External Validation of Models for Prediction of Lymph Node Metastasis in Urothelial Carcinoma of the Bladder

Purpose

To externally validate models to predict LN metastsis; Karakiewicz nomogram, clinical nodal staging score (cNSS), and pathologic nodal staging score (pNSS) using a different cohort

Materials and Methods

Clinicopathologic data from 500 patients who underwent radical cystectomy and pelvic lymphadenectomy were analyzed. The overall predictive values of models were compared with the criteria of overall performance, discrimination, calibration, and clinical usefulness.

Results

Presence of pN+ stages was recorded in 117 patients (23.4%). Agreement between clinical and pathologic stage was noted in 174 (34.8%). Based on Nagelkerke’s peudo-R² and brier score, pNSS demonstrated best overall performance. Area under the receiver operating characteristics curve, showed that pNSS had the best discriminatory ability. In all models, calibration was on average correct (calibration-in-the-large coefficient = zero). On decision curve analysis, pNSS performed better than other models across a wide range of threshold probabilities.

Conclusions

When compared to pNSS, current precystectomy models such as the Karakiewicz nomogram and cNSS cannot predict the probability of LN metastases accurately. The findings suggest that the application of pNSS to Asian patients is feasible.     

Assessment of a Standardized Pre-Operative Telephone Checklist Designed to Avoid Late Cancellation of Ambulatory Surgery: The AMBUPROG Multicenter Randomized Controlled Trial

Objectives

To assess the impact of a standardized pre-operative telephone checklist on the rate of late cancellations of ambulatory surgery (AMBUPROG trial).

Design

Multicenter, two-arm, parallel-group, open-label randomized controlled trial.

Setting

11 university hospital ambulatory surgery units in Paris, France.

Participants

Patients scheduled for ambulatory surgery and able to be reached by telephone.

Intervention

A 7-item checklist designed to prevent late cancellation, available in five languages and two versions (for children and adults), was administered between 7 and 3 days before the planned date of surgery, by an automated phone system or a research assistant. The control group received standard management alone.

Main Outcome Measures

Rate of cancellation on the day of surgery or the day before.

Results

The study population comprised 3900 patients enrolled between November 2012 and September 2013: 1950 patients were randomized to the checklist arm and 1950 patients to the control arm. The checklist was administered to 68.8% of patients in the intervention arm, 1002 by the automated phone system and 340 by a research assistant. The rate of late cancellation did not differ significantly between the checklist and control arms (109 (5.6%) vs. 113 (5.8%), adjusted odds ratio [95% confidence interval] = 0.91 [0.65–1.29], (p = 0.57)). Checklist administration revealed that 355 patients (28.0%) had not undergone tests ordered by the surgeon or anesthetist, and that 254 patients (20.0%) still had questions concerning the fasting state.

Conclusions

A standardized pre-operative telephone checklist did not avoid late cancellations of ambulatory surgery but enabled us to identify several frequent causes.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01732159","term_id":"NCT01732159"}}NCT01732159     

Scoring System for Mortality in Patients Diagnosed with and Treated Surgically for Differentiated Thyroid Carcinoma with a 20-Year Follow-Up

Background

Differentiated thyroid carcinoma (DTC) is associated with an increased mortality. Few studies have constructed predictive models of all-cause mortality with a high discriminating power for patients with this disease that would enable us to determine which patients are more likely to die.

Objective

To construct a predictive model of all-cause mortality at 5, 10, 15 and 20 years for patients diagnosed with and treated surgically for DTC for use as a mobile application.

Design

We undertook a retrospective cohort study using data from 1984 to 2013.

Setting

All patients diagnosed with and treated surgically for DTC at a general university hospital covering a population of around 200,000 inhabitants in Spain.

Participants

The study involved 201 patients diagnosed with and treated surgically for DTC (174, papillary; 27, follicular).

Exposures

Age, gender, town, family history, type of surgery, type of cancer, histological subtype, microcarcinoma, multicentricity, TNM staging system, diagnostic stage, permanent post-operative complications, local and regional tumor persistence, distant metastasis, and radioiodine therapy.

Main outcome measure

All-cause mortality.

Methods

A Cox multivariate regression model was constructed to determine which variables at diagnosis were associated with mortality. Using the model a risk table was constructed based on the sum of all points to estimate the likelihood of death. This was then incorporated into a mobile application.

Results

The mean follow-up was 8.8±6.7 years. All-cause mortality was 12.9% (95% confidence interval [CI]: 8.3–17.6%). Predictive variables: older age, local tumor persistence and distant metastasis. The area under the ROC curve was 0.81 (95% CI: 0.72–0.91, p<0.001).

Conclusion

This study provides a practical clinical tool giving a simple and rapid indication (via a mobile application) of which patients with DTC are at risk of dying in 5, 10, 15 or 20 years. Nonetheless, caution should be exercised until validation studies have corroborated our results.     

Prediction of Post-Weaning Fibrinogen Status during Cardiopulmonary Bypass: An Observational Study in 110 Patients

Background

After cardiac surgery with cardiopulmonary bypass (CPB), acquired coagulopathy often leads to post-CPB bleeding. Though multifactorial in origin, this coagulopathy is often aggravated by deficient fibrinogen levels.

Objective

To assess whether laboratory and thrombelastometric testing on CPB can predict plasma fibrinogen immediately after CPB weaning.

Patients / Methods

This prospective study in 110 patients undergoing major cardiovascular surgery at risk of post-CPB bleeding compares fibrinogen level (Clauss method) and function (fibrin-specific thrombelastometry) in order to study the predictability of their course early after termination of CPB. Linear regression analysis and receiver operating characteristics were used to determine correlations and predictive accuracy.

Results

Quantitative estimation of post-CPB Clauss fibrinogen from on-CPB fibrinogen was feasible with small bias (+0.19 g/l), but with poor precision and a percentage of error >30%. A clinically useful alternative approach was developed by using on-CPB A10 to predict a Clauss fibrinogen range of interest instead of a discrete level. An on-CPB A10 ≤10 mm identified patients with a post-CPB Clauss fibrinogen of ≤1.5 g/l with a sensitivity of 0.99 and a positive predictive value of 0.60; it also identified those without a post-CPB Clauss fibrinogen <2.0 g/l with a specificity of 0.83.

Conclusions

When measured on CPB prior to weaning, a FIBTEM A10 ≤10 mm is an early alert for post-CPB fibrinogen levels below or within the substitution range (1.5–2.0 g/l) recommended in case of post-CPB coagulopathic bleeding. This helps to minimize the delay to data-based hemostatic management after weaning from CPB.     

The Singapore Liver Cancer Recurrence (SLICER) Score for Relapse Prediction in Patients with Surgically Resected Hepatocellular Carcinoma

Background and Aims

Surgery is the primary curative option in patients with hepatocellular carcinoma (HCC). Current prognostic models for HCC are developed on datasets of primarily patients with advanced cancer, and may be less relevant to resectable HCC. We developed a postoperative nomogram, the Singapore Liver Cancer Recurrence (SLICER) Score, to predict outcomes of HCC patients who have undergone surgical resection.

Methods

Records for 544 consecutive patients undergoing first-line curative surgery for HCC in one institution from 1992–2007 were reviewed, with 405 local patients selected for analysis. Freedom from relapse (FFR) was the primary outcome measure. An outcome-blinded modeling strategy including clustering, data reduction and transformation was used. We compared the performance of SLICER in estimating FFR with other HCC prognostic models using concordance-indices and likelihood analysis.

Results

A nomogram predicting FFR was developed, incorporating non-neoplastic liver cirrhosis, multifocality, preoperative alpha-fetoprotein level, Child-Pugh score, vascular invasion, tumor size, surgical margin and symptoms at presentation. Our nomogram outperformed other HCC prognostic models in predicting FFR by means of log-likelihood ratio statistics with good calibration demonstrated at 3 and 5 years post-resection and a concordance index of 0.69. Using decision curve analysis, SLICER also demonstrated superior net benefit at higher threshold probabilities.

Conclusion

The SLICER score enables well-calibrated individualized predictions of relapse following curative HCC resection, and may represent a novel tool for biomarker research and individual counseling.     

A Novel Admixture-Based Pharmacogenetic Approach to Refine Warfarin Dosing in Caribbean Hispanics

Aim

This study is aimed at developing a novel admixture-adjusted pharmacogenomic approach to individually refine warfarin dosing in Caribbean Hispanic patients.

Patients & Methods

A multiple linear regression analysis of effective warfarin doses versus relevant genotypes, admixture, clinical and demographic factors was performed in 255 patients and further validated externally in another cohort of 55 individuals.

Results

The admixture-adjusted, genotype-guided warfarin dosing refinement algorithm developed in Caribbean Hispanics showed better predictability (R² = 0.70, MAE = 0.72mg/day) than a clinical algorithm that excluded genotypes and admixture (R² = 0.60, MAE = 0.99mg/day), and outperformed two prior pharmacogenetic algorithms in predicting effective dose in this population. For patients at the highest risk of adverse events, 45.5% of the dose predictions using the developed pharmacogenetic model resulted in ideal dose as compared with only 29% when using the clinical non-genetic algorithm (p<0.001). The admixture-driven pharmacogenetic algorithm predicted 58% of warfarin dose variance when externally validated in 55 individuals from an independent validation cohort (MAE = 0.89 mg/day, 24% mean bias).

Conclusions

Results supported our rationale to incorporate individual’s genotypes and unique admixture metrics into pharmacogenetic refinement models in order to increase predictability when expanding them to admixed populations like Caribbean Hispanics.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01318057","term_id":"NCT01318057"}}NCT01318057     

Post-Traumatic Stress Symptoms and Post-Traumatic Growth: Evidence from a Longitudinal Study following an Earthquake Disaster

Objective

The current longitudinal study aims to examine the bidirectional relationship between post-traumatic stress symptoms (PTSS) and post-traumatic growth (PTG).

Method

One hundred twenty-two adults in the most severely affected area were investigated by self-report questionnaires at 12 months and 18 months after the Wenchuan Earthquake occurred in China.

Results

The autoregressive cross-lagged structure equation analysis revealed that PTG at 12 months post-earthquake could negatively predict PTSS at 18 months post-earthquake above and beyond PTSS stability, whereas PTSS at 12 months post-earthquake could not significantly predict subsequent PTG. Moreover, PTG at 12 months post-earthquake could predict fewer subsequent intrusions, numbing and hyper-arousal symptoms but not avoidance symptoms.

Conclusion

Growth can play a role in reducing long-term post-traumatic stress symptoms, and the implication of a positive perspective in post-trauma circumstance is discussed.     

Cancer Genetics Education in a Low- to Middle-Income Country: Evaluation of an Interactive Workshop for Clinicians in Kenya

Background

Clinical genetic testing is becoming an integral part of medical care for inherited disorders. While genetic testing and counseling are readily available in high-income countries, in low- and middle-income countries like Kenya genetic testing is limited and genetic counseling is virtually non-existent. Genetic testing is likely to become widespread in Kenya within the next decade, yet there has not been a concomitant increase in genetic counseling resources. To address this gap, we designed an interactive workshop for clinicians in Kenya focused on the genetics of the childhood eye cancer retinoblastoma. The objectives were to increase retinoblastoma genetics knowledge, build genetic counseling skills and increase confidence in those skills.

Methods

The workshop was conducted at the 2013 Kenyan National Retinoblastoma Strategy meeting. It included a retinoblastoma genetics presentation, small group discussion of case studies and genetic counseling role-play. Knowledge was assessed by standardized test, and genetic counseling skills and confidence by questionnaire.

Results

Knowledge increased significantly post-workshop, driven by increased knowledge of retinoblastoma causative genetics. One-year post-workshop, participant knowledge had returned to baseline, indicating that knowledge retention requires more frequent reinforcement. Participants reported feeling more confident discussing genetics with patients, and had integrated more genetic counseling into patient interactions.

Conclusion

A comprehensive retinoblastoma genetics workshop can increase the knowledge and skills necessary for effective retinoblastoma genetic counseling.     

Pathway Implications of Aberrant Global Methylation in Adrenocortical Cancer

Context

Adrenocortical carcinomas (ACC) are a rare tumor type with a poor five-year survival rate and limited treatment options.

Objective

Understanding of the molecular pathogenesis of this disease has been aided by genomic analyses highlighting alterations in TP53, WNT, and IGF signaling pathways. Further elucidation is needed to reveal therapeutically actionable targets in ACC.

Design

In this study, global DNA methylation levels were assessed by the Infinium HumanMethylation450 BeadChip Array on 18 ACC tumors and 6 normal adrenal tissues. A new, non-linear correlation approach, the discretization method, assessed the relationship between DNA methylation/gene expression across ACC tumors.

Results

This correlation analysis revealed epigenetic regulation of genes known to modulate TP53, WNT, and IGF signaling, as well as silencing of the tumor suppressor MARCKS, previously unreported in ACC.

Conclusions

DNA methylation may regulate genes known to play a role in ACC pathogenesis as well as known tumor suppressors.     

Anorectal Chlamydia trachomatis Load Is Similar in Men Who Have Sex with Men and Women Reporting Anal Sex

Background

Anorectal Chlamydia trachomatis (chlamydia) is frequently diagnosed in men who have sex with men (MSM) and in women, but it is unknown whether these infections are comparable in clinical impact and transmission potential. Quantifying bacterial load and identifying determinants associated with high bacterial load could provide more insight.

Methods

We selected a convenience sample of MSM who reported anal sex (n = 90) and women with concurrent urogenital/anorectal chlamydia who reported anal sex (n = 51) or did not report anal sex (n = 61) from the South Limburg Public Health Service’s STI unit. Bacterial load (Chlamydia/ml) was quantified for all samples and log transformed for analyses. Samples with an unquantifiable human leukocyte antigen (n = 9) were excluded from analyses, as they were deemed inadequately sampled.

Results

The mean log anorectal chlamydia load (3.50) was similar for MSM and women who reported having anal sex (3.80, P = 0.21). The anorectal chlamydia load was significantly higher in these groups than in women who did not report having anal sex (2.76, P = 0.001). Detectable load values ranged from 1.81–6.32 chlamydia/ml for MSM, 1.74–7.33 chlamydia/ml for women who reported having anal sex and 1.84–6.31 chlamydia/ml for women who did not report having anal sex. Symptoms and several other determinants were not associated with anorectal chlamydia load.

Conclusions

Women who did not report anal sex had lower anorectal loads, but they were within a similar range to the other two groups. Anorectal chlamydia load was comparable between MSM and women who reported anal sex, suggesting similar transmission potential.     

Quality and Cost of Diabetes Mellitus Care in Community Health Centers in the United States

Objective

To examine variations in the quality and cost of care provided to patients with diabetes mellitus by Community Health Centers (CHCs) compared to other primary care settings.

Research Design and Methods

We used data from the 2005–2008 Medical Expenditure Panel Survey (N = 2,108). We used two dependent variables: quality of care and ambulatory care expenditures. Our primary independent variable was whether the respondent received care in a Community Health Centers (CHCs) or not. We estimated logistic regression models to determine the probability of quality of care, and used generalized linear models with log link and gamma distribution to predict expenditures for CHC users compared to non-users of CHCs, conditional on patients with positive expenditures.

Results

Results showed that variations of quality between CHC users and non-CHC users were not statistically significant. Patients with diabetes mellitus who used CHCs saved payers and individuals approximately $1,656 in ambulatory care costs compared to non-users of CHCs.

Conclusions

These findings suggest an opportunity for policymakers to control costs for diabetes mellitus patients without having a negative impact on quality of care.     

Cone-Beam Computed Tomography Correlates with Conventional Helical Computed Tomography in Evaluation of Lipiodol Accumulation in HCC after Chemoembolization

Background & Aims

The amount of drug-loaded lipiodol in an HCC tumor post-transarterial chemoembolization (TACE) correlates with the risk of local tumor recurrence. Lipiodol enhancement of a tumor on conventional CT, measured in Hounsfield units (HU), can predict tumor response. Here we investigate whether cone-beam CT (CBCT) can also be used to predict tumor response, providing the benefit of being able to optimize the patient’s treatment plan intra-procedurally.

Methods

A total of 82 HCC nodules (82 patients), ≤5 cm in diameter, were treated with balloon-occluded TACE using miriplatin between December 2013 and November 2014. For each patient, both CBCT and conventional CT images were obtained post-TACE. The degree of correlation between CBCT and conventional CT was determined by comparing identical regions of interest for each imaging modality using pixel values.

Results

The pixel values from conventional CT and CBCT were highly correlated, with a Pearson correlation coefficient of 0.912 (p<0.001). The location of the nodules within the liver did not affect the results; the correlation coefficient was 0.891 (p<0.001) for the left lobe and 0.926 (p<0.001) for the right lobe. The mean pixel value for conventional CT was 439 ± 279 HU, and the mean pixel value for CBCT was 416 ± 311 HU.

Conclusions

CBCT may be used as a substitute for conventional CT to quantitatively evaluate the amount of drug-loaded lipiodol within an HCC nodule and, hence, the efficacy of TACE treatment. The major benefit of using CBCT is the ability to predict the likelihood of local recurrence intra-procedurally, enabling subsequent treatment optimization.     

Validation of Ten Noninvasive Diagnostic Models for Prediction of Liver Fibrosis in Patients with Chronic Hepatitis B

Background and Aims

Noninvasive models have been developed for fibrosis assessment in patients with chronic hepatitis B. However, the sensitivity, specificity and diagnostic accuracy in evaluating liver fibrosis of these methods have not been validated and compared in the same group of patients. The aim of this study was to verify the diagnostic performance and reproducibility of ten reported noninvasive models in a large cohort of Asian CHB patients.

Methods

The diagnostic performance of ten noninvasive models (HALF index, FibroScan, S index, Zeng model, Youyi model, Hui model, APAG, APRI, FIB-4 and FibroTest) was assessed against the liver histology by ROC curve analysis in CHB patients. The reproducibility of the ten models were evaluated by recalculating the diagnostic values at the given cut-off values defined by the original studies.

Results

Six models (HALF index, FibroScan, Zeng model, Youyi model, S index and FibroTest) had AUROCs higher than 0.70 in predicting any fibrosis stage and 2 of them had best diagnostic performance with AUROCs to predict F≥2, F≥3 and F4 being 0.83, 0.89 and 0.89 for HALF index, 0.82, 0.87 and 0.87 for FibroScan, respectively. Four models (HALF index, FibroScan, Zeng model and Youyi model) showed good diagnostic values at given cut-offs.

Conclusions

HALF index, FibroScan, Zeng model, Youyi model, S index and FibroTest show a good diagnostic performance and all of them, except S index and FibroTest, have good reproducibility for evaluating liver fibrosis in CHB patients.

Registration Number

ChiCTR-DCS-07000039.     

Resilience in the General Population: Standardization of the Resilience Scale (RS-11)

Background

The objectives of the study were to generate normative data for the RS-11 for different age groups for men and women and to further investigate the construct validity and factor structure in the general population.

Methods

Nationally representative face-to face household surveys were conducted in Germany in 2006 (n = 5,036).

Results

Normative data for the RS-11 were generated for men and women (53.7% female) and different age levels (mean age (SD) of 48.4 (18.0) years). Men had significantly higher mean scores compared with women (60.0 [SD = 10.2] vs. 59.3 [SD = 11.0]). Results of CFA supported a one-factor model of resilience. Self-esteem (standardized β = .50) and life satisfaction (standardized β =.20) were associated with resilience.

Conclusions

The normative data provide a framework for the interpretation and comparisons of resilience with other populations. Results demonstrate a special importance of self-esteem in the understanding of resilience.     

Predicting Risk of Motor Vehicle Collisions in Patients with Glaucoma: A Longitudinal Study

Purpose

To evaluate the ability of longitudinal Useful Field of View (UFOV) and simulated driving measurements to predict future occurrence of motor vehicle collision (MVC) in drivers with glaucoma.

Design

Prospective observational cohort study.

Participants

117 drivers with glaucoma followed for an average of 2.1 ± 0.5 years.

Methods

All subjects had standard automated perimetry (SAP), UFOV, driving simulator, and cognitive assessment obtained at baseline and every 6 months during follow-up. The driving simulator evaluated reaction times to high and low contrast peripheral divided attention stimuli presented while negotiating a winding country road, with central driving task performance assessed as “curve coherence”. Drivers with MVC during follow-up were identified from Department of Motor Vehicle records.

Main Outcome Measures

Survival models were used to evaluate the ability of driving simulator and UFOV to predict MVC over time, adjusting for potential confounding factors.

Results

Mean age at baseline was 64.5 ± 12.6 years. 11 of 117 (9.4%) drivers had a MVC during follow-up. In the multivariable models, low contrast reaction time was significantly predictive of MVC, with a hazard ratio (HR) of 2.19 per 1 SD slower reaction time (95% CI, 1.30 to 3.69; P = 0.003). UFOV divided attention was also significantly predictive of MVC with a HR of 1.98 per 1 SD worse (95% CI, 1.10 to 3.57; P = 0.022). Global SAP visual field indices in the better or worse eye were not predictive of MVC. The longitudinal model including driving simulator performance was a better predictor of MVC compared to UFOV (R² = 0.41 vs R² = 0.18).

Conclusions

Longitudinal divided attention metrics on the UFOV test and during simulated driving were significantly predictive of risk of MVC in glaucoma patients. These findings may help improve the understanding of factors associated with driving impairment related to glaucoma.     

A Second Look at the Association between Gender and Mortality on Antiretroviral Therapy

Objective

We assessed the association between gender and mortality on antiretroviral therapy (ART) using identical models with and without sex-specific categories for weight and hemoglobin.

Design

Cohort study of adult patients on ART.

Setting

GHESKIO Clinic in Port-au-Prince, Haiti.

Participants

4,717 ART-naïve adult patients consecutively enrolled on ART at GHESKIO from 2003 to 2008.

Main Outcome Measure

Mortality on ART; multivariable analyses were conducted with and without sex-specific categories for weight and hemoglobin.

Results

In Haiti, male gender was associated with mortality (OR 1.61; 95% CI: 1.30–2.00) in multivariable analyses with hemoglobin and weight included as control variables, but not when sex-specific interactions with hemoglobin and weight were used.

Conclusions

If sex-specific categories are omitted, multivariable analyses indicate a higher risk of mortality for males vs. females of the same weight and hemoglobin. However, because males have higher normal values for weight and hemoglobin, the males in this comparison would generally have poorer health status than the females. This may explain why gender differences in mortality are sometimes observed after controlling for differences in baseline variables when gender-specific interactions with weight and hemoglobin are omitted.     

Retroperitoneal Laparoscopic Management of Paraganglioma: A Single Institute Experience

Objectives

To explore the feasibility and safety of retroperitoneal laparoscopic resection of paraganglioma (RLPG) in a large study population.

Methods

In a six-year period, 49 patients with primary retroperitoneal paragangliomas (PG) underwent retroperitoneal laparoscopic surgery in a single center. Medical records were reviewed, and collected the following data, which were clinical characteristics, perioperative data (operative time, estimated blood loss, intraoperative hemodynamic changes, intraoperative and postoperative complications, and open conversions), and follow-up data (recurrence or distant metastases).

Results

All PGs were removed with negative tumor margin confirmed by postoperative histopathology. The operative time of RLPG was 101.59±31.12 minutes, and the estimated blood loss was 169.78±176.70ml. Intraoperative hypertensive and hypotensive episodes occurred in 25 cases and 27 cases, respectively. Two open conversions occurred. Two intraoperative complications occurred but were successfully managed endoscopically. Postoperative complications were minor and unremarkable. No local recurrence or distant metastasis were observed during the follow-up period.

Conclusions

Our experience indicates the feasibility and safety of resection of PGs in a relatively large study population.     

Prenatal Docosahexaenoic Acid Supplementation and Offspring Development at 18 Months: Randomized Controlled Trial

Objective

We evaluated the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring development at 18 months of age.

Design

Randomized placebo double-blind controlled trial.

Settings

Cuernavaca, Mexico.

Participants and Methods

We followed up offspring (n = 730; 75% of the birth cohort) of women in Mexico who participated in a trial of DHA supplementation during the latter half of pregnancy. We assessed the effect of the intervention on child development and the potential modifying effects of gravidity, gender, SES, and quality of the home environment.

Interventions or Main Exposures

400 mg/day of algal DHA.

Outcome Measures

Child development at 18 months of age measured using the Spanish version of the Bayley Scales of Infant Development-II. We calculated standardized psychomotor and mental development indices, and behavior rating scale scores.

Results

Intent-to-treat differences (DHA-control) were: Psychomotor Developmental Index -0.90 (95% CI: -2.35, 0.56), Mental Developmental Index -0.26 (95% CI: -1.63, 1.10) and Behavior Rating Scale -0.01 (95% CI: -0.95, 0.94). Prenatal DHA intake attenuated the positive association between home environment and psychomotor development index observed in the control group (p for interaction = 0.03) suggesting potential benefits for children living in home environments characterized by reduced caregiver interactions and opportunities for early childhood stimulation.

Conclusions

Prenatal DHA supplementation in a population with low intakes of DHA had no effects on offspring development at 18 months of age although there may be some benefit for infants from poor quality home environments.

Trial Registration

Clinicaltrials.gov NCT00646360     

A Novel Pre-Clinical Murine Model to Study the Life Cycle and Progression of Cervical and Anal Papillomavirus Infections

Background

Papillomavirus disease and associated cancers remain a significant health burden in much of the world. The current protective vaccines, Gardasil and Cervarix, are expensive and not readily available to the underprivileged. In addition, the vaccines have not gained wide acceptance in the United States nor do they provide therapeutic value. Papillomaviruses are strictly species specific and thus human viruses cannot be studied in an animal host. An appropriate model for mucosal disease has long been sought. We chose to investigate whether the newly discovered mouse papillomavirus, MmuPV1, could infect mucosal tissues in Foxn1^nu/Foxn1^nu mice.

Methods

The vaginal and anal canals of Foxn1^nu/Foxn1^nu mice were gently abraded using Nonoxynol-9 and “Doctor’s BrushPicks” and MmuPV1 was delivered into the vaginal tract or the anal canal.

Results

Productive vaginal, cervical and anal infections developed in all mice. Vaginal/cervical infections could be monitored by vaginal lavage. Dysplasias were evident in all animals.

Conclusions

Anogenital tissues of a common laboratory mouse can be infected with a papillomavirus unique to that animal. This observation will pave the way for fundamental virological and immunological studies that have been challenging to carry out heretofore due to lack of a suitable model system.     

18F-FDG PET-Derived Textural Indices Reflect Tissue-Specific Uptake Pattern in Non-Small Cell Lung Cancer

Purpose

Texture indices (TI) calculated from 18F-FDG PET tumor images show promise for predicting response to therapy and survival. Their calculation involves a resampling of standardized uptake values (SUV) within the tumor. This resampling can be performed differently and significantly impacts the TI values. Our aim was to investigate how the resampling approach affects the ability of TI to reflect tissue-specific pattern of metabolic activity.

Methods

18F-FDG PET were acquired for 48 naïve-treatment patients with non-small cell lung cancer and for a uniform phantom. We studied 7 TI, SUVmax and metabolic volume (MV) in the phantom, tumors and healthy tissue using the usual relative resampling (RR) method and an absolute resampling (AR) method. The differences in TI values between tissue types and cancer subtypes were investigated using Wilcoxon’s tests.

Results

Most RR-based TI were highly correlated with MV for tumors less than 60 mL (Spearman correlation coefficient r between 0.74 and 1), while this correlation was reduced for AR-based TI (r between 0.06 and 0.27 except for RLNU where r = 0.91). Most AR-based TI were significantly different between tumor and healthy tissues (pvalues <0.01 for all 7 TI) and between cancer subtypes (pvalues<0.05 for 6 TI). Healthy tissue and adenocarcinomas exhibited more homogeneous texture than tumor tissue and squamous cell carcinomas respectively.

Conclusion

TI computed using an AR method vary as a function of the tissue type and cancer subtype more than the TI involving the usual RR method. AR-based TI might be useful for tumor characterization.