Pneumatosis Intestinalis Following Surgical Gastrostomy Tube Placement in a Patient With Glottic Squamous Cell Carcinoma: A Case Report.

Pneumatosis intestinalis (PI) is a rare medical and post-surgical sequela of multiple different etiologies which can be either benign or life-threatening. Various mechanisms have been proposed to explain the occurrence of PI; however, the pathophysiology is dependent on the suspected cause. The condition is largely categorized into two broad groups: idiopathic PI, which remains relatively uncommon, and secondary PI. The latter often surfaces as a result of a wide array of both gastrointestinal and non-gastrointestinal illnesses. These encompass vascular compromise, bowel mucosal disruption, gastrointestinal dysmotility, as well as infectious and immunological etiologies. Management ranges from conservative medical strategies to emergent surgical intervention. We present the first case to our knowledge of spontaneous PI developing within five days of a surgical gastrostomy tube (SGT) placement in a 79-year-old female with glottic squamous cell carcinoma which unfortunately proved fatal. The purpose of this case report is to highlight a rare fatal complication of a common surgical procedure and the necessity of initiating interdisciplinary management quickly to determine the best treatment course.

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

Unusual Presentation of Gallbladder Fossa Abscess Following Open Cholecystectomy in a Patient With Cholecystitis: A Case Report.

Cholecystectomy is one of the most commonly performed surgical interventions, and laparoscopic cholecystectomy is the standard intervention with open cholecystectomies having declined nowadays. Similar to other surgical procedures, cholecystectomy carries its own risks including sepsis, bleeding, damage to surrounding tissues, bile leakage, and abscess formation. Abscess formation can be due to a variety of reasons such as infection or gallstone spillage during surgery with the latter being more common to laparoscopic surgery. Here we describe a patient with an unusual presentation of gallbladder fossa abscess following open cholecystectomy.

Progressive Dysphagia in Patient With Cervical Plate Complicated With Posterior Pharyngeal Wall Erosion.

A 58-year-old male patient with a history of Parkinson's disease and solitary cervical spinal sarcoma underwent corpectomy, a fusion of C3-C6 with cervical fixation plate placement, and stereotactic body radiation therapy, presented 18 months following surgery with dysphagia, concomitant with weakness, diplopia. The initial workup in cervical magnetic resonance imaging (MRI) revealed aerodigestive tract soft tissue enhancement. Dysphagia progressed during hospitalization, and the patient was intubated due to aspiration pneumonia and respiratory failure. Further evaluations with esophagogastroduodenoscopy (EGD) revealed posterior pharyngeal wall, upper cervical esophageal erosion, and the presence of a cervical fixation plate in the hypopharynx.

A Rare Cause of Liver Cirrhosis and Gastritis: Primary Gastrointestinal Amyloidosis in a Patient With Multiple Myeloma.

A 65-year-old male with a 25-year history of chronic alcoholism presented to the emergency department for a two-week history of non-radiating right upper quadrant abdominal pain associated with pruritus, nausea, coffee-ground emesis, and clay-colored stools. The exam was notable for icteric sclera, right upper quadrant abdominal tenderness, ascites, and hepatomegaly. Initial workup revealed new-onset unexplained elevated liver enzyme. The CT scan revealed diffuse liver cirrhosis, periportal lymphadenopathy, and stigmata of portal hypertension including hepatosplenomegaly, ascites, and varices. Esophagogastroduodenoscopy (EGD) with endoscopic ultrasound was performed, which showed gastritis and enlarged porta hepatis, which was ultimately biopsied and revealed extracellular amyloid deposition in peri-sinusoidal spaces consistent with amyloidosis. Transesophageal echocardiogram raised suspicion for cardiac involvement with amyloid deposit. The patient was started on steroids and chemotherapy with daratumumab, however his condition was complicated by septic shock, which led to an admission in the ICU followed by endotracheal intubation and multi-organ failure and eventual palliative care. Our case highlights the importance of clinical suspicion of GI amyloidosis in patients with constitutional symptoms including fatigue, weight loss, and unexplained liver disease. Once amyloidosis is considered, the diagnosis can be obtained by tissue biopsy from either the GI tract or subcutaneous adipose tissue.

Racial/ethnic disparities on inflammation and response to methylprednisolone in severe COVID-19 pneumonia.

BACKGROUND: Racial/ethnic minorities are at higher risk for severe COVID-19. This may be related to social determinants that lead to chronic inflammatory states. The aims of the study were to determine if there are racial/ethnic disparities with inflammatory markers and association of methylprednisolone to in hospital survival. METHODS: This was a secondary analysis of a retrospective cohort study of patients ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 Hospitals in New Jersey, United States. Patients who received other formulation of corticosteroids were not included. Area under the receiver operating characteristics curves were performed to test for discriminatory ability of each inflammatory makers. Univariate and multivariate Cox regression assessed the association of variables to in hospital survival. RESULTS: Propensity matched sample (n = 759) between no methylprednisolone (n = 380) and methylprednisolone (n = 379) had 338 Whites, 102 Blacks, 61 Asian/Indians, and 251 non-Black non-White Hispanics. Compared to CRP, area under receiving operating characteristic curve for d-dimer in Hispanics (0.742) was statistically different (DeLong Test P = 0.0041). Multivariate cox regression showed that different variables in Blacks [age ≥ 60 years (HR = 3.71, P = 0.0281), mechanical ventilation (HR = 5.07, P = 0.0281) and creatinine ≥ 1.5 mg/dL (HR = 3.61, P = 0.0007)], Whites [cancer (HR = 1.68, P = 0.0213), qSOFA score of 1 (HR = 1.81, P = 0.0213), qSOFA score of 2 (HR = 5.16, P < 0.0001), qSOFA score of 3 (HR = 11.81, P < 0.0001) and creatinine ≥ 1.5 mg/dL (HR = 2.16, P = 0.0006)], Hispanics [hypertension (HR = 2.52, P = 0.0007), cancer (HR = 2.99, P = 0.0244 and D-dimer ≥ 2 mcg/mL (HR = 2.22, P = 0.0077)], and Asian/Indians [ chronic kidney disease (HR = 6.36, P = 0.0031) and CRP > 20 mg/L (HR = 5.02, P = 0.0032)] were statistically significant for mortality. Low dose and high dose methylprednisolone were significantly associated with prolonged survival in Whites [low dose (HR = 0.37, P < 0.0001) and high dose (HR = 0.48, P < 0.0183)] and Asian/Indians [low dose (HR = 0.13, P = 0.0101) and high dose (HR = 0.15, P = 0.01)]. However, high dose was not associated with improved survival compared to low dose. Methylprednisolone was not associated with prolonged survival in Blacks and Hispanics. CONCLUSION: Racial/Ethnic disparities with inflammatory markers preclude the use of one marker as a predictor of survival. Methylprednisolone is associated with prolonged survival in Asian/Indians and Whites.

RNA-Binding Proteins CLK1 and POP7 as Biomarkers for Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma.

The abnormality of RNA-binding proteins (RBPs) is closely related to the tumorigenesis and development of esophageal squamous cell carcinoma (ESCC), and has been an area of interest for research recently. In this study, 162 tumors and 11 normal samples are obtained from The Cancer Genome Atlas database, among which 218 differentially expressed RBPs are screened. Finally, a prognostic model including seven RBPs (CLK1, DDX39A, EEF2, ELAC1, NKRF, POP7, and SMN1) is established. Further analysis reveals that the overall survival (OS) rate of the high-risk group is lower than that of the low-risk group. The area under the receiver operating characteristic (ROC) curve (AUC) of the training group and testing group is significant (AUCs of 3 years are 0.815 and 0.694, respectively, AUCs of 5 years are 0.737 and 0.725, respectively). In addition, a comprehensive analysis of seven identified RBPs shows that most RBPs are related to OS in patients with ESCC, among which EEF2 and ELCA1 are differentially expressed at the protein level of ESCC and control tissues. CLK1 and POP7 expressions in esophageal cancer tumor samples are undertaken using the tissue microarray, and show that CLK1 mRNA levels are relatively lower, and POP7 mRNA levels are higher compared with non-cancerous esophageal tissues. Survival analysis reveals that a higher expression of CLK1 predicts a significant worse prognosis, and a lower expression of POP7 predicts a worse prognosis in esophageal cancer. These results suggest that CLK1 may promote tumor progression, and POP7 may hinder the development of esophageal cancer. In addition, gene set enrichment analysis reveals that abnormal biological processes related to ribosomes and abnormalities in classic tumor signaling pathways such as TGF-ß are important driving forces for the occurrence and development of ESCC. Our results provide new insights into the pathogenesis of ESCC, and seven RBPs have potential application value in the clinical prognosis prediction of ESCC.

Systematic Analysis of Survival-Associated Alternative Splicing Signatures in Thyroid Carcinoma.

Alternative splicing (AS) is a key mechanism involved in regulating gene expression and is closely related to tumorigenesis. The incidence of thyroid cancer (THCA) has increased during the past decade, and the role of AS in THCA is still unclear. Here, we used TCGA and to generate AS maps in patients with THCA. Univariate analysis revealed 825 AS events related to the survival of THCA. Five prognostic models of AA, AD, AT, ES, and ME events were obtained through lasso and multivariate analyses, and the final prediction model was established by integrating all the AS events in the five prediction models. Kaplan-Meier survival analysis revealed that the overall survival rate of patients in the high-risk group was significantly shorter than that of patients in the low-risk group. The ROC results revealed that the prognostic capabilities of each model at 3, 5, and 8 years were all greater than 0.7, and the final prognostic capabilities of the models were all greater than 0.9. By reviewing other databases and utilizing qPCR, we verified the established THCA gene model. In addition, gene set enrichment analysis showed that abnormal AS events might play key roles in tumor development and progression of THCA by participating in changes in molecular structure, homeostasis of the cell environment and in cell energy. Finally, a splicing correlation network was established to reveal the potential regulatory patterns between the predicted splicing factors and AS event candidates. In summary, AS should be considered an important prognostic indicator of THCA. Our results will help to elucidate the underlying mechanism of AS in the process of THCA tumorigenesis and broaden the prognostic and clinical application of molecular targeted therapy for THCA.

Development and validation of a RNA binding protein-associated prognostic model for head and neck squamous cell carcinoma.

Evidence shows that defects in RNA-binding proteins (RBPs) are closely related to the occurrence and development of HNSCC. We obtained 502 tumors and 44 normal samples from the TCGA database, among which 190 differentially expressed RBPs were screened. Finally, a prognostic model containing nine RBPs (CELF2, CPEB1, DDX39B, EIF3L, EZH2, KHDRBS3, RNASE10, RNASE3 and SIDT1) was produced. Further analysis showed that the overall survival rate in the high-risk group was lower than that in the low-risk group. The area under the ROC curve (AUC) in the training and testing groups was significant (3-year AUC, 0.735 vs 0.796; 5-year AUC, 0.821 vs 0.804). In addition, a comprehensive analysis of nine identified RBPs showed that most of them were related to the OS of HNSCC patients, and three of them (CELF2, EZH2, and SIDT1) were differentially expressed in HNSCC and control tissues at the protein level. In addition, our data revealed that the identified RBPs are highly interconnected, with high frequency copy number changes in HNSCC samples. GSEA indicated that the abnormal biological processes related to RNA and the activation of some classical tumor signaling pathways were important driving forces for the development of HNSCC. Our results provide novel insights into the pathogenesis of HNSCC, among which nine RBP markers have potential application value in clinical decision-making and individualized treatment of HNSCC.

Development and validation of a survival model for thyroid carcinoma based on autophagy-associated genes.

Abnormalities in autophagy-related genes (ARGs) are closely related to the occurrence and development of thyroid carcinoma (THCA). However, the effect of ARGs on the prognosis of THCA remains unclear. Here, by analyzing data from TCGA, 26 differentially expressed ARGs were screened. Cox regression and Lasso regression were utilized to analyze the prognosis of the training group, and a risk model was constructed. Our results show that low-risk patients had better overall survival (OS) than high-risk patients, and the area under the ROC curve in the training and testing groups was significant (3-year AUC, 0.735 vs 0.796; 5-year AUC, 0.821 vs 0.804). In addition, a comprehensive analysis of the 5 identified ARGs demonstrated that most of them were related to OS in THCA patients, and two of them (CX3CL1 and CDKN2A) were differentially expressed in THCA and normal thyroid tissues at the protein level. GSEA suggested that the inactivation of the cell defense system and the activation of some classical tumor signaling pathways are important driving forces for the progression of THCA. This study demonstrated that the 5 ARGs in the survival model are promising multidimensional biomarkers for the diagnosis, prognosis, and treatment of THCA.

Identification of candidate aberrantly methylated and differentially expressed genes in Esophageal squamous cell carcinoma.

Aberrant methylated genes (DMGs) play an important role in the etiology and pathogenesis of esophageal squamous cell carcinoma (ESCC). In this study, we aimed to integrate three cohorts profile datasets to ascertain aberrant methylated-differentially expressed genes and pathways associated with ESCC by comprehensive bioinformatics analysis. We downloaded data of gene expression microarrays (GSE20347, GSE38129) and gene methylation microarrays (GSE52826) from the Gene Expression Omnibus (GEO) database. Aberrantly differentially expressed genes (DEGs) were obtained by GEO2R tool. The David database was then used to perform Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome pathway enrichment analyses on selected genes. STRING and Cytoscape software were used to construct a protein-protein interaction (PPI) network, then the modules in the PPI networks were analyzed with MCODE and the hub genes chose from the PPI networks were verified by Oncomine and TCGA database. In total, 291 hypomethylation-high expression genes and 168 hypermethylation-low expression genes were identified at the screening step, and finally found six mostly changed hub genes including KIF14, CDK1, AURKA, LCN2, TGM1, and DSG1. Pathway analysis indicated that aberrantly methylated DEGs mainly associated with the P13K-AKT signaling, cAMP signaling and cell cycle process. After validation in multiple databases, most hub genes remained significant. Patients with high expression of AURKA were associated with shorter overall survival. To summarize, we have identified six feasible aberrant methylated-differentially expressed genes and pathways in ESCC by bioinformatics analysis, potentially providing valuable information for the molecular mechanisms of ESCC. Our data combined the analysis of gene expression profiling microarrays and gene methylation profiling microarrays, simultaneously, and in this way, it can shed a light for screening and diagnosis of ESCC in future.

The Effect of Endoscopic Sinus Surgery on Eustachian Tube Dysfunction Symptoms.

OBJECTIVE: We assessed how eustachian tube dysfunction (ETD) changed with endoscopic sinus surgery (ESS) and identified factors associated with improvement. STUDY DESIGN: Retrospective chart review. SETTING: Academic center. SUBJECTS AND METHODS: Patients undergoing ESS for chronic rhinosinusitis with and without nasal polyposis (CRSwNP, CRSsNP) or recurrent acute rhinosinusitis (RARS) completed the Eustachian Tube Dysfunction Questionnaire 7 (ETDQ-7) preoperatively and postoperatively at 2 weeks, 6 weeks, 3 months, and 6 months. Included in analyses were demographics, comorbidities, Sinonasal Outcome Test 22 (SNOT-22), radiographic score, endoscopy score, procedure, and medication use. Regression analysis identified factors associated with improvement, defined as ΔETDQ-7 >3.5. RESULTS: In total, 302 patients were studied. ETD prevalence was 68% in CRSsNP, 48% in CRSwNP, and 88% in RARS. Patients with ETD had a mean baseline ETDQ-7 of 25.8 ± 8.0 and improved postoperatively at 2 weeks (19.9 ± 8.1, P < .001), 6 weeks (17.8 ± 9.3, P < .001), 3 months (16.8 ± 8.5, P < .001), and 6 months (16.4 ± 7.9, P < .001). At 6 months, ETD improved in 89% of patients with CRSsNP, 68% with CRSwNP, and 78% with RARS. On multivariate analysis, ETD improvement was associated with higher preoperative ETDQ-7 score (adjusted odds ratio [aOR], 1.12; 95% confidence interval [CI], 1.04-1.22; P = .030), higher preoperative SNOT-22 score (aOR, 1.02; 95% CI, 1.02-1.08; P = .001), higher preoperative SNOT-22 ear subscore (aOR, 1.27; 95% CI, 1.02-1.65; P = .034), posterior ethmoidectomy (aOR, 1.59; 95% CI, 1.22-4.92; P = .025), and postoperative corticosteroid spray use (aOR, 1.57; 95% CI, 1.17-1.66; P = .008). CONCLUSION: ETD symptoms often improve following ESS. Factors associated with improvement include higher preoperative disease burden, posterior ethmoidectomy, and postoperative corticosteroid spray. LEVEL OF EVIDENCE: 4.

DNA methylation biomarkers for nasopharyngeal carcinoma.

BACKGROUND: Aberrant methylation of DNA plays an important role in the pathogenesis of nasopharyngeal carcinoma (NPC). In the current study, we aimed to integrate three cohorts profile datasets to identify abnormally methylated-differentially expressed genes and pathways associated with NPC. METHODS: Data of gene expression microarrays (GSE53819, GSE412452) and gene methylation microarrays (GSE52068) obtained from the GEO database. Aberrantly methylated differentially expressed genes (DEGs) were obtained by GEO2R. The David database was utilized to perform enrichment and functional analysis regarding selected genes. To create a protein-protein interaction (PPI), STRING and Cytoscape software were utilized. The MCODE was used for module analysis of the PPI network. RESULTS: In total, 181 hypomethylation-high expression genes were identified, which were enriched in the biological mechanisms involved in the differentiation of endodermal cell, mitotic nuclear division, mitotic cell cycle process, chromosome segregation and cell cycle phase transition, etc. Pathway enrichment showed ECM-receptor interaction, PI3K-Akt signaling pathway, Focal adhesion, Protein digestion and absorption and Amoebiasis, etc. The top 3 hub genes of PPI network were FANCI, POSTN, and IFIH1. Additionally, 210 hypermethylation-low expression genes were identified, and our data revealed enrichment in biological processes including axoneme assembly, micro tubular formation, assembly of axonemal dynein complex, cilium movement and cilium organization, etc. Pathway analysis indicated enrichment in B cell receptor signaling pathway, Hematopoietic cell lineage, Leukocyte transendothelial migration, Complement and coagulation cascades and Fc gamma R-mediated phagocytosis, etc. The ZMYND10, PACRG and POU2AF1 were identified as the top three hub genes of PPI network. After validation in TCGA and GEPIA database, most hub genes remained significant. Patients with high expression of POSTN found to have shorter overall survival, while in patients with high expression of ZMYND10 and POU2AF1 longer overall survival was identified. CONCLUSIONS: The data revealed novel aberrantly methylated-differentially expressed genes and pathways in NPC by bioinformatics analysis, potentially providing novel insights for the molecular mechanisms governing NPC progression. Hub genes including FANCI, POSTN, IFIH1, ZMYND10, PACRG and POU2AF1 might serve as novel biomarkers for precision diagnosis and providing medical treatment for patient with NPC.

Rhythmic Wave Patterns on Ambient Pressure Tympanometry in Patients With Objective Tinnitus-associated Pathologies.

OBJECTIVE: To introduce the concept of ambient pressure tympanometry (APT) and its association with pathologies that may present with objective tinnitus. STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Audiologists performed APT on adult patients as part of routine audiological testing. Ears with myoclonus and patulous Eustachian tube (PET) were identified via review of patient history and physical examination. All other conditions were verified via computed tomography (CT) temporal bone imaging. Ears with conditions that could impair tympanic membrane compliance, such as otosclerosis or tympanic membrane perforation, were excluded. APT findings were analyzed via a novel algorithm. RESULTS: A radiographic finding associated with objective tinnitus was confirmed in 67 ears that underwent CT imaging; 45 (67%) of these ears displayed rhythmic APT wave patterns. These included 28 ears with superior semicircular canal dehiscence, 4 ears with sigmoid sinus dehiscence, 6 ears with internal carotid artery dehiscence, 4 ears with glomus tumor, and 3 ears with encephalocele. In addition, we identified three ears with myoclonus and one ear with PET. In a subset of 30 ears with objective tinnitus symptoms that underwent CT imaging, 22 displayed rhythmic waves; of these 22 ears, 20 (91%) had a radiographic finding associated with objective tinnitus. CONCLUSIONS: Rhythmic APT wave patterns are common and may be associated with numerous temporal bone pathologies that may present with objective tinnitus. APT is a simple, rapid, and widely available tool that warrants further study to determine its value in screening of these otologic conditions.

Temporal Bone CT Scan for Malleal Ligaments Assessment.

OBJECTIVE: To determine the feasibility of using temporal bone computed tomography (CT) scans to identify malleal ligaments and the prevalence of calcification in malleal ligaments. STUDY DESIGN: Retrospective case review. CT scans were blindly and retrospectively reviewed by two physicians (a radiologist and a nonradiologist). Scans differed by slice thickness, and included both conventional CT and cone beam CT (CBCT). SETTING: Ambulatory tertiary referral center. PATIENTS: One hundred fifty-one temporal bone CT scans, obtained between the years 2014 and 2017, were initially screened, which included 302 ears. Patients with previous tympanomastoid surgery or middle ear opacification were excluded, leaving 187 ears in the study. INTERVENTION: Diagnostic. MAIN OUTCOME MEASURE: Percentage of visible normal and calcified malleal ligaments. RESULTS: Scans with submillimeter slice thickness were more likely to demonstrate all three malleal ligaments than those with 1 ml and larger slices (83.7% versus 50.0% for nonradiologist, p < 0.0001; 59.6 versus 34.8% for radiologist, p < 0.0001). Calcification was seen in 11.8% of ears reviewed. The ability to detect malleal ligaments with cone beam CT was 86.2%, while the rate with conventional CT was 71.1%, a difference that persisted when controlling for slice thickness. Interobserver agreement for the detection of malleal ligaments was 65% with a Cohen's kappa coefficient of κ = 0.27. CONCLUSION: Visualization of the malleal ligaments using CT scans is feasible in a majority of aerated ears. Detection of malleal ligaments improves with thinner slice thickness and cone-beam technique. Low interobserver agreement suggests the importance of experience and a need for standardized review.