FcRn in the yolk sac endoderm of mouse is required for IgG transport to fetus.

In adults, the nonclassical MHC class I molecule, FcRn, binds both IgG and albumin and rescues both from a degradative fate, endowing both proteins with high plasma concentrations. FcRn also transports IgG from mother to young during gestation. Anticipating that a detailed understanding of gestational IgG transport in the mouse may give us a useful model to understand FcRn function in the human placenta, we have studied FcRn in the mouse yolk sac placenta in detail. Analyzing day 19-20 fetuses of the three FcRn genotypes resulting from matings of FcRn(+/-) parents, we found that FcRn(-/-) fetuses showed negligible IgG concentrations (1.5 microg/ml), whereas IgG concentrations in FcRn(+/-) fetuses were about a half (176 microg/ml) that of FcRn(+/+) fetuses (336 microg/ml), indicating that FcRn is responsible for virtually all IgG transport from mother to fetus. Immunofluorescence and immunoblotting studies indicated that FcRn is expressed in the endoderm of the yolk sac placenta but not in other cells of the yolk sac placenta or in the chorioallantoic placenta. IgG was found in the endoderm of both FcRn(+/+) and FcRn(-/-) yolk sac placentas and in the mesenchyme of FcRn(+/+) but was missing from the mesenchyme of FcRn(-/-) yolk sac placentas, indicating that IgG enters the endoderm constitutively but is moved out of the endoderm by FcRn. The similarities of these results to human placental FcRn expression and function are striking.

A randomized trial testing the superiority of a postdischarge care management model for stroke survivors.

OBJECTIVE: We sought to evaluate whether comprehensive postdischarge care management for stroke survivors is superior to organized acute stroke department care with enhanced discharge planning in improving a profile of health and well-being. METHODS: This was a randomized trial of a comprehensive postdischarge care management intervention for patients with ischemic stroke and National Institutes of Health Stroke Scale scores greater than or equal to 1 discharged from an acute stroke department. An advanced practice nurse performed an in-home assessment for the intervention group from which an interdisciplinary team developed patient-specific care plans. The advanced practice nurse worked with the primary care physician and patient to implement the plan during the next 6 months. The intervention and usual care groups were compared using a global and closed hypothesis testing strategy. Outcomes fell into 5 domains: (1) neuromotor function, (2) institution time or death, (3) quality of life, (4) management of risk, and (5) stroke knowledge and lifestyle. RESULTS: Treatment effect was near 0 SD for all except the stroke knowledge and lifestyle domain, which showed a significant effect of the intervention (P = .0003). CONCLUSIONS: Postdischarge care management was not more effective than organized stroke department care with enhanced discharge planning in most domains in this population. The intervention did, however, fill a postdischarge knowledge gap.

The after discharge care management of low income frail elderly (AD-LIFE) randomized trial: theoretical framework and study design.

Interdisciplinary care management is advocated for optimal care of patients with many types of chronic illnesses; however, few models exist that have been tested using randomized trials. The purpose of this report is to describe the theoretical basis for the After Discharge Management of Low Income Frail Elderly (AD-LIFE) trial, which is an ongoing 2-group randomized trial (total n = 530) to test a chronic illness management and transitional care intervention. The intervention is based on Wagner's chronic illness care model and involves comprehensive posthospitalization nurse-led interdisciplinary care management for low income frail elders with chronic illnesses, employs evidence-based protocols that were developed using the Assessing Care of Vulnerable Elders (ACOVE) guidelines, emphasizes patient activation, and integrates with community-based long-term care and other community agencies. The primary aim of the AD-LIFE trial is to test a chronic illness management intervention in vulnerable patients who are eligible for Medicare and Medicaid. This model, with its standardized, evidence-based medical and psychosocial intervention protocols, will be easily transportable to other sites interested in optimizing outcomes for chronically ill older adults. If the results of the AD-LIFE trial demonstrate the superiority of the intervention, then this data will be important for health care policy makers.

The relationship between body mass index and thyroid cancer pathology features and outcomes: a clinicopathological cohort study.

BACKGROUND: Obesity has been implicated as a predisposing and disease-modifying factor in cancer. Epidemiological studies suggest that obesity is associated with an increased risk of thyroid cancer; however, the relationships between obesity and thyroid cancer stage or behavior are uncertain. We hypothesized that a higher body mass index (BMI) would be associated with aggressive thyroid cancer features and a higher incidence of persistent/recurrent disease. METHODS: Two hundred fifty-nine consecutive patients with thyroid cancer were enrolled in this retrospective cohort study. Histopathological tumor features, stage at diagnosis, and disease status during and at the end of the study were determined based on chart review. BMI was calculated at the first clinical visit to our institution. The relationships between BMI and these parameters were assessed. RESULTS: Mean follow-up time for the group was 6.2 yr (0.11-46 yr). No positive associations were identified between BMI and T, N, or M stage at diagnosis, vascular invasion, or recurrent or persistent disease on univariate or multivariate analyses. The absence of an association was also demonstrated on analysis by BMI quartiles. An unexpected inverse association was identified between BMI and nodal metastasis and tumor invasion on both univariate and multivariate analyses, suggesting that obesity may be associated with less aggressive tumor features, a finding that requires confirmatory studies. CONCLUSION: Although obesity has been associated with increased thyroid cancer incidence, a higher BMI was found not to be associated with more aggressive tumor features or a greater likelihood of recurrence or persistence over the analyzed time period.

Piwil2 expressed in various stages of cervical neoplasia is a potential complementary marker for p16.

Generally, cancers may undergo the developmental stages of benign proliferation, precancer and invasive cancer. Identification of biomarkers that are expressed throughout the developmental stages will facilitate detection, prevention and therapy of cancer. Piwil2, a member of AGO/PIWI family of proteins, has been suggested to be associated with tumor development. Here we reported that piwil2 can be detected by immunohistochemistry (IHC) in various stages of human cervical squamous cell carcinomas and adenocarcinomas. Interestingly, piwil2 was also detected in some metaplastic epithelial cells as well as histologically "normal" appearing tissues adjacent to malignant lesions. While all the premalignant and malignant lesions expressed varying levels of piwil2, p16(INK4a) (p16), a surrogate indicator of high-risk human papillomavirus (HR-HPV) infection, was detected in only 84.62% of the specimens. In Papanicolaou (Pap) test, piwil2 was also detected in atypical glandular cells (AGC), low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL), whereas p16 was not always concomitantly detected in the same specimens. The results suggest that piwil2 might play important roles throughout the process of cervical cancer development and have the potential to be used as a complementary marker for p16(INK4a). It is worth further study to improve the sensitivity and specificity of current screening methods for cervical cancers.

IgG is transported across the mouse yolk sac independently of FcgammaRIIb.

While generally accepted that FcRn of the human syncytiotrophoblast and the mouse yolk sac endoderm is the major IgG transporter, the finding of a different Fc receptor FcgammaRIIb (RIIb) in the human placental endothelium has suggested the existence of an additional IgG transporter. Testing our hypothesis in mouse, we found that while RIIb is expressed in the yolk sac vasculature, IgG concentrations in fetuses of wild-type mice (RIIb(+/+)) and mice with a null mutation in the gene encoding RIIb (RIIb(-/-) mice) are not different, and we thus reject our hypothesis that yolk sac RIIb transports IgG in utero in the mouse. However, the capillary bed in the mouse yolk sac is structurally more complex than in human placenta, consisting of three types of cells: an RIIb-negative endothelium, a unique RIIb-bearing cell that also expresses 2 out of 4 macrophage markers but not endothelial cell or pericyte markers, and pericytes. As in the human placenta the b2 isoform of RIIb predominates in the mouse yolk sac. Remarkably only a single capillary channel rather than 2 channels with a loop is found in each yolk sac villus, which, along with intracapillary erythrocytes, suggests that blood flow is peristaltic, mediated by pericytes. It is not clear whether RIIb in the human placental villus might mediate an IgG transport function in light of the mouse yolk sac equivalent failing to do so.

Piwil2 is expressed in various stages of breast cancers and has the potential to be used as a novel biomarker.

Piwil2, a member of AGO/PIWI family of proteins, has been reported to be expressed in precancerous stem cells (pCSCs), tumor cell lines and various types of human cancers. However, the significance of piwil2 expression in breast cancer has not been investigated. In this study, archival formalin-fixed, paraffin-embedded breast cancer specimens at various developmental stages were prepared as tissue microarrays (TMAs) and examined for the expressions of piwil2, estrogen receptor (ER), progesterone receptor (PR) and a cell proliferation marker Ki67 by immunohistochemical (IHC) staining and human epidermal growth factor receptor 2 (HER2) by fluorescence in situ hybridization (FISH). The correlation of piwil2 expression with ER, PR and Ki67 were analyzed statistically. The piwil2 was detected in all of breast cancer TMA cores. In contrast, ER, PR, HER2, and Ki67 were detected only in 66.1%, 54.5%, 36.0%, and 47% of the TMA cores, respectively. Piwil2 was expressed in cytoplasm (Cyt), nucleus (N) or both cytoplasm and nucleus (C-N). The N pattern was less observed in breast precancers, whereas all three patterns were observed in invasive and metastatic cancers. While the Cyt pattern was significantly correlated with ER expression (p = 0.002); N pattern was significantly correlated with Ki67 expression (p =0.001). ER and Ki67 expressions were reduced and increased, respectively, with the expression patterns being shifted from Cyt --> C-N --> N. In conclusion, piwil2 is expressed in various stages of breast cancers and has the potential to be used a novel biomarker.

Cardiac effects of continuous and bilevel positive airway pressure for patients with heart failure and obstructive sleep apnea: a pilot study.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in patients with heart failure. Treatment with continuous positive airway pressure (CPAP) improves systolic function in patients with heart failure. Bilevel positive airway pressure (PAP) is another treatment modality for OSA. The intermediate-term effect of bilevel PAP on left ventricular ejection fraction (LVEF) in patients with stable heart failure and OSA has not been compared to the effect of CPAP. METHODS: In this pilot randomized controlled trial, patients with stable systolic dysfunction and newly diagnosed OSA (n = 24) were randomized to receive either CPAP or bilevel PAP. Titration was done in the sleep laboratory using a CPAP-based algorithm. Primary outcome was the improvement in LVEF after 3 months of treatment. Other measurements included 6-min walk test, Epworth sleepiness scale score, and the Minnesota Living With Heart Failure questionnaire. RESULTS: Bilevel PAP increased LVEF 7.9% (LVEF percentage scale) more than CPAP (95% confidence interval [CI], 2.3 to 13.4; p = 0.01). In the bilevel PAP group, LVEF increased 8.5% (95% CI, 3.7 to 13.4; p = 0.002). In the CPAP group, LVEF did not change significantly (0.5%; 95% CI, - 2.7 to 3.7; p = 0.7). The difference in LVEF improvement between the two groups was still significant after adjustment for adherence, level of treatment positive pressure, body mass index, and severity of OSA. CONCLUSION: This pilot randomized controlled trial suggests that bilevel PAP is superior to CPAP in improving LVEF in patients with systolic dysfunction and OSA. Larger trials are required to evaluate the mechanism behind this effect.

A pilot study: post-acute geriatric rehabilitation versus usual care in skilled nursing facilities.

OBJECTIVES: To compare discharge outcomes, postdischarge health care use, and death rates among patients treated in a postacute geriatric rehabilitation unit (GRU) housed within a skilled nursing facility (SNF) with those treated in a traditional SNF. DESIGN: Retrospective observational pilot study. SETTING: Two similar SNFs were compared. PARTICIPANTS: All patients were admitted from the acute hospital to either the GRU (n = 95) or to the usual care (UC) SNF (n = 55). INTERVENTION: The GRU intervention consisted of comprehensive geriatric assessment and weekly interdisciplinary team rounds with a geriatrician and a geriatric nurse practitioner (GNP). The geriatrician visited the GRU twice a week and the GNP was present 4 to 5 times per week. On discharge, GRU patients were followed up with telephonic case management for 1 year. MEASUREMENTS: Demographic data collected included age, gender, and race. Information collected from each facility's patient records included admitting diagnosis, length of stay, discharge disposition, and functional outcomes. Emergency department (ED) visits and hospital readmissions for 1 year after discharge from the nursing facility were obtained from our institutional database. The Rehabilitation Outcome Measure (ROM) was used by each facility to measure functional status on admission and at the time of discharge. RESULTS: Baseline patient characteristics were comparable between the 2 facilities. At discharge from the nursing facility, GRU patients showed greater improvement in ADLs and mobility, had a significantly shorter length of stay, and were discharged to home more often. At 1 year, GRU patients had significantly fewer hospital readmissions. GRU patients also had fewer ED visits and days in the hospital at 1 year, however these results were not significant. CONCLUSION: These pilot results suggest that GRU may be an effective means to improve patient outcomes and reduce undesirable health care use after an acute illness. Further studies using a randomized design are needed.