Validating Four Hmong Word Recognition Tests With Normal-Hearing Bilingual Hmong Individuals.

PURPOSE: The purpose of this study was to validate four digitally recorded and phonetically balanced 50-word recognition lists in the White Hmong dialect with normal-hearing bilingual Hmong adults. METHOD: Using a randomized, incomplete-block design, each participant listened to and repeated four unique Hmong lists delivered by a female and a male talker. Participants were also tested with an English word list-List 1A of the Northwestern University Auditory Test No. 6. Participants' correct pronunciation of each word was scored. A nonparametric Mann-Whitney U Location Difference Test for Equivalence using two one-sided tests equivalence hypothesis: -0.02 < [(List_1) - (List_2)] < 0.02 was conducted to assess equivalence among all four Hmong and the English lists. RESULTS: Seventy Hmong speakers participated in this study (35 women, 35 men; M age = 29.5 years, SD = 7.1). In all four Hmong lists, 93.5% (187/200) words met the validation criteria for ≥ 92% correct pronunciation. The 13 difficult words were deemed adequate by a Hmong panel and, therefore, were included to maintain four unique, balanced word lists. The test revealed that the Hmong and English word lists were considered equivalent at the 2% bound. CONCLUSION: The four Hmong word lists were validated to ensure an equal range of word difficulty across the lists.

Cystic Ovarian Mucinous Carcinoma With Carcinosarcomatous Mural Nodules: An Uncommon Entity.

Mural nodules in ovarian mucinous cystic tumors are uncommon, with only 80 cases reported over the last 30 yr. The literature describes only 5 cases of carcinosarcomatous mural nodules with mucinous ovarian neoplasm. We compared and summarized the literature related to mural nodules in mucinous ovarian tumors to elaborate on the clinical and histomorphologic features. A 21-yr-old woman presented with 2 mo history of abdominal distension. Physical examination showed a palpable pelvic mass. Radiologic investigation showed a 31×18.6×25 cm large right ovarian cyst. Few nodular solid masses were also seen, the largest mass measured 3.5×3.1 cm. On histomorphology and immunohistochemistry, it was a mucinous ovarian carcinoma with carcinosarcomatous mural nodules. Carcinosarcomatous mural nodules with ovarian mucinous neoplasm affects younger females. It presents at an early stage and does not carry an adverse prognosis.

Papillary Endothelial Hyperplasia of Scalp with Bone Erosion: A Case Report with Review of Literature.

BACKGROUND: Papillary endothelial hyperplasia (PEH) is a reactive pseudoneoplastic proliferation of endothelial cells. They are typically well-circumscribed, indolent lesions and curable by complete excision. Description: We present a four-year-old girl with post traumatic scalp swelling, clinically considered to be a capillary hemangioma. Computed tomography revealed a 3.3 × 1.5 cm scalp mass with erosion of outer table and diploic space of the occipital calvarial bone, suggesting a vascular or soft tissue tumor. Histologically it was a PEH within a hemangioma. Literature Review: PEH presenting as a scalp swelling with bone erosion has only been reported thrice in the literature. Conclusion: Scalp PEH with skull bone defect can affect the pediatric age group. Bone erosion is not stage dependent; it can occur in the early stages.

Clinicopathological Study of 117 Body Fluids: Comparison of Conventional Smear and Cell Block Technique.

BACKGROUND: Cell block method (CB) has emerged as an invaluable tool for diagnosis of effusions. It can help overcome the problems faced by conventional smear (CS) by differentiating between reactive, inflammatory and malignant cells. The aim of the study is to compare and correlate the CB diagnosis with the CS findings of various pathological conditions including malignancy. MATERIALS AND METHODS: Two years prospective cross-sectional study of 117 fluids received for routine examination and/or for cytology was conducted. CS as well as CB was simultaneously prepared from the fluid and the results were correlated and tabulated for statistical analysis. RESULTS: Mean age of presentation was 43±21.1 years and male: female ratio was 1.3:1. Ascitic fluid (46.2%) was the most common followed by pleural (40.2%). Among malignancies, primary ovarian and lung carcinoma were the most common to present with malignant ascites (33.3%) and pleural effusion (66.7%) respectively. Six suspicious for malignancy on CS were provided a definitive diagnosis of malignancy on CB. Overall, CB increased the yield of malignancy by 8.3%. The agreement between CB and CS for malignant effusions and suspicious for malignancy were 41.7% and 14.3% respectively. Sensitivity of CS method when compared to CB, for malignant peritoneal and pleural effusions was 90% and 75% respectively while the specificity was 68% and 79% respectively. CONCLUSION: CB has a better diagnostic yield of malignancy and helps in providing a definitive diagnosis for cases that are suspicious for malignancy on CS. Hence, CB should be routinely employed along with CS for all effusions.

No Increased Mortality After TIPS Compared with Serial Large Volume Paracenteses in Patients with Higher Model for End-Stage Liver Disease Score and Refractory Ascites.

PURPOSE: To compare survival after transjugular intrahepatic portosystemic shunt (TIPS) creation versus serial large volume paracenteses (LVP) in patients with refractory ascites and higher Model for End-Stage Liver Disease (MELD) scores. MATERIALS AND METHODS: In this retrospective study, from 1/1/2013 to 10/1/2018, 478 patients (294 male; mean age 58, range 23-89) underwent serial LVP (n = 386) or TIPS (n = 92) for ascites. Propensity-matched cohorts were constructed based on age, MELD, Charlson comorbidity index, varices, and hepatic encephalopathy. Survival was analyzed using a Cox proportional hazards model in which MELD score and TIPS were treated as time-dependent covariates. An interaction term was used to assess the impact of TIPS versus serial LVP on survival as a function of increasing MELD. RESULTS: In the overall patient sample, higher MELD score predicted worse survival after either serial LVP or TIPS [hazard ratio (HR) = 1.13; p < 0.001], but there was no significant interaction between TIPS and higher MELD score conferring worse survival (HR = 1.01; p = 0.55). In 92 propensity-matched serial LVP and 92 TIPS patients, higher MELD score predicted worse survival after either serial LVP or TIPS (HR = 1.19; p < 0.001), but there was no significant survival interaction between TIPS and higher MELD (HR = 0.97; p = 0.22). In 30 propensity-matched serial LVP patients and 30 TIPS patients with baseline MELD greater than 18, TIPS did not predict worse survival (HR = 0.97; p = 0.94). CONCLUSION: Higher MELD predicts poorer survival after either serial LVP or TIPS, but TIPS creation is not associated with worse survival compared to serial LVP in patients with higher MELD scores LEVEL OF EVIDENCE: Level 4, case series.

Sonographic Evaluation of Clinically Significant Perigraft Hematomas in Kidney Transplant Recipients.

OBJECTIVE: The purpose of this study was to assess the sensitivity of ultrasound in evaluating peritransplant hematomas that require surgical evacuation in recipients of kidney transplants. MATERIALS AND METHODS: Thirty-four patients who underwent 37 hematoma evacuations underwent ultrasound examinations in the 24 hours before surgical evacuation. The operative reports were evaluated for presence and size of collection, presence of active bleeding at operation, and composition of the hematoma. The clinical findings leading to the ultrasound examination were recorded. Ultrasound examinations were evaluated in consensus by two board-certified and fellowship-trained abdominal radiologists for the presence, size, and echogenicity of the collection; subjective perfusion visualized with color and power Doppler ultrasound; velocities of the renal arteries; and arcuate artery resistive indexes. RESULTS: Ten of the 37 imaged hematomas (27%) had either no or small (< 50 mL) fluid collections on ultrasound examination. With sonographic volumetry, the reported intraoperative volumes were underestimated by 46%. The mean arcuate artery resistive index was 0.82 in the superior pole, 0.81 in the mid pole, and 0.78 in the inferior pole of the kidney. A decrease in hemoglobin level was the most sensitive clinical finding for determining the presence of perigraft hematomas. CONCLUSION: Our results suggest that gray-scale sonography alone appears to have limited sensitivity in detecting clinically significant peritransplant hematomas and that its use may result in overall underestimates of hematomas.

Epithelial membrane protein-2 (EMP2) activates Src protein and is a novel therapeutic target for glioblastoma.

Despite recent advances in molecular classification, surgery, radiotherapy, and targeted therapies, the clinical outcome of patients with malignant brain tumors remains extremely poor. In this study, we have identified the tetraspan protein epithelial membrane protein-2 (EMP2) as a potential target for glioblastoma (GBM) killing. EMP2 had low or undetectable expression in normal brain but was highly expressed in GBM as 95% of patients showed some expression of the protein. In GBM cells, EMP2 enhanced tumor growth in vivo in part by up-regulating αvß3 integrin surface expression, activating focal adhesion kinase and Src kinases, and promoting cell migration and invasion. Consistent with these findings, EMP2 expression significantly correlated with activated Src kinase in patient samples and promoted tumor cell invasion using intracranial mouse models. As a proof of principle to determine whether EMP2 could serve as a target for therapy, cells were treated using specific anti-EMP2 antibody reagents. These reagents were effective in killing GBM cells in vitro and in reducing tumor load in subcutaneous mouse models. These results support the role of EMP2 in the pathogenesis of GBM and suggest that anti-EMP2 treatment may be a novel therapeutic treatment.

Measuring cardiac index with a focused cardiac ultrasound examination in the ED.

OBJECTIVES: Noninvasive technology may assist the emergency department (ED) physician in determining the hemodynamic status in critically ill patients. The objective of our study was to show that ED physicians can accurately measure cardiac index (CI) by performing a bedside focused cardiac ultrasound examination. METHODS: A convenience sample of adult subjects were prospectively enrolled. Cardiac index, left ventricular outflow tract (LVOT) diameter, velocity time integral (VTI), stroke volume index, and heart rate were obtained by trained ED physicians and a certified cardiac sonographer. The primary outcome was percent of optimal LVOT diameter and VTI measurements as verified by an expert cardiologist. RESULTS: One hundred patients were enrolled, with obtainable CI measurements in 97 patients. Cardiac index, LVOT diameter, VTI, stroke volume index, and heart rate measurements by ED physician were 2.42 ± 0.70 L min(-1) m(-2), 2.07 ± 0.22 cm, 18.30 ± 3.71 cm, 32.34 ± 7.92 mL beat(-1) m(-2), and 75.32 ± 13.45 beats/min, respectively. Measurements of LVOT diameter by ED physicians and sonographer were optimal in 90.0% (95% confidence interval, 82.6%-94.5) and 91.3% (73.2%-97.6%) of patients, respectively. Optimal VTI measurements were obtained in 78.4% (69.2%-85.4%) and 78.3% (58.1%-90.3%) of patients, respectively. In 23 patients, the correlation (r) for CI between ED physician and sonographer was 0.82 (0.60-0.92), with bias and limits of agreement of -0.11 (-1.06 to 0.83) L min(-1) m(-2) and percent difference of 12.4% ± 10.1%. CONCLUSIONS: Emergency department ED physicians can accurately measure CI using standard bedside ultrasound. A focused ultrasound cardiac examination to derive CI has potential use in the management of critical ill patients in the ED.

Epithelial membrane protein-2 promotes endometrial tumor formation through activation of FAK and Src.

Endometrial cancer is the most common gynecologic malignancy diagnosed among women in developed countries. One recent biomarker strongly associated with disease progression and survival is epithelial membrane protein-2 (EMP2), a tetraspan protein known to associate with and modify surface expression of certain integrin isoforms. In this study, we show using a xenograft model system that EMP2 expression is necessary for efficient endometrial tumor formation, and we have started to characterize the mechanism by which EMP2 contributes to this malignant phenotype. In endometrial cancer cells, the focal adhesion kinase (FAK)/Src pathway appears to regulate migration as measured through wound healing assays. Manipulation of EMP2 levels in endometrial cancer cells regulates the phosphorylation of FAK and Src, and promotes their distribution into lipid raft domains. Notably, cells with low levels of EMP2 fail to migrate and poorly form tumors in vivo. These findings reveal the pivotal role of EMP2 in endometrial cancer carcinogenesis, and suggest that the association of elevated EMP2 levels with endometrial cancer prognosis may be causally linked to its effect on integrin-mediated signaling.

Peripheral myelin protein-22 (PMP22) modulates alpha 6 integrin expression in the human endometrium.

BACKGROUND: PMP22, a member of the GAS3 family of tetraspan proteins, is associated with a variety of neurological diseases. Previous studies have shown that PMP22 is expressed in proliferative endometrium, but its function within this tissue is poorly understood. In this study, we first characterized the expression of PMP22 in the human menstrual cycle and began to characterize its function in the endometrium. METHODS: Using a combination of immunohistochemistry and quantitative PCR, we characterized the expression of PMP22 in both proliferative and secretory endometrium. Differences in PMP22 expression between proliferative and secretory endometrium were determined using a Mann-Whitney U test. In order to investigate the influence of PMP22 on α6 integrin expression, cells were created that ectopically overexpressed PMP22 or expressed a siRNA to inhibit its expression. These cells were analyzed for changes in integrins and binding to extracellular matrices. RESULTS: In this study, we show that PMP22 expression is higher in proliferative phase than secretory phase. Functionally, we have begun to characterize the functional significance of this expression. Previous studies have suggested a link between PMP22 and α6 integrin, and therefore we asked whether PMP22 could associate or potentially modulate the expression of α6 integrin. Expression of both PMP22 and α6 integrin were detectable in endometrial epithelial and stromal cells, and we show that both proteins can associate and colocalize with each other. To understand if PMP22 directly altered the expression of a6 integrin, we examined cell lines with modulated levels of the protein. Overexpression of PMP22 was sufficient to increase α6 integrin surface expression with a concominant increase in binding to the extracellular matrix laminin, while a reduction in PMP22 suppressed α6 integrin surface expression. CONCLUSION: These findings suggest a physiologic role for PMP22 on the expression of α6 integrin. We predict that this may be important for the maintainence of endometrial integrity and to the disease biology associated with altered levels of α6 integrin expression in the endometrium.

Epithelial membrane protein-2 expression is an early predictor of endometrial cancer development.

BACKGROUND: Endometrial cancer (EC) is a common malignancy worldwide. It is often preceded by endometrial hyperplasia, whose management and risk of neoplastic progression vary. Previously, the authors have shown that the tetraspan protein epithelial membrane protein-2 (EMP2) is a prognostic indicator for EC aggressiveness and survival. Here the authors validate the expression of EMP2 in EC, and further examine whether EMP2 expression within preneoplastic lesions is an early prognostic biomarker for EC development. METHODS: A tissue microarray (TMA) was constructed with a wide representation of benign and malignant endometrial samples. The TMA contains a metachronous cohort of cases from individuals who either developed or did not develop EC. Intensity and frequency of EMP2 expression were assessed using immunohistochemistry. RESULTS: There was a stepwise, statistically significant increase in the average EMP2 expression from benign to hyperplasia to atypia to EC. Furthermore, detailed analysis of EMP2 expression in potentially premalignant cases demonstrated that EMP2 positivity was a strong predictor for EC development. CONCLUSIONS: EMP2 is an early predictor of EC development in preneoplastic lesions. In addition, combined with our previous findings, these results validate EMP2 as a novel biomarker for EC development.

Steroid hormone regulation of EMP2 expression and localization in the endometrium.

BACKGROUND: The tetraspan protein epithelial membrane protein-2 (EMP2), which mediates surface display of diverse proteins, is required for endometrial competence in blastocyst implantation, and is uniquely correlated with poor survival from endometrial adenocarcinoma tumors. Because EMP2 is differentially expressed in the various stages of the murine and human estrous cycle, we tested the hypothesis that the steroid hormones progesterone and estrogen influence EMP2 expression and localization. METHODS: Frozen human proliferative and secretory endometrium were collected and analyzed for EMP2 expression using SDS-PAGE/Western blot analysis. The response of EMP2 to progesterone and estradiol was determined using a combination of real-time PCR, SDS-PAGE/Western blot analysis, and confocal immunofluorescence in the human endometrial carcinoma cell line RL95-2. To confirm the in vitro results, ovariectomized mice were treated with progesterone or estradiol, and EMP2 expression was analyzed using immunohistochemistry. RESULTS: Within normal human endometrium, EMP2 expression is upregulated in the secretory phase relative to the proliferative phase. To understand the role of steroid hormones on EMP2 expression, we utilized RL95-2 cells, which express both estrogen and progesterone receptors. In RL95-2 cells, both estradiol and progesterone induced EMP2 mRNA expression, but only progesterone induced EMP2 protein expression. To compare steroid hormone regulation of EMP2 between humans and mice, we analyzed EMP2 expression in ovarectomized mice. Similar to results observed in humans, progesterone upregulated endometrial EMP2 expression and induced EMP2 translocation to the plasma membrane. Estradiol did not promote translocation to the cell surface, but moderately induced EMP2 expression in cytoplasmic compartments in vivo. CONCLUSION: These findings suggest that targeting of EMP2 to specific locations under the influence of these steroid hormones may be important for integrating the molecular responses required for implantation competence.