Evaluation of subarcuate canal on CT images in the perspective of clinical basis.

OBJECTIVES: The aim of our study to contribute to the field of morphometrics by including measurements of the SAC and SAF and their distances from surrounding structures, particularly for surgeons involved in retrosigmoid approach for internal acoustic meatus tumor surgery and cerebellopontine angle surgery. Although there is limited information in the literature regarding the role of the subarcuate fossa (SAF) and subarcuate canal (SAC), it has been suggested that the SAC may be a potential pathway for infection from the middle ear to the posterior cranial fossa, and cerebellar abscesses may have this origin. METHODS: For the images of our study, computerized tomography images of 118 individuals (59 females and 59 males) between the ages of 18-65 who applied to Bayindir Health Group. RESULTS: The width of the cranial opening of the subarcuate canal was determined as 44 ± 0.54 mm, width of the labyrinth opening of the subarcuate canal was determined as 60 ± 0.42 mm, Length of the subarcuate canal was determined as 8.79 ± 2.31 mm, width of the subarcuate canal was determined as 5.54 ± 1.75 mm, and depth of subarcuate fossa was determined as 1.67 ± 0.69 mm. The distance of the cranial opening of the subarcuate canal to the superior semicircular canal (SSC-SAC/C) was measured as 5.33 ± 1.81 mm, The distance of the labyrinth opening of the subarcuate canal to the superior semicircular canal (SSC-SAC/L) was measured as 3.90 ± .98 mm, length of the petrous part of the temporal bone medial to the anterior semicircular canal measured from the apex to the SSCD (PLM) was measured as 33.56 ± 0.42 mm. No statistically significant differences were found between the right and left sides. CONCLUSIONS: The morphometric measurements obtained in this study can provide useful information for neurosurgeons, neurotologist and otolaryngologists involved in retrosigmoid approach for internal acoustic meatus tumor surgery and cerebellopontine angle surgery, and for patients undergoing cochlear implant planning with a retrofacial approach.

A Single-Step Immunocapture Assay to Quantify HCC Exosomes Using the Highly Sensitive Fluorescence Nanoparticle-Tracking Analysis.

Introduction: Extracellular vesicles could serve as a non-invasive biomarker for early cancer detection. However, limited methods to quantitate cancer-derived vesicles in the native state remain a significant barrier to clinical translation. Aim: This research aims to develop a rapid, one-step immunoaffinity approach to quantify HCC exosomes directly from a small serum volume. Methods: HCC-derived exosomes in the serum were captured using fluorescent phycoerythrin (PE)-conjugated antibodies targeted to GPC3 and alpha-fetoprotein (AFP). Total and HCC-specific exosomes were then quantified in culture supernatant or patient-derived serums using fluorescence nanoparticle tracking analysis (F-NTA). The performance of HCC exosome quantification in the serum was compared with the tumor size determined by MRI. Results: Initially we tested the detection limits of the F-NTA using synthetic fluorescent and non-fluorescent beads. The assay showed an acceptable sensitivity with a detection range of 104-108 particles/mL. Additionally, the combination of immunocapture followed by size-exclusion column purification allows the isolation of smaller-size EVs and quantification by F-NTA. Our assay demonstrated that HCC cell culture releases a significantly higher quantity of GPC3 or GPC3+AFP positive EVs (100-200 particles/cell) compared to non-HCC culture (10-40 particles/cell) (p<0.01 and p<0.05 respectively). The F-NTA enables absolute counting of HCC-specific exosomes in the clinical samples with preserved biological immunoreactivity. The performance of F-NTA was clinically validated in serum from patients ± cirrhosis and with confirmed HCC. F-NTA quantification data show selective enrichment of AFP and GPC3 positive EVs in HCC serum compared to malignancy-free cirrhosis (AUC values for GPC3, AFP, and GPC3/AFP were found 0.79, 0.71, and 0.72 respectively). The MRI-confirmed patient cohort indicated that there was a positive correlation between total tumor size and GPC3-positive exosome concentration (r:0.78 and p<0.001). Conclusion: We developed an immunocapture assay that can be used for simultaneous isolation and quantification of HCC-derived exosomes from a small serum volume with high accuracy.

The number of hepatocellular carcinoma foci as predictor of poor response to tumor-directed therapies in patients awaiting liver transplantation: a prospective cohort study.

BACKGROUND AND AIMS: Tumor-directed therapies (TDTs) are a constitutive part of hepatocellular carcinoma (HCC) treatment in patients awaiting liver transplantation (LT). While most patients benefit from TDTs as a bridge to LT, some patients drop out from the waiting list due to tumor progression. The study aimed to determine the risk factors for poor treatment outcome following TDTs among patients with HCC awaiting LT. METHODS: A total of 123 patients with HCC were evaluated with 92 patients meeting Milan Criteria enrolled in the prospective cohort study. Tumor response was evaluated using the modified Response Evaluation Criteria for Solid Tumors for HCC 1 month after the procedure. The risk factors for progressive disease (PD) and dropout were evaluated. RESULTS: After TDT, 55 patients (59.8%) achieved complete or partial response (44.6% and 15.2% respectively), 17 patients (18.5%) had stable disease, and 20 patients (21.7%) were assessed as PD. Multivariate analysis revealed a significant and independent association between the number of HCC foci and PD ( P  = 0.03, OR = 2.68). There was no statistically significant association between treatment response and demographics, MELDNa score, pre-and post-treatment alpha-fetoprotein (AFP), cumulative tumor burden the largest tumor size, or TDT modality. PD was the major cause of dropout in our cohort. Pre-treatment AFP levels ≥200 ng/ml had a strong association with dropout after TDTs ( P  = 0.0005). CONCLUSION: This study demonstrated the presence of multifocal HCC is the sole prognostic factor for PD following TDTs in HCC patients awaiting LT. We recommend prioritizing patients with multifocal HCC within Milan criteria by exception points for LT to improve the dropout rate.

Change of frontal sinus in age of according to the international frontal sinus anatomy classification.

BACKGROUND: The radiological and surgical anatomy of the frontal sinus should be well-known in all age groups to successfully manage frontal sinus diseases and reduce the risk of complications in sinus surgery. PURPOSE: To define frontal sinus and frontal cells according to the International Frontal Sinus Anatomy Classification (IFAC) criteria in pediatrics and adults. MATERIAL AND METHODS: A total of 320 frontal recess regions of 160 individuals (80 pediatric, 80 adults) who underwent a computed tomography (CT) scan of the paranasal sinus (PNS) were included in the study. Agger nasi cells, supra agger cells, supra agger frontal cells, suprabullar cells, suprabullar frontal cells, supraorbital ethmoid cells, and frontal septal cells were evaluated in the CT analysis. RESULTS: The incidence rates of the investigated cells were determined to be 93.1%, 41.9%, 60.0%, 76.3%, 58.5%, 18.8%, and 0% in the pediatric group, respectively, and 86.3%, 35.0%, 44.4%, 54.4%, 46.9%, 19.4%, and 3.4% in the adult group, respectively. Considering the unilateral and bilateral incidence of the cells, agger nasi cells were highly observed bilaterally in both the pediatric group (89.87%) and the adult group (86.48%). CONCLUSION: Our study results show that IFAC can be used as a guide to increase the chance of surgical treatment in the pediatric and adult groups and that the prevalence of frontal cells can be determined radiologically and contributes to the generation of estimations of the prevalence of frontal cells.

Targeting ER stress/PKA/GSK-3ß/ß-catenin pathway as a potential novel strategy for hepatitis C virus-infected patients.

BACKGROUND: Chronic hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC). The HCC risk, while decreased compared with active HCV infection, persists in HCV-cured patients by direct-acting antiviral agents (DAA). We previously demonstrated that Wnt/ß-catenin signaling remained activated after DAA-mediated HCV eradication. Developing therapeutic strategies to both eradicate HCV and reverse Wnt/ß-catenin signaling is needed. METHODS: Cell-based HCV long term infection was established. Chronically HCV infected cells were treated with DAA, protein kinase A (PKA) inhibitor H89 and endoplasmic reticulum (ER) stress inhibitor tauroursodeoxycholic acid (TUDCA). Western blotting analysis and fluorescence microscopy were performed to determine HCV levels and component levels involved in ER stress/PKA/glycogen synthase kinase-3ß (GSK-3ß)/ß-catenin pathway. Meanwhile, the effects of H89 and TUDCA were determined on HCV infection. RESULTS: Both chronic HCV infection and replicon-induced Wnt/ß-catenin signaling remained activated after HCV and replicon eradication by DAA. HCV infection activated PKA activity and PKA/GSK-3ß-mediated Wnt/ß-catenin signaling. Inhibition of PKA with H89 both repressed HCV and replicon replication and reversed PKA/GSK-3ß-mediated Wnt/ß-catenin signaling in both chronic HCV infection and replicon. Both chronic HCV infection and replicon induced ER stress. Inhibition of ER stress with TUDCA both repressed HCV and replicon replication and reversed ER stress/PKA/GSK-3ß-dependent Wnt/ß-catenin signaling. Inhibition of either PKA or ER stress both inhibited extracellular HCV infection. CONCLUSION: Targeting ER stress/PKA/GSK-3ß-dependent Wnt/ß-catenin signaling with PKA inhibitor could be a novel therapeutic strategy for HCV-infected patients to overcomes the issue of remaining activated Wnt/ß-catenin signaling by DAA treatment. Video Abstract.

Magnetic resonance arthrographic demonstration of extension of labral defects in paraglenoid labral cysts.

OBJECTIVE: This study aimed to investigate the extension of labral tears associated with paraglenoid labral cysts by magnetic resonance arthrography. METHODS: The magnetic resonance and magnetic resonance arthrography images of patients with paraglenoid labral cysts who presented to our clinic between 2016 and 2018 were examined. In patients with paraglenoid labral cysts, the location of the cysts, the relation between the cyst and the labrum, the location and extent of glenoid labrum damage, and whether there was contrast medium passage into the cysts were investigated. The accuracy of magnetic resonance arthrographic information was evaluated in patients undergoing arthroscopy. RESULTS: In this prospective study, a paraglenoid labral cyst was detected in 20 patients. In 16 patients, there was a defect in the labrum adjacent to the cyst. Seven of these cysts were adjacent to the posterior superior labrum. In 13 patients, there were contrast solution leak into the cyst. For the remaining seven patients, no contrast-medium passage was observed in the cyst. Three patients had sublabral recess anomalies. Two patients had rotator cuff muscle denervation atrophy accompanying the cysts. The cysts of these patients were larger compared to those of the other patients. CONCLUSION: Paraglenoid labral cysts are frequently associated with the rupture of the adjacent labrum. In these patients, symptoms are generally accompanied by secondary labral pathologies. Magnetic resonance arthrography can be successfully used not only to demonstrate the association of the cyst with the joint capsule and labrum, but also to reliably demonstrate the presence and extension of labral defects.

Detection of the glenoid bare spot by non-arthrographic MR imaging, conventional MR arthrography, and 3D high-resolution T1-weighted VIBE MR arthrography: comparison with CT arthrography.

OBJECTIVES: To determine the diagnostic accuracy of non-arthrographic MR imaging, conventional MR arthrography, and 3D T1-weighted volumetric interpolated breath-hold examination (VIBE) MR arthrography sequences as compared with a CT arthrography in the diagnosis of glenoid bare spot. METHODS: A retrospective study of 216 patients who underwent non-arthrographic MR imaging, conventional MR arthrography, VIBE MRI arthrography, and CT arthrogram between January 2011 and March 2022 was conducted. The diagnostic accuracy of non-arthrographic MR imaging, direct MR arthrography, and VIBE MRI arthrography in the detection of glenoid bare spot was compared with that of CT arthrography. All studies were reviewed by 2 MSK radiologists. Interobserver agreement for MR imaging and MR arthrographic findings was calculated. RESULTS: Sixteen of 216 patients were excluded. Twenty-three of 200 shoulders had glenoid bare spot on CT arthrographic images. The glenoid bare spot was detected in 11 (47.8%) and 7 (30.4%) patients on conventional non-arthrographic MR images and in 18 (78.3%) and 16 (69.6%) patients on conventional MR arthrograms by observers 1 and 2, respectively. Both observers separately described the bare spot in 22 of 23 patients (95.7%) on 3D volumetric MR arthrograms. Interobserver variabilities were fair agreement for conventional non-arthrographic MR imaging (κ = 0.35, p < 0.05), moderate agreement for conventional MR arthrogram (κ = 0.50, p < 0.05), and near-perfect agreement for 3D volumetric MR arthrogram reading (κ = 0.87, p < 0.05). CONCLUSIONS: A 3D high-resolution T1-weighted VIBE MR arthrography sequence may yield diagnostic performance that is comparable with that of CT arthrography in the diagnosis of glenoid bare spot. KEY POINTS: •Glenoid bare spot should not be misdiagnosed as a transchondral defect of the glenoid surface by radiologists. •A 3D high-resolution T1-weighted VIBE MR arthrography sequence may be used as a high-sensitivity imaging technique in the diagnosis of glenoid bare spot.

Pathogenesis and Mechanisms of SARS-CoV-2 Infection in the Intestine, Liver, and Pancreas.

The novel coronavirus, SARS-CoV-2, rapidly spread worldwide, causing an ongoing global pandemic. While the respiratory system is the most common site of infection, a significant number of reported cases indicate gastrointestinal (GI) involvement. GI symptoms include anorexia, abdominal pain, nausea, vomiting, and diarrhea. Although the mechanisms of GI pathogenesis are still being examined, viral components isolated from stool samples of infected patients suggest a potential fecal-oral transmission route. In addition, viral RNA has been detected in blood samples of infected patients, making hematologic dissemination of the virus a proposed route for GI involvement. Angiotensin-converting enzyme 2 (ACE2) receptors serve as the cellular entry mechanism for the virus, and these receptors are particularly abundant throughout the GI tract, making the intestine, liver, and pancreas potential extrapulmonary sites for infection and reservoirs sites for developing mutations and new variants that contribute to the uncontrolled spread of the disease and resistance to treatments. This transmission mechanism and the dysregulation of the immune system play a significant role in the profound inflammatory and coagulative cascades that contribute to the increased severity and risk of death in several COVID-19 patients. This article reviews various potential mechanisms of gastrointestinal, liver, and pancreatic injury.

Magnetic resonance arthrographic demonstration of extension of labral defects in paraglenoid labral cysts

SUMMARY OBJECTIVE: This study aimed to investigate the extension of labral tears associated with paraglenoid labral cysts by magnetic resonance arthrography. METHODS: The magnetic resonance and magnetic resonance arthrography images of patients with paraglenoid labral cysts who presented to our clinic between 2016 and 2018 were examined. In patients with paraglenoid labral cysts, the location of the cysts, the relation between the cyst and the labrum, the location and extent of glenoid labrum damage, and whether there was contrast medium passage into the cysts were investigated. The accuracy of magnetic resonance arthrographic information was evaluated in patients undergoing arthroscopy. RESULTS: In this prospective study, a paraglenoid labral cyst was detected in 20 patients. In 16 patients, there was a defect in the labrum adjacent to the cyst. Seven of these cysts were adjacent to the posterior superior labrum. In 13 patients, there were contrast solution leak into the cyst. For the remaining seven patients, no contrast-medium passage was observed in the cyst. Three patients had sublabral recess anomalies. Two patients had rotator cuff muscle denervation atrophy accompanying the cysts. The cysts of these patients were larger compared to those of the other patients. CONCLUSION: Paraglenoid labral cysts are frequently associated with the rupture of the adjacent labrum. In these patients, symptoms are generally accompanied by secondary labral pathologies. Magnetic resonance arthrography can be successfully used not only to demonstrate the association of the cyst with the joint capsule and labrum, but also to reliably demonstrate the presence and extension of labral defects.

Case Report of a Patient With Posttraumatic Perilymphatic Fistula.

On a perilymphatic fistula, there is an extravasation of the perilymph fluid into the middle ear cavity. Cross-sectional imaging techniques have very important role in evaluation of inner and middle ear structures and temporal bone. While thin section CT scans can show successfully pneumolabyrinth and temporal bone fracture, high-resolution 3D volumetric MRI sequences can help to demonstrate posttraumatic ear effusion and cerebrospinal fluid fistula into inner ear or middle ear.

The effect of sarcopenia and serum myokines on prognosis and survival in cirrhotic patients: a multicenter cross-sectional study.

OBJECTIVE: Sarcopenia is one of the most significant contributors to morbidity in patients with chronic liver disease. Serum myokines are potential biomarkers for detecting early sarcopenia. We aimed to investigate the relationship between serum myokines and cirrhosis-related mortality in the early stages of the disease. METHODS: In total, 262 patients and 50 healthy controls were enrolled in this study, which was designed as a multicenter cross-sectional study. At the beginning of the study, sarcopenia was defined by computed tomography scans using the third lumbar vertebra skeletal muscle index. Serum myostatin, irisin, and follistatin levels, nutritional status of the patients, and muscle strength as measured by the handgrip test were recorded. Cirrhosis-related mortality and overall survival were evaluated in the fourth year of the study as the second checkpoint of cross-sectional analysis. RESULTS: A total of 145 (55.3%) patients were diagnosed with sarcopenia. Multivariate analysis revealed that low BMI, high levels of myostatin, and decreased irisin levels were independent predictors of sarcopenia. While serum irisin level was the most predictive parameter in terms of 4th-year cirrhosis-related mortality in the CHILD A group, serum myostatin levels were found more indicative in the CHILD BC group regardless of sarcopenia status ( P < 0.001). CONCLUSION: Serum myostatin levels predict sarcopenia in all stages of cirrhosis. Serum irisin levels can also be used as a potential biomarker to predict both treatable sarcopenia and cirrhosis-related mortality in CHILD A patients.

Impaired Autophagy Response in Hepatocellular Carcinomas Enriches Glypican-3 in Exosomes, Not in the Microvesicles.

Background and Aim: HCC development in liver cirrhosis is associated with impaired autophagy leading to increased production of extracellular vesicles (EVs) including exosomes and microvesicles. The goal of the study is to determine which of these particles is primarily involved in releasing of HCC-specific biomarker glypican-3 (GPC3) when autophagy is impaired. Methods: Streptavidin-coated magnetic beads were coupled with either biotinylated CD63 or Annexin A1 antibodies. Coupled beads were incubated with EVs isolated from either HCC culture or serum. EVs captured by immuno-magnetic beads were then stained with FITC or PE fluorescent-conjugated antibodies targeting exosomes (CD81), and microvesicles (ARF6). The percentage of GPC3 enrichment in the microvesicles and exosomes was quantified by flow cytometry. The impact of autophagy modulation on GPC3 enrichment in exosomes and microvesicles was assessed by treating cells with Torin 1 and Bafilomycin A1. For clinical validation, GPC3 content was quantified in microvesicles, and exosomes were isolated from the serum of patients with a recent HCC diagnosis. Results: The immune-magnetic bead assay distinguishes membrane-derived microvesicles from endosome-derived exosomes. The GPC3 expression was only seen in the CD63 beads group but not in the Annexin A1 beads group, confirming that in HCC, GPC3 is preferentially released through exosomes. Furthermore, we found that autophagy induction by Torin1 decreased GPC3-positive exosome secretion and decreased microvesicle release. Conversely, autophagy inhibition by Bafilomycin A1 increased the secretion of GPC3-positive exosomes. Serum analysis showed CD81+ve EVs were detected in exosomes and ARF6+ve vesicles were detected in microvesicles, suggesting that immunoaffinity assay is specific. The exosomal GPC3 enrichment was confirmed in isolated EVs from the serum of patients with HCC. The frequency of GPC3-positive exosomes was higher in patients with HCC (12.4%) compared to exosomes isolated from non-cirrhotic and healthy controls (3.7% and 1.3% respectively, p<0.001). Conclusion: Our results show that GPC3 is enriched in the endolysosomal compartment and released in exosome fractions when autophagy is impaired.