Well-Child Visits for Early Detection and Management of Maternal Postpartum Hypertensive Disorders.

Importance: Innovative approaches are needed to address the increasing rate of postpartum morbidity and mortality associated with hypertensive disorders. Objective: To determine whether assessing maternal blood pressure (BP) and associated symptoms at time of well-child visits is associated with increased detection of postpartum preeclampsia and need for hospitalization for medical management. Design, Setting, and Participants: This is a pre-post quality improvement (QI) study. Individuals who attended the well-child visits between preimplementation (December 2017 to December 2018) were compared with individuals who enrolled after the implementation of the QI program (March 2019 to December 2019). Individuals were enrolled at an academic pediatric clinic. Eligible participants included birth mothers who delivered at the hospital and brought their newborn for well-child check at 2 days, 2 weeks, and 2 months. A total of 620 individuals were screened in the preintervention cohort and 680 individuals were screened in the QI program. Data was analyzed from March to July 2022. Exposures: BP evaluation and preeclampsia symptoms screening were performed at the time of the well-child visit. A management algorithm-with criteria for routine or early postpartum visits, or prompt referral to the obstetric emergency department-was followed. Main Outcome and Measures: Readmission due to postpartum preeclampsia. Comparisons across groups were performed using a Fisher exact test for categorical variables, and t tests or Mann-Whitney tests for continuous variables. Results: A total of 595 individuals (mean [SD] age, 27.2 [6.1] years) were eligible for analysis in the preintervention cohort and 565 individuals (mean [SD] age, 27.0 [5.8] years) were eligible in the postintervention cohort. Baseline demographic information including age, race and ethnicity, body mass index, nulliparity, and factors associated with increased risk for preeclampsia were not significantly different in the preintervention cohort and postintervention QI program. The rate of readmission for postpartum preeclampsia differed significantly in the preintervention cohort (13 individuals [2.1%]) and the postintervention cohort (29 individuals [5.6%]) (P = .007). In the postintervention QI cohort, there was a significantly earlier time frame of readmission (median [IQR] 10.0 [10.0-11.0] days post partum for preintervention vs 7.0 [6.0-10.5] days post partum for postintervention; P = .001). In both time periods, a total of 42 patients were readmitted due to postpartum preeclampsia, of which 21 (50%) had de novo postpartum preeclampsia. Conclusions and Relevance: This QI program allowed for increased and earlier readmission due to postpartum preeclampsia. Further studies confirming generalizability and mitigating associated adverse outcomes are needed.

Non-invasive prenatal screening: Testing motivations and decision making in the low-risk population.

Non-invasive prenatal screening provides a risk assessment for aneuploidies by utilizing cell-free DNA (cfDNA). It is recommended that cell-free DNA screening (cfDNA screening) be offered to all pregnant people regardless of a priori risk for aneuploidy. In the absence of an increased risk, alternative motives for electing cfDNA screening and different levels of informed decision making may arise. Therefore, our study aimed to characterize low-risk patients' motivations for cfDNA screening election, determine how often informed decisions are being made, and compare motivations between informed and uninformed decision makers. A survey that included a modified, validated measure of informed choice (MMIC) and questions to assess patients' motivations for cfDNA screening was offered at four MFM clinics following genetic counseling. It was found that 44% of participants (n = 100) made an uninformed decision about testing. Participants with private insurers were 4.25 times more likely to make an informed decision (95% CI = 1.10-16.37). Informed decision makers scored avoiding invasive procedures higher (p = 0.007) and ranked doing what family/friends desire lower (p = 0.005) than uninformed decision makers. While most participants scored receiving information about genetic conditions highest, 12% of participants reported fetal sex disclosure as a priority. However, this was not found to be associated with uninformed decision making. This study ultimately established that following genetic counseling, a low-risk population shared motivations with high-risk populations which highlights the importance of complete pre-test counseling for all. Future research should investigate the effect of modifying variables, such as socioeconomic status, on the performance of informed choice measures and critically evaluate the parameters that determine informed choice.

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.

Thoracic and Lumbosacral Spine Anatomy.

We review anatomy of the thoracic, lumbar, and sacral spine. Knowledge of normal anatomy is vital when reviewing imaging of the spine because it allows for the detection of abnormal findings. We emphasize the normal appearance of the thoracic and lumbosacral spine on imaging, focusing on the most common imaging techniques of computed tomography and magnetic resonance imaging, as well as highlighting a few less common and emerging imaging techniques that can evaluate the spine.

Anatomy of the Spinal Cord, Coverings, and Nerves.

The spinal cord is an elegant structure that serves as a conduit for the transfer of information between the brain and the peripheral nervous system. To enable the reader to understand its complex microstructural anatomy, we have created a detailed yet approachable anatomic reference for clinicians. We review gross and structural features of the spinal cord, its coverings, and nerves while also discussing spinal cord development, microscopic organization, and common anatomic variants. We detail how this anatomy appears on current neuroimaging techniques, with special attention to MR imaging.

Ototoxicity of Topical Antibiotic Ear Drops in Chronic Suppurative Otitis Media in Humans: A Review of the Literature.

An electronic search of the literature was performed for reported cases of ototoxicity associated with the use of topical antibiotic ear drops in humans. The dosage, duration, and type of ototoxic preparations involved were recorded. Due to the scant quantity of low-quality information that is currently available, there was uncertainty about the usefulness of topical antibiotics in enhancing the resolution of ear discharge in patients with chronic suppurative otitis media. However, despite this uncertainty, there are some data to show that using topical antibiotics in comparison to a placebo or in conjunction with a systemic antibiotic may be useful. Additionally, there is ambiguity regarding the relative efficacy of various kinds of antibiotics; it is impossible to say with absolute certainty whether quinolones are superior to or inferior to aminoglycosides. Although the adverse impact profiles of these two classes of chemicals varied, there are not enough data from the included trials to draw any conclusions about them. Negative effects were generally underreported.

Imaging anatomy of the vertebral canal for trans-sacral hiatus puncture of the lumbar cistern.

A standard lumbar puncture may be impossible for many anatomic or technical reasons. Previous accounts of caudal epidural anesthesia and other procedures via the sacral hiatus prompted us to test if image-guided percutaneous trans-sacral hiatus access to the lumbosacral subarachnoid cistern would be anatomically feasible. To study vertebral canal morphometry and curvature, we analyzed midsagittal computed tomography-myelogram images of 40 normal subjects and digitally measured sacral curvatures between S1 to S5 and S2 to S4 using two methods whereby a lower angle signifies a straighter sacrum. We measured midsagittal vertebral canal area, hiatus width, dural sac termination levels, and distance from sacral hiatus to the dural sac tip (needle distance). Subjects were F:M = 25:15, with a mean age of 44.9 years. The two S1-S5 full sacral curvature mean angles were 57.3° and 60.4°. Almost all sacral hiatuses were at S4, and dural sac terminations were at S1-S2. The mean S2-S4 sacral curvature was 25.1°, and the mean needle distance was 57.7 mm. Using two-way analysis of variance, there were significant sex differences for needle distances (p = .001), and full and limited sacral curvatures (p = .02, and p = .046, respectively). There were no significant linear regression correlations between age and sacral curvature, needle distance, canal area, or hiatus width. Therefore, despite a frequently prominent full sacral curvature, the combination of S1-S2 dural sac termination plus a relatively straight trajectory of the lower vertebral canal between S2 and S4 support the theoretical feasibility of percutaneous trans-sacral hiatus and vertebral canal access to the lumbosacral cistern using a standard spinal needle.

Exploring the predicted yield of prenatal testing by evaluating a postnatal population with structural abnormalities using a novel mathematical model.

OBJECTIVE: To determine the yield of prenatal testing and screening options after identification of fetal structural abnormalities using a novel mathematical model. METHOD: A retrospective chart review was conducted to collect structural abnormality and genetic testing data on infants who were evaluated postnatally by a medical geneticist. A novel mathematical model was used to determine and compare the predicted diagnostic yields of prenatal testing and screening options. RESULTS: Over a quarter of patients with at least one structural abnormality (28.1%, n = 222) had a genetic aberration identified that explained their phenotype. Chromosomal microarray (CMA) had the highest predicted diagnostic yield (26.8%, P < .001). Karyotype (20.8%) had similar yields as genome wide NIPT (21.2%, P = .859) and NIPT with select copy number variants (CNVs) (17.9%, P = .184). Among individuals with an isolated structural abnormality, whole exome sequencing (25.9%) and CMA (14.9%) had the highest predicted yields. CONCLUSION: This study introduces a novel mathematical model for predicting the potential yield of prenatal testing and screening options. This study provides further evidence that CMA has the highest predicted diagnostic yield in cases with structural abnormalities. Screening with expanded NIPT options shows potential for patients who decline invasive testing, but only in the setting of adequate pre-test counseling.

The impact of genetic counseling on women's grief and coping following termination of pregnancy for fetal anomaly.

Pregnancy termination for fetal anomaly (TFA) is a unique experience that can cause women to develop long-term complicated grief. Although a woman's experience with her healthcare providers has been previously identified as an important factor in coping, studies have shown that many women report their health care as lacking to some extent. Given the overlap in women's needs and the practice scope of a genetic counselor (GC), this study aimed to examine how genetic counseling may impact coping and explore women's expectations of GCs pre- and post-TFA. An online survey, which included the brief COPE and the short version of the Perinatal Grief Scale, was distributed among private online support groups. Appropriate statistical analysis tools, such as the Wilcoxon rank-sum and t test, were utilized for quantitative analysis of the 124 responses, and inductive content analysis was utilized for qualitative analysis. Of those who underwent TFA within the last two years, women who saw a GC utilized active coping, planning, and positive reframing significantly more than women who did not see a GC (p = 0.001, p = 0.031, p = 0.027, respectively). GCs were perceived to have a positive impact on coping when providing information, objective care, emotional support, support resources, and follow-up care; these practices encouraged confidence in their personal decision-making and gave women hope for the future. This study not only identified key counseling roles for GCs prior to a TFA, but also demonstrated that genetic counseling prior to TFA may be beneficial to coping. Further studies are warranted to explore the needs of a more diverse population and to identify appropriate genetic counseling training methods to support women pursuing TFA.

Examining genetic counselors' implicit attitudes toward disability.

Genetic counselors have a unique role in healthcare that requires a balance between being a patient educator and patient advocate when discussing disability. This study aimed to determine genetic counselors' implicit attitudes toward disability, and identify what factors affect these implicit attitudes. Case scenarios involving disability were used to examine hypothetical estimates of time spent on different topics within a genetic counseling session. Implicit attitudes were measured using the validated Disability Attitudes Implicit Association Test (DA-IAT), and personal/professional experiences with disability were assessed. Analysis of 382 respondents of the electronic survey revealed that personal experience with individuals with disabilities was not significantly associated with implicit attitudes scores. In addition, results demonstrated that genetic counselors have a stronger bias toward ability (Dmean  = 0.62, Dstd  = ±0.45) compared to previous participants of the DA-IAT (p < .005). Practice specialty, length of time in the genetic counseling field, or whether the participant was a practicing counselor or genetic counseling student were not associated with implicit attitudes scores. The bias toward ability observed across practice specialties may be due to shared factors that influence interest in this field, but may also potentially reflect the inability of the DA-IAT to capture the complexity of genetic counselors' relationship to individuals with disability. This study emphasizes the importance of incorporating patients' individual definitions of disability into genetic counseling sessions and building an environment of patient advocacy and education around their personal perspectives and needs.

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.

Role of prophylactic azithromycin to reduce airway inflammation and mortality in a RSV mouse infection model.

BACKGROUND: Respiratory syncytial virus (RSV) infection is an important cause of morbidity and mortality in vulnerable populations. Macrolides have received considerable attention for their anti-inflammatory actions beyond their antibacterial effect. We hypothesize that prophylactic azithromycin will be effective in reducing the severity of RSV infection in a mouse model. METHODS: Four groups of BALB/c mice were studied for 8 days: Control (C), RSV-infected (R), early prophylaxis with daily azithromycin from days 1 to 8, (E), and late prophylaxis with daily azithromycin from days 4 to 8 (L). Mice were infected with RSV on day 4, except for the control group. All groups were followed for a total of 8 days when bronchoalveolar lavage cell count and cytokines levels were measured. Mouse weight, histopathology, and mortality data were obtained. RESULTS: Prophylactic azithromycin significantly attenuated post-viral weight loss between group R and both groups E and L (P = 0.0236, 0.0179, respectively). IL-6, IL-5, and Interferon-Gamma were significantly lower in group L (P = 0.0294, 0.0131, and 0.0056, respectively) compared with group R. The total cell count was significantly lower for group L as compared with group R (P < 0.05). Mortality was only observed in group R (8%). Lung histology in the prophylactic groups showed diminished inflammatory infiltrates and cellularity when compared with group R. CONCLUSION: Prophylactic azithromycin effectively reduced weight loss, airway inflammation, cytokine levels and mortality in RSV-infected mice. These results support the rationale for future clinical trials to evaluate the effects of prophylactic azithromycin for RSV infection.

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.

Support Desired by Women Following Termination of Pregnancy for a Fetal Anomaly.

With the rapidly evolving field of prenatal testing, there is a growing need to provide support for women pursuing termination of pregnancy following the discovery of a fetal anomaly. Previous studies have documented that women in this situation often feel unsupported, but the type of resources desired by this population remains undetermined. We studied the awareness and utilization of support resources in 51 women at the time of the procedure, at 6 weeks, and at 3 months following the event. Though largely knowledgeable of existing resources at the time of the procedure, only 50 % admitted contemplating their individualized need for support. Most expected to rely on the support of family and friends. Additionally, 50 % expressed the desire to commemorate the pregnancy, though none wanted direct contact with their healthcare provider(s). Responses from the 6 weeks and 3 months assessments were consistent with previous literature as many women indicated not coping as expected and were unprepared for the psychological consequences following the procedure. Our findings indicate that women in these situations may not realize what their long-term support needs will be. They further indicate that guidelines for routine follow-up care should be established among healthcare providers that respect this population's initial desires to avoid reminders of the pregnancy and promote a flexible timeframe for support uptake. Additional support resources that promote flexible uptake as well as meet the desires of anonymity and ease of access need to be developed for this population.

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.

Effect of antigen sensitization and challenge on oscillatory mechanics of the lung and pulmonary inflammation in obese carboxypeptidase E-deficient mice.

Atopic, obese asthmatics exhibit airway obstruction with variable degrees of eosinophilic airway inflammation. We previously reported that mice obese as a result of a genetic deficiency in either leptin (ob/ob mice) or the long isoform of the leptin receptor (db/db mice) exhibit enhanced airway obstruction in the presence of decreased numbers of bronchoalveolar lavage fluid (BALF) eosinophils compared with lean, wild-type mice following antigen (ovalbumin; OVA) sensitization and challenge. To determine whether the genetic modality of obesity induction influences the development of OVA-induced airway obstruction and OVA-induced pulmonary inflammation, we examined indices of these sequelae in mice obese as a result of a genetic deficiency in carboxypeptidase E, an enzyme that processes prohormones and proneuropeptides involved in satiety and energy expenditure (Cpe(fat) mice). Accordingly, Cpe(fat) and lean, wild-type (C57BL/6) mice were sensitized to OVA and then challenged with either aerosolized PBS or OVA. Compared with genotype-matched, OVA-sensitized and PBS-challenged mice, OVA sensitization and challenge elicited airway obstruction and increased BALF eosinophils, macrophages, neutrophils, IL-4, IL-13, IL-18, and chemerin. However, OVA challenge enhanced airway obstruction and pulmonary inflammation in Cpe(fat) compared with wild-type mice. These results demonstrate that OVA sensitization and challenge enhance airway obstruction in obese mice regardless of the genetic basis of obesity, whereas the degree of OVA-induced pulmonary inflammation is dependent on the genetic modality of obesity induction. These results have important implications for animal models of asthma, as modeling the pulmonary phenotypes for subpopulations of atopic, obese asthmatics critically depends on selecting the appropriate mouse model.

Dysanaptic growth of lung and airway in children with post-infectious bronchiolitis obliterans.

RATIONALE: Post-infectious bronchiolitis obliterans (PBO) is a rare form of chronic obstructive lung disease associated with small airway fibrosis following a severe insult to the lower respiratory tract. It has been suggested that PBO is a non-progressive disease. However, evidence supporting this statement is limited. In this case series, we sought to determine the changes of pulmonary function tests (PFT) over time in children with PBO. METHODS: Seven children with PBO, ages 6-15 years old, were retrospectively studied between 1994 and 2012. Spirometry and lung volumes tests were performed in accordance with American Thoracic Society (ATS) guidelines and were monitored over time. The average rate of change was calculated using generalized linear mixed models. RESULTS: The median baseline values for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), the FEV1/FVC ratio and forced expiratory flow 25%-75% (FEF25%-75%) were 57%, 50%, 87% and 29%, respectively. FVC increased at a rate of 1.8% per year (P = 0.008). There was no significant change in FEV1 over time (P = 0.112). However, the FEV1/FVC ratio decreased by 2.6% per year (P < 0.001). CONCLUSION: PFT in childhood PBO was characterized by significant airway obstruction. Over time, FVC (lung parenchyma) increased and FEV1 (airway) remained stable, but FEV1/FVC ratio declined more than expected, suggesting a mismatch in the growth of the airway and lung parenchyma (dysanaptic growth). Further studies in larger populations are needed to validate these observations.