Identify selected personal characteristics, including coping style that affect sleep disturbances in SCCPs.

Methodology/Principal Findings

The Stress and Coping Model was used to guide this study. Participants were recruited from the northeast part of China and included 600 people from the general population and 300 SCCPs. Participants completed a socio-demographic form, Fatigue Scale-14, trait Coping Style Questionnaire, and Symptom Checklist-90.

Results

The majority of the participants were middle age, most of whom (78.7%) spent more than 8 hours each day taking care of their spouses. Compared to the general population, the SCCPs experienced significant sleep disturbances with a mean of 7.30 (SD = 1.27), and fatigue severity with a mean of 8.11 (SD = 3.25). Among the selected SCCPs'' personal characteristics, current poor health status (β = 0.14, P<0.001), having a spouse under mixed treatment (β = 0.13, p<0.001), and financial burden (β = 0.14, P<0.001) are the significant predictors for sleep disturbances. Positive coping is the predictor for fewer sleep disturbances (β = 0.27, P<0.001). Those who reported sleep disturbances also experienced higher physical and mental fatigue severity (P<0.001).

Conclusion

Intervention to improve coping style in SCCPs is needed. Further research is also needed to explore the other mediators and moderators that regulate sleep disturbance and health outcomes in the SCCPs.     

Plasma Levels of Soluble Urokinase-Type Plasminogen Activator Receptor Associate with the Clinical Severity of Acute Puumala Hantavirus Infection

Objectives

Urokinase-type plasminogen activator receptor is a multifunctional glycoprotein, the expression of which is increased during inflammation. It is known to bind to β₃-integrins, which are elementary for the cellular entry of hantaviruses. Plasma soluble form of the receptor (suPAR) levels were evaluated as a predictor of severe Puumala hantavirus (PUUV) infection and as a possible factor involved in the pathogenesis of the disease.

Design

A single-centre prospective cohort study.

Subjects and Methods

Plasma suPAR levels were measured twice during the acute phase and once during the convalescence in 97 patients with serologically confirmed acute PUUV infection using a commercial enzyme-linked immunosorbent assay (ELISA).

Results

The plasma suPAR levels were significantly higher during the acute phase compared to the control values after the hospitalization (median 8.7 ng/ml, range 4.0–18.2 ng/ml vs. median 4.7 ng/ml, range 2.4–12.2 ng/ml, P<0.001). The maximum suPAR levels correlated with several variables reflecting the severity of the disease. There was a positive correlation with maximum leukocyte count (r = 0.475, p<0.001), maximum plasma creatinine concentration (r = 0.378, p<0.001), change in weight during the hospitalization (r = 0.406, p<0.001) and the length of hospitalization (r = 0.325, p = 0.001), and an inverse correlation with minimum platelet count (r = −0.325, p = 0.001) and minimum hematocrit (r = −0.369, p<0.001).

Conclusion

Plasma suPAR values are markedly increased during acute PUUV infection and associate with the severity of the disease. The overexpression of suPAR possibly activates β₃-integrin in PUUV infection, and thus might be involved in the pathogenesis of the disease.     

Pulmonary and Cardiac Function in Asymptomatic Obese Subjects and Changes following a Structured Weight Reduction Program: A Prospective Observational Study

Background

The prevalence of obesity is rising. Obesity can lead to cardiovascular and ventilatory complications through multiple mechanisms. Cardiac and pulmonary function in asymptomatic subjects and the effect of structured dietary programs on cardiac and pulmonary function is unclear.

Objective

To determine lung and cardiac function in asymptomatic obese adults and to evaluate whether weight loss positively affects functional parameters.

Methods

We prospectively evaluated bodyplethysmographic and echocardiographic data in asymptomatic subjects undergoing a structured one-year weight reduction program.

Results

74 subjects (32 male, 42 female; mean age 42±12 years) with an average BMI 42.5±7.9, body weight 123.7±24.9 kg were enrolled. Body weight correlated negatively with vital capacity (R = −0.42, p<0.001), FEV1 (R = −0.497, p<0.001) and positively with P 0.1 (R = 0.32, p = 0.02) and myocardial mass (R = 0.419, p = 0.002). After 4 months the study subjects had significantly reduced their body weight (−26.0±11.8 kg) and BMI (−8.9±3.8) associated with a significant improvement of lung function (absolute changes: vital capacity +5.5±7.5% pred., p<0.001; FEV1+9.8±8.3% pred., p<0.001, ITGV+16.4±16.0% pred., p<0.001, SR tot −17.4±41.5% pred., p<0.01). Moreover, P0.1/Pimax decreased to 47.7% (p<0.01) indicating a decreased respiratory load. The change of FEV1 correlated significantly with the change of body weight (R = −0.31, p = 0.03). Echocardiography demonstrated reduced myocardial wall thickness (−0.08±0.2 cm, p = 0.02) and improved left ventricular myocardial performance index (−0.16±0.35, p = 0.02). Mitral annular plane systolic excursion (+0.14, p = 0.03) and pulmonary outflow acceleration time (AT +26.65±41.3 ms, p = 0.001) increased.

Conclusion

Even in asymptomatic individuals obesity is associated with abnormalities in pulmonary and cardiac function and increased myocardial mass. All the abnormalities can be reversed by a weight reduction program.     

Inverse Association between Glycated Albumin and Insulin Secretory Function May Explain Higher Levels of Glycated Albumin in Subjects with Longer Duration of Diabetes

Background

Glycated albumin (GA) has been increasingly used as a reliable index for short-term glycemic monitoring, and is inversely associated with β-cell function. Because the pathophysiologic nature of type 2 diabetes (T2D) is characterized by progressive decline in insulin secretion, the aim was to determine whether GA levels were affected by diabetes duration in subjects with T2D.

Methods

To minimize the effect of glucose variability on GA, subjects with stably maintained HbA_1c levels of <0.5% fluctuation across 6 months of measurements were included. Patients with newly diagnosed T2D (n = 1059) and with duration>1 year (n = 781) were recruited and categorized as New-T2D and Old-T2D, respectively. Biochemical, glycemic, and C-peptide parameters were measured.

Results

GA levels were significantly elevated in HbA_1c-matched Old-T2D subjects compared to New-T2D subjects. Duration of diabetes was positively correlated with GA, whereas a negative relationship was found with C-peptide increment (ΔC-peptide). Among insulin secretory indices, dynamic parameters such as ΔC-peptide were inversely related to GA (r = −0.42, p<0.001). Multiple linear regression analyses showed that duration of diabetes was associated with GA (standardized β coefficient [STDβ] = 0.05, p<0.001), but not with HbA_1c (STDβ = 0.04, p<0.095). This association disappeared after additional adjustment with ΔC-peptide (STDβ = 0.02, p = 0.372), suggesting that β-cell function might be a linking factor of close relationship between duration of diabetes and GA values.

Conclusions

The present study showed that GA levels were significantly increased in subjects with longer duration T2D and with decreased insulin secretory function. Additional caution should be taken when interpreting GA values to assess glycemic control status in these individuals.