Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection.

In response to acute infection, naive CD4+ T cells primarily differentiate into T helper 1 (Th1) or T follicular helper (Tfh) cells that play critical roles in orchestrating cellular or humoral arms of immunity, respectively. However, despite the well established role of T-bet and BCL-6 in driving Th1 and Tfh cell lineage commitment, respectively, whether additional transcriptional circuits also underlie the fate bifurcation of Th1 and Tfh cell subsets is not fully understood. In this article, we study how the transcriptional regulator Bhlhe40 dictates the Th1/Tfh differentiation axis in mice. CD4+ T cell-specific deletion of Bhlhe40 abrogates Th1 but augments Tfh differentiation. We also assessed an increase in germinal center B cells and Ab production, suggesting that deletion of Bhlhe40 in CD4+ T cells not only alters Tfh differentiation but also their capacity to provide help to B cells. To identify molecular mechanisms by which Bhlhe40 regulates Th1 versus Tfh lineage choice, we first performed epigenetic profiling in the virus specific Th1 and Tfh cells following LCMV infection, which revealed distinct promoter and enhancer activities between the two helper cell lineages. Furthermore, we identified that Bhlhe40 directly binds to cis-regulatory elements of Th1-related genes such as Tbx21 and Cxcr6 to activate their expression while simultaneously binding to regions of Tfh-related genes such as Bcl6 and Cxcr5 to repress their expression. Collectively, our data suggest that Bhlhe40 functions as a transcription activator to promote Th1 cell differentiation and a transcription repressor to suppress Tfh cell differentiation.

Inflammatory heterogeneity in aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is a mechanistically distinct subtype of chronic rhinosinusitis with nasal polyps (CRSwNP). Although frequently associated with type 2 inflammation, literature characterizing the milieu of inflammatory cytokines and lipid mediators in AERD has been conflicting. OBJECTIVE: We sought to identify differences in the upper airway inflammatory signature between CRSwNP and AERD and determine whether endotypic subtypes of AERD may exist. METHODS: Levels of 7 cytokines representative of type 1, type 2, and type 3 inflammation, and 21 lipid mediators were measured in nasal mucus from 109 patients with CRSwNP, 30 patients with AERD, and 64 non-CRS controls. Differences in inflammatory mediators were identified between groups, and patterns of inflammation among patients with AERD were determined by hierarchical cluster analysis. RESULTS: AERD could be distinguished from CRSwNP by profound elevations in IL-5, IL-6, IL-13, and IFN-γ; however, significant heterogeneity existed between patients. Hierarchical cluster analysis identified 3 inflammatory subendotypes of AERD characterized by (1) low inflammatory burden, (2) high type 2 cytokines, and (3) comparatively low type 2 cytokines and high levels of type 1 and type 3 cytokines. Several lipid mediators were associated with asthma and sinonasal disease severity; however, lipid mediators showed less variability than cytokines. CONCLUSIONS: AERD is associated with elevations in type 2 cytokines (IL-5 and IL-13) and the type 1 cytokine, IFN-γ. Among patients with AERD, the inflammatory signature is heterogeneous, supporting subendotypes of the disease. Variability in AERD immune signatures should be further clarified because this may predict clinical response to biologic medications that target type 2 inflammation.

Airway Management and Clinical Outcomes in External Laryngeal Trauma: A Case Series.

External laryngeal trauma is a rare but potentially fatal event that presents several management challenges. This retrospective observational case series conducted at a level-1 trauma center over a 12-year period consists of 62 cases of acute external laryngeal trauma. Patient demographics, mode and mechanisms of injury, presenting signs and symptoms, initial imaging results, airway management, time to surgical management, and 6-month outcomes including airway status, deglutition status, and voice quality were investigated. No difference was found in mortality or 6-month outcomes between patients requiring surgical repair and/or tracheostomy versus patients with less severe injuries managed conservatively.

Differential effects of complement activation products c3a and c5a on cardiovascular function in hypertensive pregnant rats.

Early-onset pre-eclampsia is characterized by decreased placental perfusion, new-onset hypertension, angiogenic imbalance, and endothelial dysfunction associated with excessive activation of the innate immune complement system. Although our previous studies demonstrated that inhibition of complement activation attenuates placental ischemia-induced hypertension using the rat reduced uterine perfusion pressure (RUPP) model, the important product(s) of complement activation has yet to be identified. We hypothesized that antagonism of receptors for complement activation products C3a and C5a would improve vascular function and attenuate RUPP hypertension. On gestational day (GD) 14, rats underwent sham surgery or vascular clip placement on ovarian arteries and abdominal aorta (RUPP). Rats were treated once daily with the C5a receptor antagonist (C5aRA), PMX51 (acetyl-F-[Orn-P-(D-Cha)-WR]), the C3a receptor antagonist (C3aRA), SB290157 (N(2)-[(2,2-diphenylethoxy)acetyl]-l-arginine), or vehicle from GD 14-18. Both the C3aRA and C5aRA attenuated placental ischemia-induced hypertension without affecting the decreased fetal weight or decreased concentration of free circulating vascular endothelial growth factor (VEGF) also present in this model. The C5aRA, but not the C3aRA, attenuated placental ischemia-induced increase in heart rate and impaired endothelial-dependent relaxation. The C3aRA abrogated the acute pressor response to C3a peptide injection, but it also unexpectedly attenuated the placental ischemia-induced increase in C3a, suggesting nonreceptor-mediated effects. Overall, these results indicate that both C3a and C5a are important products of complement activation that mediate the hypertension regardless of the reduction in free plasma VEGF. The mechanism by which C3a contributes to placental ischemia-induced hypertension appears to be distinct from that of C5a, and management of pregnancy-induced hypertension is likely to require a broad anti-inflammatory approach.

AICAR administration ameliorates hypertension and angiogenic imbalance in a model of preeclampsia in the rat.

Previous studies suggest restoration of angiogenic balance can lower blood pressure and improve vascular endothelium function in models of preeclampsia. Our laboratory has recently reported exercise training mitigates hypertension in an animal model of preeclampsia, but the mechanisms are unknown. AMP-activated protein kinase (AMPK) is stimulated during exercise and has been shown to increase expression of VEGF. Therefore, the purpose of this study was to determine whether AICAR (5-aminoimidazole-4-carboxamide-3-ribonucleoside), a potent AMPK stimulator, would increase circulating VEGF, improve angiogenic potential, decrease oxidative stress, and abrogate placental ischemia-induced hypertension. In rats, reduced uteroplacental perfusion pressure (RUPP) was induced on day 14 of gestation by introducing silver clips on the inferior abdominal aorta and ovarian arteries. AICAR was administered intraperitoneally (50 mg/kg b.i.d.) days 14-18, and blood pressure and tissues were collected on day 19. RUPP-induced hypertension was ameliorated (P < 0.05) with AICAR versus RUPP. AICAR increased (P < 0.05) plasma VEGF and decreased (P < 0.05) plasma soluble VEGF receptor-1 in the RUPP + AICAR versus RUPP. Antioxidant capacity was restored (P < 0.05) by AICAR in RUPP placenta. Renal and placental catalase activity was decreased (P < 0.05) in RUPP + AICAR versus RUPP. Angiogenic potential was increased (P < 0.05) in RUPP + AICAR versus RUPP. Fetal and placental weights were unaffected by AICAR. Placental AMPK phosphorylation was increased (P < 0.05) in RUPP + AICAR versus normal pregnant and RUPP. These findings suggest AICAR may be useful to mitigate angiogenic imbalance, renal, and placental oxidative stress and increase in blood pressure associated with RUPP hypertension. Furthermore, placental AMPK phosphorylation was observed only in the setting of ischemia.

Bilateral Longus Colli Abscesses as a Complication of Advanced Bacterial Rhinosinusitis.

Known complications of acute bacterial rhinosinusitis include retropharyngeal abscess, cavernous sinus thrombosis, intracranial abscess, and associated sequelae. We describe the case of a patient with longus colli abscess formation resulting from acute pansinusitis, complicated by bilateral cavernous sinus thrombosis in the setting of concurrent viral pneumonitis, severe sepsis, and a large area cerebral infarction. The bilateral longus colli abscesses were drained via stereotactic image-guided endonasal sinus surgery, yielding Staphylococcus hominis in culture. The described disease progressed rapidly over a 2-week course amid the COVID-19 pandemic.

Balloon Sinuplasty and Stenting in the Management of Complex Frontal Sinus Outflow Tract Fractures.

OBJECTIVE: Classical management of complex fractures involving the frontal sinus outflow tract (FSOT) favors obliteration or cranialization to avoid delayed complications. We aim to exhibit success with a novel application of balloon sinuplasty and frontal stenting in the management of complex injuries disrupting the FSOT, which might have otherwise required more invasive interventions. STUDY DESIGN: Retrospective review. SETTING: Single institution, level 1 trauma center. METHODS: Retrospective review of patients presenting to a level 1 trauma center with fractures involving the FSOT. Outcomes include patency of the FSOT on imaging and endoscopy, rate of complications, degree of residual tabular displacement, and need for revision surgery. RESULTS: Twenty-five patients met inclusion criteria, with complete FSOT obstruction seen in all cases on computed tomography. All patients underwent balloon sinuplasty with frontal sinus stenting; 48% underwent concurrent anterior table repair, and 36% open repair of nasoorbitoethmoid complex fractures. The mean follow-up length was 13.9 months, at which time 91.3% of patients demonstrated radiographic and endoscopic FSOT patency. No residual sinus opacification or pneumocephalus was observed. CONCLUSION: Balloon sinuplasty with frontal sinus stenting is a straightforward and minimally invasive technique that can create a safe sinus in complex fractures disrupting the FSOT while avoiding the need for more invasive procedures.

Timing of ischemic insult alters fetal growth trajectory, maternal angiogenic balance, and markers of renal oxidative stress in the pregnant rat.

Increased uterine artery resistance and angiogenic imbalance characterized by increased soluble fms-like tyrosine kinase-1 (sFlt-1) and decreased free vascular endothelial growth factor (VEGF) are often associated with placental insufficiency and preeclampsia but not synonymous with hypertension. We hypothesized chronic reductions in utero-placental perfusion (RUPP) for 5 days (d) during either mid- (d12-d17) or late (d14-d19) gestation would have disparate effects on plasma sFlt-1 and VEGF levels and blood pressure. Five days of chronic RUPP was achieved by placement of silver clips on the abdominal aorta and ovarian arteries on either gestational d12 or d14. Arterial pressure was increased (P < 0.05) in RUPP vs. normal pregnant (NP) in both d17 (10%) and d19 (25%) groups, respectively. Circulating free VEGF was decreased (P < 0.05) and sFlt-1:VEGF ratio increased (P < 0.05) after 5 days of RUPP ending on d19 but not d17 compared with NP controls. Angiogenic imbalance, measured by an endothelial tube formation assay, was present in the d19 RUPP but not the d17 RUPP compared with age-matched NP rats. Five days of RUPP from days 14 to 19 decreased fetal and placental weights 10% (P < 0.01) compared with d19 NP controls. After 5 days of RUPP, from days 12 to 17 of pregnancy, fetal weights were 21% lighter (P < 0.01) compared with d17 NP controls, but placental weight was unchanged. These findings suggest that the timing during which placental insufficiency occurs may play an important role in determining the extent of alterations in angiogenic balance, fetal growth restriction, and the severity of placental ischemia-induced hypertension.

Placental and vascular adaptations to exercise training before and during pregnancy in the rat.

Although exercise during pregnancy is generally recommended and thought to be beneficial to mother and fetus, the nature of the adaptations to exercise during pregnancy and how they may be beneficial remain poorly understood. Recent studies suggest that exercise may stimulate expression of several cytoprotective and pro-angiogenic molecules such as heat shock proteins (HSP) and vascular endothelial growth factors (VEGF). We hypothesized that exercise training during pregnancy improves angiogenic balance, increases HSP expression, and improves endothelial function. Female rats were given access to an exercise wheel for 6 wk before and during pregnancy. On day 19 of pregnancy tissues were collected and snap frozen for later analysis. Western blots were performed in skeletal muscle and placenta. HSP 27 (3.7 ± 0.36 vs. 2.2 ± 0.38; P < 0.05), HSP 60 (2.2 ± 0.73 vs. 0.49 ± 0.08; P < 0.05), and HSP 90 (0.33 ± 0.09 vs. 0.11 ± 0.02; P < 0.05) were increased in the placentas of exercise-trained rats compared with sedentary controls. In addition, exercise training increased (P < 0.05) plasma free VEGF and augmented (P < 0.05) endothelium-dependent vascular relaxation compared with nonexercise control rats. The present data indicates chronic exercise training stimulates HSP expression in the placenta and that regular exercise training increases circulating VEGF in pregnant but not in nonpregnant rats. Although the present findings suggest that exercise before and during pregnancy may promote the expression of molecules that could attenuate placental and vascular dysfunction in complicated pregnancies, further studies are needed to determine the safety and effectiveness of exercise training as a therapeutic modality in pregnancy.

Toll-like receptor 2 regulates organic dust-induced airway inflammation.

Organic dust exposure in agricultural environments results in significant airway inflammatory diseases. Gram-positive cell wall components are present in high concentrations in animal farming dusts, but their role in mediating dust-induced airway inflammation is not clear. This study investigated the role of Toll-like receptor (TLR) 2, a pattern recognition receptor for gram-positive cell wall products, in regulating swine facility organic dust extract (DE)-induced airway inflammation in mice. Isolated lung macrophages from TLR2 knockout mice demonstrated reduced TNF-α, IL-6, keratinocyte chemoattractant/CXCL1, but not macrophage inflammatory protein-2/CXCL2 expression, after DE stimulation ex vivo. Next, using an established mouse model of intranasal inhalation challenge, we analyzed bronchoalveolar lavage fluid and lung tissue in TLR2-deficient and wild-type (WT) mice after single and repetitive DE challenge. Neutrophil influx and select cytokines/chemokines were significantly lower in TLR2-deficient mice at 5 and 24 hours after single DE challenge. After daily exposure to DE for 2 weeks, there were significant reductions in total cellularity, neutrophil influx, and TNF-α, IL-6, CXCL1, but not CXCL2 expression, in TLR2-deficient mice as compared with WT animals. Lung pathology revealed that bronchiolar inflammation, but not alveolar inflammation, was reduced in TLR2-deficient mice after repetitive exposure. Airway hyperresponsiveness to methacholine after dust exposure was similar in both groups. Finally, airway inflammatory responses in WT mice after challenge with a TLR2 agonist, peptidoglycan, resembled DE-induced responses. Collectively, these results demonstrate that the TLR2 pathway is important in regulating swine facility organic dust-induced airway inflammation, which suggests the importance of TLR2 agonists in mediating large animal farming-induced airway inflammatory responses.

A Resource Building Virtual Care Programme: improving symptoms and social functioning among female and male rural veterans.

Background: Veterans have higher rates of PTSD and depression compared to the general population and experience substantial functional impairment. Impairment in social functioning has been a significant concern among Veterans, particularly rural Veterans, who have limited access to mental health care and are at risk for social isolation. Objective: A mixed-method study was implemented to evaluate the feasibility and effectiveness of webSTAIR, a web-based skills training programme, paired with home-based telehealth sessions. It was hypothesized that the programme would lead not only to reductions in PTSD and depression but also to improvements in social functioning. Method: Participants were 80 trauma-exposed Veterans enrolled in rural-serving VHA facilities with clinically elevated symptoms of either PTSD or depression. The study directed substantial outreach efforts to rural women Veterans and those who have experienced military sexual trauma (MST). Results: Significant improvements were obtained with PTSD and depression symptoms as well as in social functioning, emotion regulation, and interpersonal problems at post-treatment and 3-month follow-up. Ratings of therapeutic alliance were high as were reports of overall satisfaction in the programme. There were no differences by gender or MST status in symptom outcomes or satisfaction. Conclusions: The results support the feasibility and effectiveness of this integrated telehealth web-based skills training programme for both male and female Veterans as well as for those with and without MST. The focus on resource building and improved functioning make this programme of particular interest. Further testing is warranted.

Antecedentes: Los veteranos tienen tasas más altas de TEPT y depresión en comparación con la población general y experimentan un deterioro funcional sustancial. El deterioro del funcionamiento social ha sido una preocupación importante entre los Veteranos, particularmente los Veteranos rurales, que tienen acceso limitado a la atención de salud mental y están en riesgo de aislamiento social, lo que contribuye significativamente a problemas de salud.Objetivo: Se implementó un estudio de método mixto para evaluar la viabilidad y efectividad de webSTAIR, un programmea de capacitación en habilidades basado en la web, combinado con sesiones de telesalud en el hogar. Se planteó la hipótesis de que el programmea conduciría no solo a reducciones en el trastorno de estrés postraumático y la depresión, sino también a mejoras en el funcionamiento social.Método: Los participantes fueron 80 Veteranos expuestos a traumas inscritos en el sistema VHA de servicio rural, con síntomas clínicamente elevados de TEPT o depresión. El estudio dirigió importantes esfuerzos de divulgación a las mujeres rurales Veteranas y aquellas que han experimentado un trauma sexual militar (TSM).Resultados: Se obtuvieron mejoras significativas con el TEPT y los síntomas de depresión, así como en el funcionamiento social, la regulación de las emociones y los problemas interpersonales en el postratamiento y en el seguimiento a los 3 meses. Las puntuaciones de la alianza terapéutica fueron altas, al igual que los informes de satisfacción general en el programmea. No hubo diferencias por sexo o estado de TSM en los resultados de los síntomas o la satisfacción.Conclusiones: Los resultados respaldan la viabilidad y efectividad de este programmea integrado de capacitación en habilidades de telesalud basado en la web para veteranos masculinos y femeninos, así como para aquellos con y sin MST. El enfoque en el desarrollo de recursos y la mejora del funcionamiento hace que este programmea sea de especial interés. Se requieren nuevos estudios.

Septal Perfoplasty for Management of Symptomatic Nasal Septal Perforation: An Alternative to Surgical Closure.

Importance: Symptomatic septal perforations are often difficult to manage and can have a significant impact on patient quality of life. Available surgical techniques for repair have demonstrated a varying rate of success, presenting a need for reliable interventions targeting symptom control. Objectives: To describe the modified surgical technique here termed septal perfoplasty. To demonstrate that creation of favorable septal perforation characteristics is effective in managing symptoms and improving patient quality of life. Design, Setting, and Participants: A retrospective review of the medical record was performed of patients who underwent the procedure of interest between July 1, 2006 and October 1, 2019 at Vanderbilt University Medical Center. All patients with symptomatic septal perforation who underwent septal perfoplasty within the timeframe reviewed were included. Septal perfoplasty was standardly performed in combination with turbinate reduction in all cases. This was combined with other indicated procedures for chronic sinusitis, repair of vestibular stenosis or nasal deformity. Main Outcomes and Measures: Creation of a well-mucosalized septal perforation, combined with patient-reported acceptable symptom control, was the primary outcome. Secondary outcomes include time to resolution, duration of follow-up, postsurgical complications, and need for further intervention. Results: Twenty patients (70% female; mean [range] age, 45.8 [15-72] years) underwent septal perfoplasty over the course of 13 years. The most common etiology of perforation was trauma (40%), presenting symptom was crusting (95%), and size of perforation repaired was large (60%). Mean follow-up was 37.6 months (range, 1-153 months). Overall, favorable perforation characteristics were created in 95% of cases by the first postoperative appointment. Acceptable symptomatic control was achieved in 18 out of 20 patients (90%), with a median time to improvement of 66 days. Eight patients required additional surgery to address chronic sinusitis or vestibular stenosis. Two patients experienced postoperative infections, treated conservatively with antibiotics. Conclusion and Relevance: Septal perfoplasty is a safe, simple, and effective method for management of symptomatic nasal septal perforation, which provides an alternative to more complicated interventions with comparable rates of symptomatic resolution. This procedure should particularly be considered for patients in which difficult repair is anticipated.

Personalized Medicine in Chronic Rhinosinusitis: Phenotypes, Endotypes, and Biomarkers.

Chronic rhinosinusitis (CRS) is a heterogeneous disease process with a complex underlying cause. Improved understanding of CRS pathophysiology has facilitated new approaches to management of the patient with CRS that rely on targeting patient-specific characteristics and individual inflammatory pathways. A more personalized approach to care will ultimately incorporate a combination of phenotypic and endotypic classification systems to guide treatment. This review summarizes current evidence with respect to CRS phenotypes and endotypes, as well as the identification of potential biomarkers with potential to guide current and future treatment algorithms.

Aberrant AICA Injury During Translabyrinthine Approach.

OBJECTIVE: To define a complication of the translabyrinthine surgical approach to the posterior fossa related to a rare variant of the anterior inferior cerebellar artery (AICA) that penetrated into the petrous temporal bone. PATIENT: A healthy 59-year-old male with a unilateral sporadic vestibular schwannoma. INTERVENTION: The patient elected to undergo a translabyrinthine approach for resection of a vestibular schwannoma. An aberrant loop of AICA was encountered during the temporal bone dissection within the petrous portion of the temporal bone. OUTCOMES: The patient suffered a presumed ischemic insult resulting in a fluctuating ipsilateral facial paresis and atypical postoperative nystagmus. RESULTS: MRI demonstrated an ischemic lesion in the vascular distribution of the right anterior-inferior cerebellar artery, including the lateral portion of the right cerebellar hemisphere, middle cerebellar peduncle, and bordering the right cranial nerve VII nucleus. His functional recovery was excellent, essentially identical to the anticipated course in an otherwise uncomplicated surgery. CONCLUSIONS: This case highlights the irregular anatomy of the AICA as well as the importance of thorough neurological exams in the postsurgical lateral skull base patient.

Interobserver Variability in the Diagnosis of High-Grade Prostatic Intraepithelial Neoplasia in a Tertiary Hospital in Northern Jordan.

Prostate intraepithelial neoplasia is described as a precursor lesion to prostatic adenocarcinoma. High-grade prostate intraepithelial neoplasia (HGPIN) is classified as both grade 2 and 3 prostate intraepithelial neoplasia due to inconsistency between pathologists' findings. In our study, we assessed the interobserver variability in the diagnosis of HGPIN among genitourinary and nongenitourinary pathologists. All cases with prostate adenocarcinoma diagnosis on needle core biopsy, radical prostatectomy, and transurethral resection of prostate (TURP) between the years 2005 and 2014 were included. In total, 191 prostate cancer cases were included: 109 needle core biopsies, 45 radical prostatectomies, and 37 TURP. All were independently reviewed by 2 urologic pathologists for the presence of HGPIN. High-grade prostate intraepithelial neoplasia was diagnosed in 65 cases (34%), among which the lesion was recognized by the reporting pathologists in 36 (55%) of the cases and was missed in 29 (45%) of the cases with a κ coefficient of 0.53. There was a moderate interobserver agreement in the diagnosis of HGPIN. Consultation with genitourinary pathologist can improve HGPIN diagnosis.

Wire bristle foreign body: Never in the same place twice.

Foreign body ingestion is a common reason for visiting the emergency room. Foreign bodies can lodge anywhere in the upper aerodigestive tract and can sometimes be difficult to extract. Wire bristles that dislodge from grill-cleaning wire brushes and which are then accidentally swallowed can be particularly challenging to remove due to their small size, propensity to become embedded, and their ability to migrate through tissues. This case reveals the speed with which wire bristle foreign bodies can migrate through tissues and exemplifies the need to obtain computerized tomography evaluations in close proximity to any planned attempt to remove them.

The utility of PAX8 and SATB2 immunohistochemical stains in distinguishing ovarian mucinous neoplasms from colonic and appendiceal mucinous neoplasm.

OBJECTIVES: It is challenging to distinguish between primary ovarian mucinous tumors and metastatic mucinous neoplasms from the lower gastrointestinal tract, including appendiceal tumors. A combination of PAX8 and SATB2 immunohistochemical stains can be used as a diagnostic tool to distinguish between these cases. RESULTS: Immunostaining for SATB2, PAX8, CK7, CK20 and CDX2 was performed on 50 ovarian mucinous neoplasms (OMN) (39 cystadenomas, 4 borderline and 7 adenocarcinomas), 63 mucinous colorectal carcinoma (CRC), and 9 appendiceal mucinous neoplasms (AMN) [8 low grade appendiceal mucinous neoplasms (LAMN) and 1 adenocarcinoma]. PAX8 was positive in 32% of OMN and negative in all CRC and AMN cases. SATB2 was expressed in 2.0% of OMN, 77.8% of AMN, and 49.2% of CRC cases. CK7 was positive in 78.0% of OMN, 33.3% of AMN, and 9.5% of CRC cases. CK20 was expressed in 24.0% of OMN, 88.9% of OMN, and 87.3% of CRC cases. CDX2 was positive in 14.0% of OMN, 100% of AMN, and 90.5% of CRC cases. PAX8 can differentiate between OMN and AMN with high specificity but low sensitivity. CDX2 is the most sensitive marker for CRC and AMN, whereas SATB2 has better specificity.

ERG expression in prostate cancer biopsies with and without high-grade prostatic intraepithelial neoplasia: a study in Jordanian Arab patients.

Background: High-grade prostatic intraepithelial neoplasia (HGPIN) is the most likely precancerous lesion for prostatic adenocarcinoma (PCa). Recent molecular studies have shown that HGPIN can harbor TMPRSS2-ERG fusion, a genetic marker also associated with PCa, which may provide an additional risk stratification tool for HGPIN, especially when present as an isolated lesion. Our aim was to assess the frequency of HGPIN and ERG expression in a cohort of prostatic needle core biopsies from Jordanian-Arab patients with PCa. Materials and methods: We studied 109 needle core biopsies from patients with PCa. Clinical data, including age and preoperative prostate specific antigen (PSA) level, were obtained from patients' medical records. Results: HGPIN was present in 31 (28.4 %) of the 109 cases. Of the HGPIN cases, 13 (41.9%) expressed ERG immunostain. ERG expression in HGPIN was independent of patient age at presentation (P=0.4), pre-operative PSA (P=0.9), and the grade, using the novel Grade Groups (P=0.5). Conclusion: The frequency of HGPIN in our cohort appears similar to the one found in the Western patient populations and demonstrates a comparable frequency of ERG expression in these lesions.

Knowledge, Attitudes, and Practices of Women Toward Prenatal Genetic Testing.

OBJECTIVES: We aim to address public knowledge, attitudes, and practices relative to prenatal genetic testing as a starting point for policy development in Jordan. STUDY DESIGN: We conducted a cross-sectional prenatal genetic testing knowledge, attitudes, and practices survey with 1111 women recruited at obstetrics and gynecology clinics nationwide. Data were analyzed using a variety of descriptive and inferential statistical tests. RESULTS: The overwhelming majority (>94%) of participants considered prenatal genetic testing, particularly non-invasive prenatal genetic screening, procedures to be good, comfortable, and reasonable, even when the non-diagnostic nature of non-invasive prenatal genetic screening was explained. Likewise, 95% encouraged the implementation of non-invasive prenatal genetic screening within the Jordanian health system, but most preferred it to remain optional. However, women in higher-risk age brackets, in consanguineous marriages, and with less education were significantly less interested in learning about non-invasive prenatal genetic screening. Only 60% of women interviewed were satisfied with the services provided by their obstetric/gynecologist. The more satisfied the women were, the more they are likely to adapt non-invasive prenatal genetic screening. CONCLUSIONS: In sum, although the data support the receptivity of Jordanian women to national implementation of non-invasive prenatal genetic screening, such policies should be accompanied by health education to increase the genetic literacy of the population and to engage high-risk populations. Thus, this offers rare insight into the readiness of 1 particular Arab population to adapt non-invasive prenatal genetic screening technologies.