Glioma stem cell proliferation and tumor growth are promoted by nitric oxide synthase-2.

Malignant gliomas are aggressive brain tumors with limited therapeutic options, and improvements in treatment require a deeper molecular understanding of this disease. As in other cancers, recent studies have identified highly tumorigenic subpopulations within malignant gliomas, known generally as cancer stem cells. Here, we demonstrate that glioma stem cells (GSCs) produce nitric oxide via elevated nitric oxide synthase-2 (NOS2) expression. GSCs depend on NOS2 activity for growth and tumorigenicity, distinguishing them from non-GSCs and normal neural progenitors. Gene expression profiling identified many NOS2-regulated genes, including the cell-cycle inhibitor cell division autoantigen-1 (CDA1). Further, high NOS2 expression correlates with decreased survival in human glioma patients, and NOS2 inhibition slows glioma growth in a murine intracranial model. These data provide insight into how GSCs are mechanistically distinct from their less tumorigenic counterparts and suggest that NOS2 inhibition may be an efficacious approach to treating this devastating disease.

Glioma cancer stem cells secrete Gremlin1 to promote their maintenance within the tumor hierarchy.

Glioblastomas are the most prevalent and lethal primary brain tumor and are comprised of hierarchies with self-renewing cancer stem cells (CSCs) at the apex. Like neural stem cells (NSCs), CSCs reside in functional niches that provide essential cues to maintain the cellular hierarchy. Bone morphogenetic proteins (BMPs) instruct NSCs to adopt an astrocyte fate and are proposed as anti-CSC therapies to induce differentiation, but, paradoxically, tumors express high levels of BMPs. Here we demonstrate that the BMP antagonist Gremlin1 is specifically expressed by CSCs as protection from endogenous BMPs. Gremlin1 colocalizes with CSCs in vitro and in vivo. Furthermore, Gremlin1 blocks prodifferentiation effects of BMPs, and overexpression of Gremlin1 in non-CSCs decreases their endogenous BMP signaling to promote stem-like features. Consequently, Gremlin1-overexpressing cells display increased growth and tumor formation abilities. Targeting Gremlin1 in CSCs results in impaired growth and self-renewal. Transcriptional profiling demonstrated that Gremlin1 effects were associated with inhibition of p21(WAF1/CIP1), a key CSC signaling node. This study establishes CSC-derived Gremlin1 as a driving force in maintaining glioblastoma tumor proliferation and glioblastoma hierarchies through the modulation of endogenous prodifferentiation signals.

The Lgr5 transgene is expressed specifically in glycinergic amacrine cells in the mouse retina.

Retinal amacrine cells are a diverse set of interneurons within the inner nuclear layer. The canonical Wnt pathway is highly active within mature amacrine cells, but its role remains unclear. Leucine-rich repeat containing G-protein receptor 5 (Lgr5) is a newly identified component of the Wnt receptor complex that potentiates beta-catenin signaling. In multiple epithelial organs Lgr5 marks adult tissue stem cells. We investigated the expression of this gene using Lgr5-eGFP-IRES-CreER transgenic reporter mice. In the eye, Lgr5 was exclusively expressed in glycinergic amacrine cells in adult mice. Amacrine cells are post-mitotic and represent the first neuronal and non-stem cell lineage to express Lgr5. We further interrogated the spatiotemporal labeling of individual amacrine cells with controlled fluorophore expression. This "fluorofilling" technique provides a tool to study amacrine morphology and dissect neural networks.

Targeted hepatitis C screening among ex-injection drug users in the community.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is one of the leading causes of cirrhosis and hepatocellular carcinoma worldwide. It is highly prevalent among injection drug users (IDUs) but is often undiagnosed because they represent an underprivileged group that faces multiple barriers to medical care. Here, we report the results of the New Life New Liver Project, which provides targeted HCV screening and education for ex-IDUs in the community. METHODS: Patients were recruited through the social worker networks and referrals by fellow ex-IDUs, and rapid diagnosis was based on point-of-care anti-HCV testing at rehabilitation centers. RESULTS: From 2009 to 2012, we served 234 subjects. One hundred thirty (56%) subjects were anti-HCV positive. The number needed to screen to detect one patient with positive anti-HCV was 1.8 (95% confidence interval, 1.6-2.0). However, only 69 (53%) HCV patients attended subsequent follow-up at regional hospitals, and 26 (20%) received antiviral therapy. Patients who attended follow-up were older, had higher education level and more active disease as evidenced by higher alanine aminotransferase, HCV RNA, and liver stiffness measurement by transient elastography. CONCLUSIONS: Targeted screening in ex-IDUs is effective in identifying patients with HCV infection in the community. Improvement in the referral system and introduction of interferon-free regimens are needed to increase treatment uptake.

Acute myeloid leukemia: An unusual manifestation of the trachea.

Objectives: Hematologic malignancy involving the trachea is rare. It is even less common for tracheal involvement to be the initial manifestation of this disease. We present a case report highlighting an unusual diagnosis of acute myeloid leukemia (AML) that first presented with prominent tracheal manifestations. There have been only three other published case reports of extramedullary AML with involvement of the trachea. Methods: We discuss direct laryngoscopy and bronchoscopy findings, including pinkish-white irregular lesions, which were similar to findings described in the available literature for tracheal AML. Results: Laboratory findings from our case are reported, including peripheral smear demonstrating 57% blasts and bone marrow biopsy confirming the diagnosis of AML, and the relevance of these findings is discussed. Conclusion: In patients with unusual airway lesions, laboratory testing and a comprehensive airway evaluation including biopsy are necessary to narrow the differential diagnosis. Level of Evidence: 5.

Diagnosis and Management of Retrograde Cricopharyngeal Dysfunction: A Systematic Review.

Objective: Retrograde cricopharyngeal dysfunction (R-CPD) is a syndrome with rapidly increasing awareness since being first described in March 2019. As such, few cases of R-CPD are currently reported in the literature. The goal of this study is to provide a comprehensive systematic review of the available literature on R-CPD, including patient characteristics, diagnosis, and management. Data Sources: PubMed, Scopus, EMBASE. Review Methods: A systematic review of the available English literature was conducted using the data sources PubMed, Scopus, and EMBASE. Studies with original data of patients experiencing classic symptoms of R-CPD were included. Independent abstract screening followed by full-text screening was performed to assess study eligibility. Data extraction of patient demographics, symptoms, treatment, and follow-up were subsequently performed. Results: Common presentations of R-CPD include abelchia (100%), abdominal bloating (83%), and gurgling noises (75%). 554 (86.9%) patients had improved symptoms after initial treatment with BTX. The most common initial dose was 50 units in 204 (37.3%) patients. Subsequent BTX injections resolved symptoms in 40 (80%) patients. Six patients ultimately received CP myotomy for recurrent symptoms, resulting in long-term resolution in 4 (67%) patients. Conclusion: R-CPD is a newly recognized syndrome with effective treatment options including botulinum toxin injections and cricopharyngeal myotomy, where appropriate. Diagnostic modalities including esophageal manometry may aid in the initial work up of R-CPD, however further studies are required to assess its diagnostic utility.

ChatGPT Responses to Frequently Asked Questions on Ménière's Disease: A Comparison to Clinical Practice Guideline Answers.

Objective: Evaluate the quality of responses from Chat Generative Pre-Trained Transformer (ChatGPT) models compared to the answers for "Frequently Asked Questions" (FAQs) from the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) Clinical Practice Guidelines (CPG) for Ménière's disease (MD). Study Design: Comparative analysis. Setting: The AAO-HNS CPG for MD includes FAQs that clinicians can give to patients for MD-related questions. The ability of ChatGPT to properly educate patients regarding MD is unknown. Methods: ChatGPT-3.5 and 4.0 were each prompted with 16 questions from the MD FAQs. Each response was rated in terms of (1) comprehensiveness, (2) extensiveness, (3) presence of misleading information, and (4) quality of resources. Readability was assessed using Flesch-Kincaid Grade Level (FKGL) and Flesch Reading Ease Score (FRES). Results: ChatGPT-3.5 was comprehensive in 5 responses whereas ChatGPT-4.0 was comprehensive in 9 (31.3% vs 56.3%, P = .2852). ChatGPT-3.5 and 4.0 were extensive in all responses (P = 1.0000). ChatGPT-3.5 was misleading in 5 responses whereas ChatGPT-4.0 was misleading in 3 (31.3% vs 18.75%, P = .6851). ChatGPT-3.5 had quality resources in 10 responses whereas ChatGPT-4.0 had quality resources in 16 (62.5% vs 100%, P = .0177). AAO-HNS CPG FRES (62.4 ± 16.6) demonstrated an appropriate readability score of at least 60, while both ChatGPT-3.5 (39.1 ± 7.3) and 4.0 (42.8 ± 8.5) failed to meet this standard. All platforms had FKGL means that exceeded the recommended level of 6 or lower. Conclusion: While ChatGPT-4.0 had significantly better resource reporting, both models have room for improvement in being more comprehensive, more readable, and less misleading for patients.

The evolving landscape of glioblastoma stem cells.

PURPOSE OF REVIEW: Recent advances in the role of cancer stem cells (CSCs) in glioblastoma will be reviewed. RECENT FINDINGS: In the decade since the description of brain tumor CSCs, the potential significance of these cells in tumor growth, therapeutic resistance, and spread has become evident. Most recently, the interplay between CSCs, tumor genetics, and the microenvironment has offered potential nodes of fragility under therapeutic development. The CSC phenotype is informed by specific receptor signaling, and study of the regulation of stem cell genes by transcription factors and microRNAs has identified a number of new targets amenable to treatment. Like normal stem cells, CSCs display specific epigenetic landscapes and metabolic profiles. SUMMARY: Brain cancers activate core stem cell regulatory pathways to empower self-renewal, maintenance of an organ system (albeit an aberrant one), and survival under stress that collectively permits tumor growth, therapeutic resistance, invasion, and angiogenesis. These properties have implicated CSCs as contributors in GBM progression and recurrence, spurring a search for anti-CSC therapies that do not disrupt normal stem cell maintenance. The last year has witnessed a rapid evolution in the understanding of CSC biology to inform preclinical targeting.

Tissue-engineered vocal fold replacement in swine: Methods for functional and structural analysis.

We have developed a cell-based outer vocal fold replacement (COVR) as a potential therapy to improve voice quality after vocal fold (VF) injury, radiation, or tumor resection. The COVR consists of multipotent human adipose-derived stem cells (hASC) embedded within a three-dimensional fibrin scaffold that resembles vocal fold epithelium and lamina propria layers. Previous work has shown improved wound healing in rabbit studies. In this pilot study in pigs, we sought to develop methods for large animal implantation and phonatory assessment. Feasibility, safety, and structural and functional outcomes of the COVR implant are described. Of eight pigs studied, six animals underwent COVR implantation with harvest between 2 weeks and 6 months. Recovery of laryngeal tissue structure was assessed by vibratory and histologic analyses. Recovery of voice function was assessed by investigating acoustic parameters that were derived specifically for pigs. Results showed improved lamina propria qualities relative to an injured control animal at 6 months. Acoustic parameters reflected voice worsening immediately after surgery as expected; acoustics displayed clear voice recovery in the animal followed for 6 months after COVR. These methods form the basis for a larger-scale long-term pre-clinical safety and efficacy study.

Microbial Changes Associated With Oral Cavity Cancer Progression.

OBJECTIVE: To examine the oral microbiome in the context of oral cavity squamous cell carcinoma. STUDY DESIGN: Basic science research. SETTING: Academic medical center. METHODS: Oral swabs were collected from patients presenting to the operating room for management of oral cavity squamous cell carcinoma and from age- and sex-matched control patients receiving surgery for unrelated benign conditions. 16S ribosomal RNA (rRNA) sequencing was performed on genetic material obtained from swabs. A bacterial rRNA gene library was created and sequence reads were sorted into taxonomic units. RESULTS: Thirty-one control patients (17 males) and 35 cancer patients (21 males) were enrolled. Ages ranged from 23 to 89 (median 63) for control patients and 35 to 86 (median 66) for cancer patients. Sixty-one percent of control patients and 63% of cancer patients were smokers. 16S analyses demonstrated a significant decrease in Streptococcus genera in oral cancer patients (34.11% vs 21.74% of the population, p = .04). Increases in Fusobacterium, Peptostreptococcus, Parvimonas, and Neisseria were also found. The abundance of these bacteria correlated with tumor T-stage. CONCLUSION: 16S rRNA sequencing demonstrated changes in bacterial populations in oral cavity cancer and its progression compared to noncancer controls. We found increases in bacteria genera that correspond with tumor stage-Fusobacteria, Peptostreptococcus, Parvimonas, Neisseria, and Treponema. These data suggest that oral cancer creates an environment to facilitate foreign bacterial growth, rather than implicating a specific bacterial species in carcinogenesis. These bacteria can be employed as a potential marker for tumor progression or interrogated to better characterize the tumor microenvironment.

A randomized comparison of ultrathin and standard colonoscope in cecal intubation rate and patient tolerance.

BACKGROUND: Complete colonoscopy examination cannot be performed in as many as 10% of cases. The new 9.2-mm ultrathin colonoscope (UTC) with an extra bending section may improve procedure tolerance and allow improvement in colonoscopy completion rate compared with a 12.9-mm standard colonoscope (SC). OBJECTIVE: To compare the performance of the 9.2-mm UTC with that of the 12.9-mm SC. DESIGN: Prospective, randomized, controlled trial. SETTING: Academic endoscopic unit. PATIENTS: Subjects 18 years and older undergoing their first colonoscopy. INTERVENTION: Subjects were randomized to either the UTC or SC group. MAIN OUTCOME MEASUREMENTS: First and rescue successful cecal intubation rates, subject satisfaction scores, and sedation requirements were compared. RESULTS: A total of 1121 patients (56% women, mean age 53.6 years) were randomized to the UTC group (n = 551) or the SC group (n = 570). There was no statistically significant difference in the first successful cecal intubation rate between the UTC and SC groups (98.9% vs 97.4%, P = .057). The mean (standard deviation) dose of midazolam and pethidine used was significantly lower in the UTC group (2.65 [0.65] mg vs 2.82 [0.85] mg, P < .001 and 27.6 [7.4] mg vs 29.7 [9.6] mg, P < .001, respectively). The mean (standard deviation) patient satisfaction score was similar between groups (6.99 [2.89] vs 7.04 [3.06], P = .762). Of the 21 patients (1.9%) with an incomplete initial colonoscopy (6 in the UTC group and 15 in the SC group), all 6 in the UTC group had their procedure completed with an SC. Eleven of 15 patients in the SC group had their procedures completed with a UTC in the same session. LIMITATIONS: Low failure rate may mask any difference between the 2 colonoscopes as a rescue instrument. CONCLUSIONS: The 9.2-mm UTC has performance characteristics similar to those of an SC in Chinese subjects undergoing their first colonoscopy performed by experienced and trainee endoscopists. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01142167.).

Vocal Fold Cyst Formation after Photoangiolytic KTP Laser Treatment of Early Glottic Cancer.

OBJECTIVE: The incidence of post-operative glottic cyst (POGC) formation in patients treated with transoral laser microsurgery with potassium-titanyl-phosphate laser (TLM-KTP) photoablation of early glottic carcinoma (EGC) has not previously been described. METHODS: A retrospective chart review was performed to identify all patients with early glottic cancer who underwent with single-modality TLM-KTP at our institution. Each patient received regular follow up with videostroboscopy for tumor surveillance. New glottic cysts seen on surveillance examinations were noted and their management was documented. RESULTS: A total of 33 patients met inclusion criteria. Eight patients (24%) developed POGC's within the original geographic perimeter of the cancerous vocal fold(s): 6 in the infraglottic region and 2 near the vocal process, at an average of 8 months after their initial cancer surgery. Of these 8 POGC's, 7 were at the periphery of the original tumor distribution and 1 was in the center of it. No POGC's were associated with any change in voice. Four of the 8 POGC's were phonosurgically excised, all without evidence of malignancy on pathology. The remaining 4 were monitored: 2 were stable for an average of 49 months of follow up; the remaining 2 resolved spontaneously by 7 and 31 months after first identification. CONCLUSIONS: POGC's are a frequent sequela of TLM-KTP for EGC. While these results suggest that they are unlikely to represent submucosal recurrences, surgeons should have a low threshold to biopsy if there is clinical concern for such and should counsel patients pre-operatively about the potential for their formation.

Large tracheoesophageal granular cell tumor: An atypical case presentation, location, and management.

INTRODUCTION: Granular cell tumors (GCT) are rare tumors that most frequently present in the oral cavity. While some present within the gastrointestinal tract, a GCT near the trachea is an extremely rare occurence. PRESENTATION OF CASE: A 42-year-old man presented to the Emergency Department after a motor vehicle accident. A computerized tomography (CT) scan revealed an incidental soft tissue 3.2 × 5.5 cm mass anterior to the esophagus and posterior to the trachea with no adjacent lymphadenopathy. The patient denied dyspnea, voice changes, or dysphagia. Due to its size and location, the patient underwent a transcervical excision of the retrotracheal tumor. Tumor cells were positive for CD68, CD163, S100, and SOX10, confirming a GCT. CONCLUSION: This is a distinctive presentation of a large (5 cm) GCT in the plane between the trachea and esophagus. GCTs are not often on the differential diagnosis of masses that present in this region.

Laryngeal Manifestations of Ehlers-Danlos Syndrome.

OBJECTIVES: The identification of voice and airway manifestations of Ehlers-Danlos Syndrome (EDS), diagnoses, and potential treatment modalities. STUDY DESIGN: Single institution retrospective case series. METHODS: We examined all patients presenting to our institution over a span of 10 years with a history of EDS or who were subsequently diagnosed with EDS after their evaluation. Demographic and clinical data were collected. RESULTS: Four patients were identified with an underlying diagnosis of EDS. All four patients were heavy voice users. All four patients had history and/or stroboscopy findings suggesting vocal hyperfunction, which we suspect is due to EDS-related hypermobility of the cricoarytenoid joint or fragility of the superficial lamina propria. Two patients also had respiratory symptoms - one with respiratory muscle weakness and sensation loss and one with inducible laryngeal obstruction. All patients were treated with voice therapy with subsequent improvement in their symptoms. CONCLUSIONS: Patients with EDS may present to laryngology clinics with symptoms of dysphonia or dyspnea secondary to their underlying condition. Voice therapy is a low-risk and potentially beneficial treatment in this patient population.

Measuring SARS-CoV-2 aerosolization in rooms of hospitalized patients.

Objective: Airborne spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a significant risk for healthcare workers. Understanding transmission of SARS-CoV-2 in the hospital could help minimize nosocomial infection. The objective of this pilot study was to measure aerosolization of SARS-CoV-2 in the hospital rooms of COVID-19 patients. Methods: Two air samplers (Inspirotec) were placed 1 and 4 m away from adults with SARS-CoV-2 infection hospitalized at an urban, academic tertiary care center from June to October 2020. Airborne SARS-CoV-2 concentration was measured by quantitative reverse transcription polymerase chain reaction and analyzed by clinical parameters and patient demographics. Results: Thirteen patients with COVID-19 (eight females [61.5%], median age: 57 years old, range 25-82) presented with shortness of breath (100%), cough (38.5%) and fever (15.4%). Respiratory therapy during air sampling varied: mechanical ventilation via endotracheal tube (n = 3), high flow nasal cannula (n = 4), nasal cannula (n = 4), respiratory helmet (n = 1), and room air (n = 1). SARS-CoV-2 RNA was identified in rooms of three out of three intubated patients compared with one out of 10 of the non-intubated patients (p = .014). Airborne SARS-CoV-2 tended to decrease with distance (1 vs. 4 m) in rooms of intubated patients. Conclusions: Hospital rooms of intubated patients had higher levels of aerosolized SARS-CoV-2, consistent with increased aerosolization of virus in patients with severe disease or treatment with positive pressure ventilation through an endotracheal tube. While preliminary, these data have safety implications for health care workers and design of protective measures in the hospital. Level of Evidence: 2.

Durability of peginterferon alfa-2b treatment at 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B.

UNLABELLED: Approximately 30%-40% of patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with peginterferon and/or lamivudine achieve HBeAg seroconversion 6 months after the end of treatment. The durability and long-term effect of treatment are unknown. In this study, 85 HBeAg-positive patients who received peginterferon alfa-2b 1.5 microg/kg/week for 32 weeks and lamivudine 100 mg/day for 52 or 104 weeks were prospectively followed for 6.1 +/- 1.7 years posttreatment. Twenty-five (29%) patients had virologic response (HBeAg seroconversion and HBV DNA <10,000 copies/mL) at 5 years. The rate of HBeAg seroconversion rose progressively from 37% at the end of treatment to 60% at 5 years. Twenty-seven (32%) and 11 (13%) patients had undetectable HBV DNA (<100 copies/mL) at the end of peginterferon treatment and at 5 years, respectively. Two (2.4%) patients achieved hepatitis B surface antigen (HBsAg) seroclearance at 2.6 and 84 months posttreatment. Among virologic responders at the end of treatment, 82% and 57% and sustained HBeAg seroconversion and virologic response at 5 years. End-of-treatment serum quantitative HBsAg was significantly lower in patients with sustained virologic response at 5 years (median 1,431 IU/mL versus 2,689 IU/mL [P = 0.041]). At the last follow-up, the liver stiffness measurement by transient elastography was 5.8 +/- 2.7 kPa. Only two patients had liver stiffness suggestive of advanced fibrosis. Week 16 HBV DNA, end-of-treatment HBeAg seroconversion, and undetectable HBV DNA were independent factors associated with virologic response at 5 years. The duration of concomitant lamivudine treatment had no impact on any long-term response. CONCLUSION: Peginterferon has high durability in HBeAg-positive chronic hepatitis B patients with end-of-treatment virologic response.

The effect of obesity on intrahepatic cytokine and chemokine expression in chronic hepatitis C infection.

BACKGROUND: Obese subjects with chronic hepatitis C virus (HCV) infection have more rapidly progressive liver disease. Objective In this study, we aimed to compare the hepatic cytokine and chemokine profiles in obese and lean subjects with chronic HCV infection using qRT-PCR and immunohistochemistry. METHODS: Liver biopsies from 55 subjects were studied, including 20 with chronic hepatitis C, 25 with non-alcoholic fatty liver disease and 10 subjects with non-diseased liver. RESULTS: Compared to the control groups, the liver injury in chronic hepatitis C was characterised by increased expression of several T-helper-1 cytokines including interferon-gamma and tumour necrosis factor-alpha, and chemokines such as RANTES, IP-10 and MCP-1. In particular, in comparison with lean (BMI or=30 kg/m(2)) HCV infected subjects had increased hepatic expression of interferon-gamma (p=0.004) and tumour necrosis factor-alpha (p<0.001), as well as increased expression of IP-10 (p=0.009) and MCP-1 (p<0.001). Localisation of these inflammatory chemokines revealed that in comparison to lean-HCV subjects, HCV infected liver from obese subjects exhibited significantly increased expression of IP-10 (p<0.001) and MCP-1 (p=0.02) in the inflammatory infiltrate of the portal tracts. In parallel, there was increased CD3 infiltration in the liver of obese-HCV subjects. CONCLUSIONS: The data provide important mechanistic information on the cause of hepatic injury in obese-HCV subjects including: (1) enhanced T helper-1 cytokine response patterns-to promote hepatocellular injury; (2) increased expression of the chemokines IP-10 and MCP-1 at both the mRNA and protein levels-to enhance inflammatory cell recruitment; (3) differing localisation of these chemokines within the liver of obese-HCV versus lean-HCV subjects-implying different inducing stimuli and; (4) increased CD3 expression in the liver of obese-HCV subjects-concordant with the increased expression of T cell chemoattractants.

Rate and factors affecting treatment uptake of patients with chronic hepatitis C in a tertiary referral hospital.

BACKGROUND: Contraindications to interferon and ribavirin for treatment of chronic hepatitis C (CHC) are well recognized, and previous data indicated the consequent suboptimal treatment uptake. AIM: To evaluate the treatment rate of CHC patients in a tertiary referral center in Hong Kong, and to examine the reasons for non-treatment. METHODS: A retrospective review of all referred CHC patients to the outpatient clinic was conducted. Treatment uptake rate was evaluated and patients' sociodemographic, biochemical, and histological data were examined to identify reasons for treatment decision. RESULTS: CHC patients (303) were assessed for antiviral therapy from 2000 to 2009. Of the patients, 138 (45.5%) did not receive antiviral therapy. Reasons for non-treatment were as follows: 31.9% declined treatment, 18.8% had decompensated cirrhosis, 12.3% were considered too elderly, 17.4% had too mild liver disease, 7.2% had psychiatric history, 7.2% had significant comorbidities, and 2.9% had ongoing alcohol or substance abuse. Independent factors associated with non-treatment were older age (adjusted odds ratio [aOR] 1.05, 95% confidence interval [CI] 1.03-1.08, p < 0.001), significant comorbidities (aOR 2.53, 95% CI 1.34-4.78, p = 0.004), psychiatric history (aOR 6.04, 95% CI 2.14-17.02, p < 0.001), mild liver disease (aOR 7.72, 95% CI 3.86-15.44, p < 0.001) and decompensated cirrhosis (aOR 9.42, 95% CI 2.57-34.50, p < 0.001). CONCLUSIONS: Current treatment uptake for CHC patients was suboptimal, as a large proportion of patients were either reluctant for treatment or not suitable for the current antiviral therapy. Multidisciplinary interventions are needed in the short term while alternative antiviral therapy is desired in the long term to overcome barriers to treatment.

Atypical Laryngeal Infections: Localized Lesions from Unusual Organisms May Simulate Malignancy.

OBJECTIVE: The identification of rare sources of laryngeal infection in immunocompetent patients. Recovered organisms were Mycobacterium tuberculosis (laryngeal tuberculosis [LTB]), Mycobacterium fortuitum (laryngeal Mycobacterium fortuitum [LMF]), and Blastomyces dermatiditis (laryngeal blastomycosis [LB]). METHOD: Single institution retrospective case series of three patients over a 2.5-year period and review of the literature on laryngeal infections by three atypical organisms. RESULTS: Three patients presented with hoarseness and cough; one additionally had throat pain (LTB). Indirect laryngoscopy demonstrated diffuse laryngeal ulceration (LTB, LMF) and an exophytic, contiguous glottic mass (LB). Direct microlaryngoscopic biopsies and cultures established the diagnoses, including a frozen section in one case (LB), which prevented a simultaneously planned surgical resection. Appropriate antimicrobial therapy yielded dramatic laryngeal and corresponding vocal improvement, for which we provide unique photo and audio documentation. In the last 10 years, fewer than 500 cases of LTB have been reported in the English language medical literature, principally outside the United States. To date, there have been reports of only 34 LB and no cases of LMF. CONCLUSION: Atypical infections of the larynx may be localized and mimic laryngeal cancer on endoscopy. Tissue examination as well as microbiologic samples are diagnostic and complementary.

Molecular biology of oral cavity squamous cell carcinoma.

Oral cavity squamous cell carcinoma (OCSCC) is a heterogeneous and complex disease that arises due to dysfunction of multiple molecular signaling pathways. Recent advances in high-throughput genetic sequencing technologies coupled with innovative analytical techniques have begun to characterize the molecular determinants driving OCSCC. An understanding of the key molecular signaling networks underlying the initiation and progression of is essential for informing treatment of the disease. In this chapter, we discuss recent findings of key genes altered in OCSCC and potential treatments targeting these genes.