Arterial Spin-Labeling and DSC Perfusion Metrics Improve Agreement in Neuroradiologists' Clinical Interpretations of Posttreatment High-Grade Glioma Surveillance MR Imaging-An Institutional Experience.

BACKGROUND AND PURPOSE: MR perfusion has shown value in the evaluation of posttreatment high-grade gliomas, but few studies have shown its impact on the consistency and confidence of neuroradiologists' interpretation in routine clinical practice. We evaluated the impact of adding MR perfusion metrics to conventional contrast-enhanced MR imaging in posttreatment high-grade glioma surveillance imaging. MATERIALS AND METHODS: This retrospective study included 45 adults with high-grade gliomas who had posttreatment perfusion MR imaging. Four neuroradiologists assigned Brain Tumor Reporting and Data System scores for each examination on the basis of the interpretation of contrast-enhanced MR imaging and then after the addition of arterial spin-labeling-CBF, DSC-relative CBV, and DSC-fractional tumor burden. Interrater agreement and rater agreement with a multidisciplinary consensus group were assessed with κ statistics. Raters used a 5-point Likert scale to report confidence scores. The frequency of clinically meaningful score changes resulting from the addition of each perfusion metric was determined. RESULTS: Interrater agreement was moderate for contrast-enhanced MR imaging alone (κ = 0.63) and higher with perfusion metrics (arterial spin-labeling-CBF, κ = 0.67; DSC-relative CBV, κ = 0.66; DSC-fractional tumor burden, κ = 0.70). Agreement between raters and consensus was highest with DSC-fractional tumor burden (κ = 0.66-0.80). Confidence scores were highest with DSC-fractional tumor burden. Across all raters, the addition of perfusion resulted in clinically meaningful interpretation changes in 2%-20% of patients compared with contrast-enhanced MR imaging alone. CONCLUSIONS: Adding perfusion to contrast-enhanced MR imaging improved interrater agreement, rater agreement with consensus, and rater confidence in the interpretation of posttreatment high-grade glioma MR imaging, with the highest agreement and confidence scores seen with DSC-fractional tumor burden. Perfusion MR imaging also resulted in interpretation changes that could change therapeutic management in up to 20% of patients.

Assessment of Factors Affecting Quality of Life in Oral Squamous Cell Carcinoma Patients Using University of Washington Quality of Life Questionnaire.

Introduction Post-treatment Quality of Life (QOL) is considered an important outcome in cancer patients. A number of questionnaire tools have been designed for its assessment. University of Washington Quality of Life (UW QOL) questionnaire version four is a reliable tool for assessment of post-treatment QOL in oral squamous cell carcinoma (OSCC) patients. Our aim was to identify the post-treatment problems faced by OSCC patients and to assess the impact of clinical factors affecting post-treatment QOL by using UW QOL (version four) questionnaire. Methods The study was conducted on 59 patients with OSCC who were treated with curative intent at Patel Hospital, Karachi from August 2015 to September 2015. Patients were asked to fill the UW QOL questionnaire (version four) on their follow-up visit. Results Overall mean composite QOL score was 66.59 ± 16.98. Chewing and saliva (dryness of mouth) had the lowest scores (38.98 ± 37.2 and 56.78 ± 41.4, respectively) among all domains while pain and anxiety had the highest scores (80.93 ± 20.4 and 79.66 ± 29.8, respectively). Patients having tumors of the tongue, late stage (III and IV) tumors, and restricted mouth opening had significantly lower mean composite QOL scores. Patients with tongue tumors revealed significantly lower scores for pain, swallowing, mood, and anxiety. Patients with late-stage tumors showed significantly lower scores for chewing, swallowing, taste, saliva, appearance, anxiety, and recreation. Patients with restricted mouth opening had significantly lower scores for pain, speech, appearance, recreation, and anxiety domains. Conclusion Different clinical features have different impacts on QOL in terms of problems faced by the patients. Features having a significant effect should be identified, and measures focused on most relevant problems should be employed in order to improve the post-treatment QOL.

The Impact of Psychiatric Symptoms on Tuberous Sclerosis Complex and Utilization of Mental Health Treatment.

BACKGROUND: Tuberous sclerosis complex (TSC) is a multisystem, neurocutaneous disorder with a spectrum of TSC-associated neuropsychiatric disorders. The most common neuropsychiatric manifestations in the pediatric and adult populations are cognitive concerns, depression, and anxiety. Previous research suggests that while 90% of individuals with TSC have some TSC-associated neuropsychiatric disorders features, only 20% receive treatment, leading to a 70% treatment gap. METHODS: This web-based study used validated measures in conjunction with researcher-designed questions to evaluate perception of disease severity, presence of anxiety and depression, and the utilization and barriers toward mental health services among adults with TSC. RESULTS: The Beck Anxiety Inventory, Beck Depression Inventory-II, and Brief Illness Perception Questionnaire indicated that our overall study population had mild symptoms of anxiety, minimal depression, and a moderate perception of disease severity. Notably, the difference between the median depression score for men and women was statistically significant with men scoring higher than women (P = 0.02). Of 69 respondents, 57% (n = 39) reported receiving mental health treatment at some point over their lifetime. In both the mental health treatment group and the nonmental health treatment group, cost was more often indicated as a barrier to accessing mental health resources (treatment group: cost = 51% and stigma = 21%; nontreatment group: cost = 27% and stigma = 20%). CONCLUSIONS: TSC disease severity had a moderate and low-moderate association with anxiety and depression, respectively. Regardless of past utilization, respondents had a positive outlook towards the use of mental health services with the major barrier being cost.

Prenatal cfDNA screening results indicative of maternal neoplasm: survey of current practice and management needs.

OBJECTIVE: To determine genetic counselors' current practices and management needs for patients with prenatal cfDNA screening results indicative of maternal neoplasm. METHODS: A survey was completed by genetic counselors recruited via the National Society of Genetic Counselors (NSGC). RESULTS: Over 300 genetic counselors were surveyed. Almost all participants (95%) were aware that Noninvasive Prenatal Testing (NIPT) results may suggest maternal neoplasm, and 77% reported they would disclose such results. However, only 29% routinely communicate this possibility to patients in a pre-test setting. Management recommendations made by counselors were highly variable, and over half (51.8%) stated they would feel uncomfortable or very uncomfortable counseling a patient with these results. While less than half (44.3%) believed the current benefits of NIPT's ability to suggest maternal neoplasm outweigh its potential harms, 80.2% recognized it would be beneficial in the future. A vast majority of counselors (91.3%) felt institutional or national guidelines were needed for patient management. CONCLUSION: A majority of counselors neither felt properly equipped nor comfortable counseling patients with prenatal cfDNA results suggestive of maternal neoplasm. This study demonstrates a need for collaboration amongst clinicians, researchers, and laboratories to publish data regarding NIPT results indicative of maternal neoplasm, and for the creation of management guidelines. © 2016 John Wiley & Sons, Ltd.

Multicenter imaging outcomes study of The Cancer Genome Atlas glioblastoma patient cohort: imaging predictors of overall and progression-free survival.

BACKGROUND: Despite an aggressive therapeutic approach, the prognosis for most patients with glioblastoma (GBM) remains poor. The aim of this study was to determine the significance of preoperative MRI variables, both quantitative and qualitative, with regard to overall and progression-free survival in GBM. METHODS: We retrospectively identified 94 untreated GBM patients from the Cancer Imaging Archive who had pretreatment MRI and corresponding patient outcomes and clinical information in The Cancer Genome Atlas. Qualitative imaging assessments were based on the Visually Accessible Rembrandt Images feature-set criteria. Volumetric parameters were obtained of the specific tumor components: contrast enhancement, necrosis, and edema/invasion. Cox regression was used to assess prognostic and survival significance of each image. RESULTS: Univariable Cox regression analysis demonstrated 10 imaging features and 2 clinical variables to be significantly associated with overall survival. Multivariable Cox regression analysis showed that tumor-enhancing volume (P = .03) and eloquent brain involvement (P < .001) were independent prognostic indicators of overall survival. In the multivariable Cox analysis of the volumetric features, the edema/invasion volume of more than 85 000 mm(3) and the proportion of enhancing tumor were significantly correlated with higher mortality (Ps = .004 and .003, respectively). CONCLUSIONS: Preoperative MRI parameters have a significant prognostic role in predicting survival in patients with GBM, thus making them useful for patient stratification and endpoint biomarkers in clinical trials.

Oral administration of surfactant protein-a reduces pathology in an experimental model of necrotizing enterocolitis.

OBJECTIVES: Necrotizing enterocolitis (NEC) frequently results in significant morbidity and mortality in premature infants. Others reported that mice deficient in pulmonary surfactant protein-A (SP-A) born and raised in a nonhygienic environment succumb to significant gastrointestinal tract pathology, and enteral administration of purified SP-A significantly reduced mortality. We hypothesized that oral administration of purified SP-A can ameliorate pathology in an experimental model of neonatal NEC. METHODS: Experimental NEC was induced in newborn Sprague-Dawley rat pups by daily formula gavage and intermittent exposure to hypoxia. Purified human SP-A (5 µg/day) was administered by oral gavage. After 4 days, surviving pups were sacrificed, and intestinal pathology was assessed by histological examination of distal terminal ileal sections. Intestinal levels of inflammatory cytokines (IL-1ß, IFN-γ, and TNF-α) were assessed by enzyme-linked immunosorbent assay and levels of Toll-like receptor 4 (TLR4) by Western analysis. RESULTS: Sixty-one percent of the gavaged rat pups that survived to day 4 met the criteria for experimental NEC after hypoxia, whereas treatment with SP-A significantly reduced mortality and assessment of NEC. Intestinal levels of proinflammatory cytokines were significantly increased in pups exposed to hypoxia. Administration of SP-A to pups exposed to hypoxia significantly reduced IL-1ß and TNF-α levels, but had little effect on elevated levels of IFN-γ. SP-A treatment of hypoxia-exposed pups significantly reduced expression of intestinal TLR4, key in NEC pathogenesis. CONCLUSIONS: In a rat model of experimental neonatal NEC, oral administration of SP-A reduces intestinal levels of proinflammatory cytokines and TLR4 protein and ameliorates adverse outcomes associated with gastrointestinal pathologies.

Clinicopathologic characteristics of breast cancer in BRCA-carriers and non-carriers in women 35 years of age or less.

PURPOSE: Breast cancer diagnosed in women 35 years of age or less accounts for <2% of all breast cancer cases. Clinical and pathologic characteristics of early onset breast cancer are not well defined in BRCA mutation carriers and non-carriers. METHODS: 194 women diagnosed with breast cancer at 35 years of age or less who had BRCA1/2 mutation testing were included in the study. Logistic regression models were fit to determine the associations between clinical variables and BRCA status. RESULTS: Thirty-two (17%) and 12 (6%) patients had BRCA1 and BRCA2 mutations, respectively. BRCA1-carriers had a higher likelihood of a positive family history (FH) of breast and/or ovarian cancer (P = 0.001), or first-degree relatives diagnosed with breast cancer at <50 years old (P = 0.001) compared to non-carriers. BRCA2-carriers were more likely to have a FH of male breast cancer compared to noncarriers (P = 0.02). Among BRCA2-carriers, the age at first full-term pregnancy was younger in ER-negative cases compared with ERpositive cases (19.5 vs. 28.5 years old; P = 0.01). BRCA1-carriers with a later age at menarche were more likely to have a later stage at diagnosis (P = 0.04). Non-carriers with a lower BMI were more likely to have lymph node involvement (P = 0.03). CONCLUSIONS: Several associations were identified between reproductive risk factors or BMI and disease characteristics. Further characterization may result in a better understanding of the trends in young onset breast cancer in BRCA-carriers and non-carriers.

Endogenous osteopontin promotes ozone-induced neutrophil recruitment to the lungs and airway hyperresponsiveness to methacholine.

Inhalation of ozone (O3), a common environmental pollutant, causes pulmonary injury, pulmonary inflammation, and airway hyperresponsiveness (AHR) in healthy individuals and exacerbates many of these same sequelae in individuals with preexisting lung disease. However, the mechanisms underlying these phenomena are poorly understood. Consequently, we sought to determine the contribution of osteopontin (OPN), a hormone and a pleiotropic cytokine, to the development of O3-induced pulmonary injury, pulmonary inflammation, and AHR. To that end, we examined indices of these aforementioned sequelae in mice genetically deficient in OPN and in wild-type, C57BL/6 mice 24 h following the cessation of an acute (3 h) exposure to filtered room air (air) or O3 (2 parts/million). In wild-type mice, O3 exposure increased bronchoalveolar lavage fluid (BALF) OPN, whereas immunohistochemical analysis demonstrated that there were no differences in the number of OPN-positive alveolar macrophages between air- and O3-exposed wild-type mice. O3 exposure also increased BALF epithelial cells, protein, and neutrophils in wild-type and OPN-deficient mice compared with genotype-matched, air-exposed controls. However, following O3 exposure, BALF neutrophils were significantly reduced in OPN-deficient compared with wild-type mice. When airway responsiveness to inhaled acetyl-ß-methylcholine chloride (methacholine) was assessed using the forced oscillation technique, O3 exposure caused hyperresponsiveness to methacholine in the airways and lung parenchyma of wild-type mice, but not OPN-deficient mice. These results demonstrate that OPN is increased in the air spaces following acute exposure to O3 and functionally contributes to the development of O3-induced pulmonary inflammation and airway and lung parenchymal hyperresponsiveness to methacholine.

Self-reported reproductive health in women with tuberous sclerosis complex.

PURPOSE: Little is known about sex-specific manifestations of tuberous sclerosis complex. Inactivating mutations in the TSC1 and TSC2 genes cause tuberous sclerosis complex, and recent evidence points to a crucial role for these genes in maintaining appropriate ovarian function. The main objective of this study was to estimate reproductive dysfunction in a sample of women with tuberous sclerosis complex. METHODS: We designed a three-part questionnaire that included demographic information, reproductive history, and tuberous sclerosis complex history, and developed strict criteria to assess patterns in menstrual cyclicity; we analyzed 182 responses from female adult members of the Tuberous Sclerosis Alliance. RESULTS: More than one-third of women in our sample displayed some degree of menstrual irregularity, and their reported miscarriage rate was 41%. More than 4% of women had reproductive histories suggestive of premature ovarian insufficiency, higher than the general population estimate of 1%. CONCLUSION: Our data reveal an underappreciated aspect of tuberous sclerosis complex in affected women, suggesting that a further exploration of the role the tuberous sclerosis complex genes play in reproductive function is warranted.