Uncoordinated maturation of developing and regenerating postnatal mammalian vestibular hair cells.

Sensory hair cells are mechanoreceptors required for hearing and balance functions. From embryonic development, hair cells acquire apical stereociliary bundles for mechanosensation, basolateral ion channels that shape receptor potential, and synaptic contacts for conveying information centrally. These key maturation steps are sequential and presumed coupled; however, whether hair cells emerging postnatally mature similarly is unknown. Here, we show that in vivo postnatally generated and regenerated hair cells in the utricle, a vestibular organ detecting linear acceleration, acquired some mature somatic features but hair bundles appeared nonfunctional and short. The utricle consists of two hair cell subtypes with distinct morphological, electrophysiological and synaptic features. In both the undamaged and damaged utricle, fate-mapping and electrophysiology experiments showed that Plp1+ supporting cells took on type II hair cell properties based on molecular markers, basolateral conductances and synaptic properties yet stereociliary bundles were absent, or small and nonfunctional. By contrast, Lgr5+ supporting cells regenerated hair cells with type I and II properties, representing a distinct hair cell precursor subtype. Lastly, direct physiological measurements showed that utricular function abolished by damage was partially regained during regeneration. Together, our data reveal a previously unrecognized aberrant maturation program for hair cells generated and regenerated postnatally and may have broad implications for inner ear regenerative therapies.

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.

Methylprednisolone, venous thromboembolism, and association with heparin to 30 days in hospital survival in severe Covid-19 pneumonia.

BACKGROUND: Mortality in severe COVID-19 pneumonia is associated with thrombo-inflammation. Corticosteroids are given to attenuate the inflammation, but they are associated with thrombosis. The aims of this study were to determine the risk of venous thromboembolism between no methylprednisolone and methylprednisolone (dose versus duration) and to evaluate any synergistic dose-dependent association of heparin and methylprednisolone to 30 days in hospital survival. METHODS: This was a secondary analysis of a retrospective cohort. Patients included in this study were ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 hospitals in New Jersey, United States. A propensity score analysis between administration of methylprednisolone and no methylprednisolone was fitted for 11 variables and Youden Index Method was used to determine cut-off between low dose and high dose methylprednisolone. Multivariate cox regression was to assess risk. RESULTS: In 759 patients, the incidence of venous thromboembolism was 9% of patients who received methylprednisolone and 3% of patients who did not receive methylprednisolone with a [RR 2.92 (95% CI 1.54, 5.55 P < 0.0001)]. There was a higher incidence of mechanical ventilation in the methylprednisolone group. The median d-dimer between patients with venous thromboembolism was higher compared to those without (P < 0.0003). However, the d-dimer was not statistically significant between those who had venous thromboembolism between methylprednisolone and no methylprednisolone groups (P = 0.40). There was no higher risk in high dose versus low dose [RR = 0.524 (95% CI 0.26, 1.06 P 0.4)]; however, the risk for venous thromboembolism between methylprednisolone for > 7 days and ≤ 7 days was statistically significant (RR 5.46 95% CI 2.87, 10.34 P < 0.0001). Patients who received low dose methylprednisolone and therapeutic heparin had a trend towards higher risk of mortality compared to prophylactic heparin (HR 1.81 95% CI 0.994 to 3.294) (P = 0.0522). There was no difference in 30 days in hospital survival between high dose methylprednisolone with prophylactic or therapeutic heparin (HR 0.827 95% CI 0.514 to 1.33) (P = 0.4335). CONCLUSION: Methylprednisolone for > 7 days had a higher association of venous thromboembolism. There was no added benefit of therapeutic heparin to methylprednisolone on mechanically ventilated patients.

Thoracentesis techniques: A literature review.

Thoracentesis is performed by 4 methods: gravity, manual aspiration, vacuum-bottle suction, and wall suction. This literature review investigates the safety of these techniques and determines if there is significant difference in complication rates. A comprehensive literature search revealed 6 articles studying thoracentesis techniques and their complication rates, reviewing 20,815 thoracenteses: 80 (0.4%) by gravity, 9431 (45.3%) by manual aspiration, 3498 (16.8%) by vacuum-bottle suction, 7580 (36.4%) by wall suction and 226 (1.1%) unspecified. Of the 6 studies, 2 were smaller with 100 and 140 patients respectively. Overall, there was a 4.4% complication rate including hemothoraces, pneumothoraces, re-expansion pulmonary edema (REPE), chest discomfort, bleeding at the site, pain, and vasovagal episodes. The pneumothorax and REPE rate was 2.5%. Sub-analyzed by each method, there was a 47.5% (38/80) complication rate in the gravity group, 1.2% (115/9431) in the manual aspiration group including 0.7% pneumothorax or REPE, 8% (285/3498) in the vacuum-bottle group including 3.7% pneumothorax or REPE, 4% (309/7580) in the wall suction group all of which were either pneumothorax or REPE, and 73% (166/226) in the unspecified group most of which were vasovagal episodes. Procedure duration was less in the suction groups versus gravity drainage. The 2 smaller studies indicated that in the vacuum groups, early procedure termination rate from respiratory failure was significantly higher than non-vacuum techniques. Significant complication rate from thoracentesis by any technique is low. Suction drainage was noted to have a lower procedure time. Symptom-limited thoracentesis is safe using vacuum or wall suction even with large volumes drained. Other factors such as procedure duration, quantity of fluid removed, number of needle passes, patients' BMI, and operator technique may have more of an impact on complication rate than drainage modality. All suction modalities of drainage seem to be safe. Operator technique, attention to symptom development, amount of fluid removed, and intrapleural pressure changes may be important in predicting complication development, and therefore, may be useful in choosing which technique to employ. Specific drainage modes and their complications need to be further studied.

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.

Impact of liver cirrhosis on ST-elevation myocardial infarction related shock and interventional management, a nationwide analysis.

BACKGROUND: Critical care is rapidly evolving with significant innovations to decrease hospital stays and costs. To our knowledge, there is limited data on factors that affect the length of stay and hospital charges in cirrhotic patients who present with ST-elevation myocardial infarction-related cardiogenic shock (SRCS). AIM: To identify the factors that increase inpatient mortality, length of stay, and total hospital charges in patients with liver cirrhosis (LC) compared to those without LC. METHODS: This study includes all adults over 18 from the National Inpatient Sample 2017 database. The study consists of two groups of patients, including SRCS with LC and without LC. Inpatient mortality, length of stay, and total hospital charges are the primary outcomes between the two groups. We used STATA 16 to perform statistical analysis. The Pearson's chi-square test compares the categorical variables. Propensity-matched scoring with univariate and multivariate logistic regression generated the odds ratios for inpatient mortality, length of stay, and resource utilization. RESULTS: This study includes a total of 35798453 weighted hospitalized patients from the 2017 National Inpatient Sample. The two groups are SRCS without LC (n = 758809) and SRCS with LC (n = 11920). The majority of patients were Caucasian in both groups (67% vs 72%). The mean number of patients insured with Medicare was lower in the LC group (60% vs 56%) compared to the other group, and those who had at least three or more comorbidities (53% vs 90%) were significantly higher in the LC group compared to the non-LC group. Inpatient mortality was also considerably higher in the LC group (28.7% vs 10.63%). Length of Stay (LOS) is longer in the LC group compared to the non-LC group (9 vs 5.6). Similarly, total hospital charges are higher in patients with LC ($147407.80 vs $113069.10, P ≤ 0.05). Inpatient mortality is lower in the early percutaneous coronary intervention (PCI) group (OR: 0.79 < 0.11), however, it is not statistically significant. Both early Impella (OR: 1.73 < 0.05) and early extracorporeal membrane oxygenation (ECMO) (OR: 3.10 P < 0.05) in the LC group were associated with increased mortality. Early PCI (-2.57 P < 0.05) and Impella (-3.25 P < 0.05) were also both associated with shorter LOS compared to those who did not. Early ECMO does not impact the LOS; however, it does increase total hospital charge (addition of $24717.85, P < 0.05). CONCLUSION: LC is associated with a significantly increased inpatient mortality, length of stay, and total hospital charges in patients who develop SRCS. Rural and Non-teaching hospitals have significantly increased odds of extended hospital stays and higher adjusted total hospital charges. The Association of LC with worse outcomes outlines the essential need to monitor these patients closely and treat them early on with higher acuity care. Patients with early PCI had both shorter LOS and reduced inpatient mortality, while early Impella was associated with increased mortality and shorter LOS. Early ECMO is associated with increased mortality and higher total hospital charges. This finding should affect the decision to follow through with interventional management in this cohort of patients as it is associated with poor outcomes and immense resource utilization.

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.

Surgical Approach for Rapid and Minimally Traumatic Recovery of Human Inner Ear Tissues From Deceased Organ Donors.

OBJECTIVE: To develop a surgical approach for rapid and minimally traumatic recovery of inner ear tissue from human organ and tissue donors to provide fresh tissue for use in inner ear research. STUDY DESIGN: Exploration of novel surgical methodology and evaluation of the steps necessary for obtaining specimens from donors during the procurement of organs for transplantation. SETTING: Donor procurement locations across multiple local hospitals and tissue processing at the microsurgical temporal bone laboratory. PATIENTS TISSUE SOURCE: Human organ and tissue donors. INTERVENTIONS: Dissection and procurement of the inner ear tissue. MAIN OUTCOME MEASURES: Development of rapid and minimally traumatic inner ear tissue recovery. Primarily, establishing an efficient process which includes collaboration with transplant network, implementing a consent protocol, developing and training an on-call recovery team, and designing a portable surgical kit suitable for use in a variety of settings. RESULTS: The extraction procedure is described in three consecutive steps: the trans-canal exposure, the approach to the vestibule with extraction of the vestibular organs; and the approach to extract inner ear tissues from the cochlear duct. CONCLUSIONS: Organ and tissue donors are a promising and underutilized resource of inner ear organs for purposes of research and future translational studies. Using our modified technique through the trans-canal/trans-otic approach, we were able to extract tissues of the vestibular and auditory end organs in a timely manner.

Selection Criteria Optimal for Recovery of Inner Ear Tissues From Deceased Organ Donors.

OBJECTIVE: To identify optimal conditions for recovering viable inner ear tissues from deceased organ donors. SETTING: Tertiary recovery hospitals and Donor Network West Organ Recovery Center. INTERVENTIONS: Recovering bilateral inner ear tissues and immunohistological analysis. MAIN OUTCOME MEASURES: Immunohistochemical analysis of utricles from human organ donors after brain death (DBD) or donors after cardiac death (DCD). RESULTS: Vestibular tissues from 21 organ donors (39 ears) were recovered. Of these, 18 donors (33 utricles) were examined by immunofluorescence. The sensory epithelium was present in seven utricles (two from DBD and five from DCD). Relative to DBD utricles, DCD organs more commonly displayed dense populations of hair cells and supporting cells. Relative to DBD, DCD had significantly shorter postmortem interval time to tissue recovery (<48 h). Compared to donors with no sensory epithelium, donors with intact and viable sensory epithelium (both DCD and DBD) had significantly shorter lag time to resuscitation prior to hospital admission (6.4 ±â€Š9.2 vs 35.6 ±â€Š23.7 min, respectively) as well as a shorter time between pronouncements of death to organ recovery (22.6 ±â€Š30.4 vs 64.8 ±â€Š22.8 h, respectively). CONCLUSIONS: Organ donors are a novel resource for bilateral inner ear organs. Selecting tissue donors within defined parameters can optimize the quality of recovered inner ear tissues, thereby facilitating future research investigating sensory and nonsensory cells.

Exploring disease interrelationships in patients with lymphatic disorders: A single center retrospective experience.

BACKGROUND: The lymphatic contribution to the circulation is of paramount importance in regulating fluid homeostasis, immune cell trafficking/activation and lipid metabolism. In comparison to the blood vasculature, the impact of the lymphatics has been underappreciated, both in health and disease, likely due to a less well-delineated anatomy and function. Emerging data suggest that lymphatic dysfunction can be pivotal in the initiation and development of a variety of diseases across broad organ systems. Understanding the clinical associations between lymphatic dysfunction and non-lymphatic morbidity provides valuable evidence for future investigations and may foster the discovery of novel biomarkers and therapies. METHODS: We retrospectively analysed the electronic medical records of 724 patients referred to the Stanford Center for Lymphatic and Venous Disorders. Patients with an established lymphatic diagnosis were assigned to groups of secondary lymphoedema, lipoedema or primary lymphovascular disease. Individuals found to have no lymphatic disorder were served as the non-lymphatic controls. The prevalence of comorbid conditions was enumerated. Pairwise co-occurrence pattern analyses, validated by Jaccard similarity tests, was utilised to investigate disease-disease interrelationships. RESULTS: Comorbidity analyses underscored the expected relationship between the presence of secondary lymphoedema and those diseases that damage the lymphatics. Cardiovascular conditions were common in all lymphatic subgroups. Additionally, statistically significant alteration of disease-disease interrelationships was noted in all three lymphatic categories when compared to the control population. CONCLUSIONS: The presence or absence of a lymphatic disease significantly influences disease interrelationships in the study cohorts. As a physiologic substrate, the lymphatic circulation may be an underappreciated participant in disease pathogenesis. These relationships warrant further, prospective scrutiny and study.

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.

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.

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.

Association of polymorphisms in ADAMTS-7 gene with the susceptibility to coronary artery disease - a systematic review and meta-analysis.

OBJECTIVE: To systematically review literature evidence to discover the association of ADAMTS7 (A Disintegrin And Metalloproteinase with Thrombospondin-like motifs 7) polymorphisms and the risk of developing CAD (coronary artery disease). DATA SOURCES: A related literature search in online databases, including EMBASE, PubMed, and Web of Science was undertaken. The period covered was from 2007 to September 10, 2019. RESULTS: Of 256 citations retrieved, nine relevant studies were selected for detailed evaluation. Five SNPs (rs3825807, rs1994016, rs4380028, rs79265682, and rs28455815) in ADAMTS7 gene were identified among included studies. There were 51,851 cases and 89,998 controls included in four studies for SNP rs3825807, 13,403 cases and 11,381 controls included in two studies for SNP rs1994016, 37,838 cases and 38,245 controls included in two studies for SNP rs4380028, 3,133 cases and 5,423 controls included in one study for SNP rs79265682, 103,494 cases and 198,684 controls included in one study for SNP rs28455815. We found most consistent evidence for an association with CAD on coronary angiogram with ADAMTS7 SNP rs3825807 risk allele A in contrast to control G allele, followed by rs4380028 (C vs. T allele), and rs1994016 (C vs. T allele). CONCLUSIONS: ADAMTS7 polymorphism is likely an important risk factor for development of CAD. Our data also suggest that the ADAMTS7 polymorphism may be a risk factor for CAD progression in patients who already have pathology in their coronary arteries. REVIEW METHODS: We included all studies in English language that reported correlation between the ADAMTS7 polymorphism and CAD in human cases.

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.

Ambient Pressure Tympanometry Wave Patterns in Patients With Superior Semicircular Canal Dehiscence.

Importance: Superior semicircular canal dehiscence (SSCD) is a treatable condition, but current diagnostic modalities have numerous limitations. Clinicians would benefit from an additional tool for diagnostic workup that is both rapid and widely available. Objective: To assess the utility of ambient pressure tympanometry (APT) in the diagnostic workup of SSCD by determining the sensitivity and specificity of APT for SSCD in comparison to other diagnostic modalities. Design: Retrospective cohort study of patients who underwent APT and temporal bone computerized tomography (CT) scans from May 2017 to July 2018. Setting: Tertiary referral center. Participants: APT was performed as part of routine audiological testing on adult patients. We retrospectively analyzed all patients who received both APT and temporal bone CT scans, and divided ears into SSCD and non-SSCD groups based on the presence or absence of radiographic SSCD. Ears with other radiographic findings that could affect tympanic membrane compliance were excluded. Exposures: All patients in this study underwent APT and temporal bone CT scans. Some patients also underwent pure tone audiometry and vestibular evoked myogenic potentials (VEMPs). Main Outcomes and Measures: The primary outcome measures were sensitivity, specificity, and risk ratio of APT for SSCD. Secondary outcome measures include sensitivity of VEMPs and supranormal hearing thresholds. Results: We describe 52 patients (70 ears) who underwent APT and CT imaging (mean age 47.1 years, 67.1% female). APT detected SSCD with 66.7% sensitivity and 72.1% specificity. In symptomatic patients, sensitivity was 71.4% and specificity was 75%. VEMPs performed best at detecting SSCD when defining a positive test as oVEMP amplitude >17 µV, with a sensitivity of 68.2%, similar to APT (p > 0.99). The combination of APT and VEMPs increased sensitivity to 88.9%, better than APT alone (p = 0.031) and trending toward better than VEMPs alone (p = 0.063). Conclusions and Relevance: Rhythmic wave patterns on APT are associated with SSCD and may raise suspicion for this condition in conjunction with consistent results on other diagnostic modalities. Although clinical utility requires confirmation in a larger prospective study, APT is a simple, rapid, and widely available tool warranting further study.