Transcriptionally Active Human Papillomavirus Infection in a Minority of Esophageal Squamous Cell Carcinomas in North America.

The role of Human papillomavirus (HPV) infection in esophageal squamous cell carcinoma (ESCC) is a topic of ongoing debate. This study used two screening approaches to look for evidence of HPV infection in esophageal squamous cell carcinoma. We initially checked for HPV infection in a randomly selected group of 53 ESCC cases. We did not detect any tumors positive for high-risk HPV. However, during clinical practice, we identified an HPV-positive ESCC in the distal esophagus, which tested positive for HPV16. This index case was TP53 wild-type, as determined by next-generation DNA sequencing (NGS). Since TP53 mutations are rare in other HPV-driven cancers, we improved our screening method by limiting our screen to a subset of ESCC cases without TP53 mutations. A second screen of 95 ESCCs (from 93 patients) sequenced by NGS revealed an additional 7 ESCCs with TP53 wild-type status (7.3% of the total). Of the 7 cases, 2 cases were found to be high-risk HPV positive. Both patients also tested positive for circulating cell-free HPV DNA and had a complete response to neoadjuvant chemoradiation. The index patient had microscopic residual tumor following neoadjuvant therapy. The patient underwent adjuvant immunotherapy and remained disease free after 22 months of surveillance. This study affirms the transcriptionally active status of high-risk HPV in a minority of ESCC patients in North America.

Novel articulating through-the-scope traction device.

Video 1Parts and functions of the novel articulating traction device with its application in gastric and colonic endoscopic submucosal dissection procedures.

Primary Spinal Glioblastoma Mimicking Neuroschistosomiasis: A Case Report.

Primary glioblastoma of the spinal cord (sGB) is a rare and challenging diagnosis. In the diagnostic algorithm, reversible causes should be considered while the diagnosis of sGB is under evaluation. We present a case of cervical sGB mimicking neuroschistosomiasis. A 21-year-old Somali man presented with neck pain, sensory disturbances, and spastic tetraplegia. Cervical spine magnetic resonance imaging with contrast showed a heterogeneously enhancing intramedullary mass spanning from the level of the C1 to T3 vertebrae. Cerebrospinal fluid analysis showed a lymphocytic predominance and elevated protein. Due to the patient's history of poorly treated schistosomiasis, praziquantel and dexamethasone were initiated while the diagnostic work-up was completed. Three days after the patient was discharged to a rehabilitation facility where he experienced worsened motor function with radiographic progression of the lesion and increased cord edema. The patient underwent a surgical biopsy which confirmed a diagnosis of primary sGB. sGB is an unusual diagnosis that can masquerade as a non-neoplastic lesion. However, the diagnosis of sGB should be considered in patients with an intramedullary spinal cord lesion who exhibit rapid radiographic and clinical progression.

Astroblastomas exhibit radial glia stem cell lineages and differential expression of imprinted and X-inactivation escape genes.

Astroblastomas (ABs) are rare brain tumors of unknown origin. We performed an integrative genetic and epigenetic analysis of AB-like tumors. Here, we show that tumors traceable to neural stem/progenitor cells (radial glia) that emerge during early to later brain development occur in children and young adults, respectively. Tumors with MN1-BEND2 fusion appear to present exclusively in females and exhibit overexpression of genes expressed prior to 25 post-conception weeks (pcw), including genes enriched in early ventricular zone radial glia and ependymal tumors. Other, histologically classic ABs overexpress or harbor mutations of mitogen-activated protein kinase pathway genes, outer and truncated radial glia genes, and genes expressed after 25 pcw, including neuronal and astrocyte markers. Findings support that AB-like tumors arise in the context of epigenetic and genetic changes in neural progenitors. Selective gene fusion, variable imprinting and/or chromosome X-inactivation escape resulting in biallelic overexpression may contribute to female predominance of AB molecular subtypes.

The reliability of saliva for the detection of SARS-CoV-2 in symptomatic and asymptomatic patients: Insights on the diagnostic performance and utility for COVID-19 screening.

Current literature has focused on testing saliva in symptomatic patients, and little information is available regarding saliva performance in asymptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. We compared paired saliva and nasopharyngeal swabs (NPS) collected from 33 symptomatic and 12 asymptomatic known SARS-CoV-2-positive patients. Saliva had an overall sensitivity of 59%, a specificity of 95%, and a negative predictive value of 98%. Saliva demonstrated higher sensitivity in symptomatic (80%) vs. asymptomatic individuals (36%) (P = 0.006), and in high-risk (symptomatic, febrile and/or with comorbidities) (82%) vs. low-risk (asymptomatic, afebrile, and no comorbidities) (22%) patients (P = 0.0002). Cycle threshold (Ct) values in NPS specimens were higher in saliva-negative vs. saliva-positive cases (P = 0.02 and <0.001). Overall, these findings show that despite saliva's low sensitivity in asymptomatic SARS-CoV-2 infections, it can detect infections with lower Ct values and a potentially higher chance of viral transmission. Additional studies are warranted to fully evaluate saliva as a screening test for coronavirus disease-2019.

Aurora-A kinase is differentially expressed in the nucleus and cytoplasm in normal Müllerian epithelium and benign, borderline and malignant serous ovarian neoplasms.

BACKGROUND: Aurora-A kinase is important for cellular proliferation and is implicated in the tumorigenesis of several malignancies, including of the ovary. Information regarding the expression patterns of Aurora-A in normal Müllerian epithelium as well as benign, borderline and malignant epithelial ovarian neoplasms is limited. METHODS: We investigated Aurora-A expression by immunohistochemistry in 15 benign, 19 borderline and 17 malignant ovarian serous tumors, and 16 benign, 8 borderline, and 2 malignant ovarian mucinous tumors. Twelve fimbriae from seven patients served as normal Müllerian epithelium controls. We also examined Aurora-A protein expression by western blot in normal fimbriae and tumor specimens. RESULTS: All normal fimbriae (n = 12) showed nuclear but not cytoplasmic Aurora-A immunoreactivity by immunohistochemistry. Benign ovarian tumors also showed strong nuclear Aurora-A immunoreactivity. Forty-eight percent (13/27) of borderline tumors demonstrated nuclear Aurora-A immunoreactivity, while the remainder (52%, 14/27) lacked Aurora-A staining. Nuclear Aurora-A immunoreactivity was absent in all malignant serous tumors, however, 47% (8/17) demonstrated perinuclear cytoplasmic staining. These results were statistically significant when tumor class (benign/borderline/malignant) was compared to immunoreactivity localization or intensity (Fisher Exact Test, p < 0.01). Western blot analysis confirmed the greater nuclear Aurora-A expression in control Müllerian epithelium compared to borderline and malignant tumors. CONCLUSION: Aurora-A kinase is differentially expressed across normal Müllerian epithelium, benign and borderline serous and mucinous ovarian epithelial neoplasms and malignant serous ovarian tumors., with nuclear expression of unphosphorylated Aurora-A being present in normal and benign neoplastic epithelium, and lost in malignant serous neoplasms. Further studies of the possible biological and clinical implications of the loss of nuclear Aurora-A expression in ovarian tumors, and its role in ovarian carcinogenesis are warranted.

Plasma resuscitation with adjunctive peritoneal resuscitation reduces ischemic intestinal injury following hemorrhagic shock.

INTRODUCTION: Impaired intestinal microvascular perfusion following resuscitated hemorrhagic shock (HS) leads to ischemia-reperfusion injury, microvascular dysfunction, and intestinal epithelial injury, which contribute to the development of multiple organ dysfunction syndrome in some trauma patients. Restoration of central hemodynamics with traditional methods alone often fails to fully restore microvascular perfusion and does not protect against ischemia-reperfusion injury. We hypothesized that resuscitation (RES) with fresh frozen plasma (FFP) alone or combined with direct peritoneal resuscitation (DPR) with 2.5% Delflex solution might improve blood flow and decrease intestinal injury compared with conventional RES or RES with DPR alone. METHODS: Sprague-Dawley rats underwent HS (40% mean arterial pressure) for 60 minutes and were randomly assigned to a RES group (n = 8): sham, HS-crystalloid resuscitation (CR) (shed blood + two volumes CR), HS-CR-DPR (intraperitoneal 2.5% peritoneal dialysis fluid), HS-FFP (shed blood + two volumes FFP), and HS-DPR-FFP (intraperitoneal dialysis fluid + two volumes FFP). Laser Doppler flowmeter evaluation of the ileum, serum samples for fatty acid binding protein enzyme-linked immunosorbent assay, and hematoxylin and eosin (H&E) staining were used to assess intestinal injury and blood flow. p Values of <0.05 were considered significant. RESULTS: Following HS, the addition of DPR to either RES modality improved intestinal blood flow. Four hours after resuscitated HS, FABP-2 (intestinal) and FABP-6 (ileal) were elevated in the CR group but reduced in the FFP and DPR groups. The H&E staining demonstrated disrupted intestinal villi in the FFP and CR groups, most significantly in the CR group. Combination therapy with FFP and DPR demonstrated negligible cellular injury in H&E graded samples and a significant reduction in fatty acid binding protein levels. CONCLUSION: Hemorrhagic shock leads to ischemic-reperfusion injury of the intestine, and both FFP and DPR alone attenuated intestinal damage; combination FFP-DPR therapy alleviated most signs of organ injury. Resuscitation with FFP-DPR to restore intestinal blood flow following shock could be an essential method of reducing morbidity and mortality after trauma.