Circulating tumor HPV DNA in the management of HPV+ oropharyngeal cancer and its correlation with MRI.

BACKGROUND: First aim was to compare ddPCR assays of ctHPVDNA with p16 IHC and qualitative HPV PCR. Second aim was to carry out longitudinal blood sampling to test for association of ctHPVDNA with histological confirmed recurrence. Third aim was to perform a multidimensional assessment which included: (1) clinical features; (2) ctHPVDNA; (3) MRI-based tumor size measurements of primary tumor (PT) and cervical lymph node metastases (CLNM). METHODS: Plasma samples were collected before treatment and during follow-up, and ddPCR assay comprising E6 of HPV16 and HPV 33 and HPV 35 was used. RESULTS: Present study was conducted at diagnosis in 117 patients and revealed a ctHPVDNA sensitivity of 100% (95% CI 95.5-100) and a specificity of 94.4 (95% CI 81.3-99.3), positive predictive value (PPV) of 94.4 (95% CI 81.3-99.3), and negative predictive value (NPP) of 100% (95% CI 89.7-100). During follow-up ctHPVDNA had a sensitivity of 100% (95% CI 72.1-100)% and specificity of 98.4% (95% CI 91.7-100)%, PPV% of 90.9% (95% CI 62.3-98.4) and NPV% of 100% (95% CI 94.3-100) for ability to detect recurrence. Correlation between both the CLNM volume and the sum of PT and CLNM volume was observed. CONCLUSIONS: ctHPVDNA was superior to p16 in identification of HPV-OPSCC at diagnosis. Introduction of ctHPVDNA, beyond diagnostic setting, represents a great opportunity to improve follow-up protocol of OPSCC patients.

Occult femoral fracture: be aware of dual energy computed tomography.

A 74-year-old man was admitted to our emergency department following minor trauma. Plain radiographs and standard computed tomography (CT) scans revealed no signs of fractures. Subsequently, virtual noncalcium (VNCa) images were reconstructed, showing a linear area of bone marrow edema (BME) resembling a femoral neck fracture. Magnetic resonance imaging (MRI) was performed to confirm the presence of BME and an associated intraspongious fracture. In an emergency setting, dual-energy CT (DECT) and VNCa images can successfully identify occult femoral fractures, especially in patients with mild symptoms and minor trauma, thereby preventing misdiagnosis.

Peri-gastric appendagitis with lesser omentum hemorrhagic infarction: US, CT, and MRI findings of a rare entity.

Peri-gastric appendagitis followed associated with gastro-hepatic ligament/lesser omentum hemorrhagic infarction has not been well investigated yet. With an accurate radiological diagnosis of peri-gastric appendagitis, even in case of hemorrhagic infarction, the patient can receive supportive measures for the self-limited pain and can forgo surgery, endoscopy, and further invasive testing.

Myopericytoma: a rare case of parapharyngeal localization.

This case study presents a 66-year-old man referred to the Otolaryngology and Head and Neck Surgery department due to a one-history of persistent pain in the left posterior cervical region. No abnormalities were detected in the oral and pharyngeal regions during clinical and endoscopic examinations. Subsequently, a magnetic resonance imaging revealed a lesion (14 × 12 × 14 mm) into the left parapharyngeal space, with high signal intensity on T2-weighted images, enhancement after contrast medium, restricted signal on diffusion weighted imaging and high vascularization on perfusion MRI. The histological examination of the lesion led to a diagnosis of myopericitoma. Post-surgery, no adjuvant therapy was administered. Myopericytomas are rare soft-tissue benign neoplasms, predominantly reported in extremities, with a limited number of cases in the head and neck region and almost never described in the literature with elective localization in the parapharyngeal space.

Pneumonia Frequency and Severity in Patients With Symptomatic COVID-19: Impact of mRNA and Adenovirus Vector Vaccines.

BACKGROUND. Additional evidence of the role of COVID-19 vaccination in reducing pneumonia frequency and severity in the setting of breakthrough infection could help combat ongoing vaccine hesitancy. OBJECTIVE. The purpose of this article was to compare the frequency and severity of pneumonia on chest CT in patients with confirmed COVID-19 between patients who are unvaccinated and those who are fully vaccinated by messenger RNA (mRNA) or adenovirus vector vaccines. METHODS. This retrospective single-center study included 467 patients (250 men, 217 women; mean age, 65 ± 17 [SD] years) who underwent chest CT between December 15, 2021, and February 18, 2022, during hospitalization for symptomatic COVID-19, confirmed by reverse transcriptase-polymerase chain reaction assay. A total of 216 patients were unvaccinated, and 167 and 84 patients were fully vaccinated (defined as receipt of the second dose at least 14 days before COVID-19 diagnosis) by the BNT162b2 mRNA vaccine or the ChAdOx1-S adenovirus vector vaccine, respectively. Semiquantitative CT severity scores (CT-SS; 0-25 scale) were determined; CT-SS of 0 indicated absence of pneumonia. Presence of bilateral involvement was assessed in patients with pneumonia. Associations were explored between vaccination status and CT findings. RESULTS. The frequency of the absence of pneumonia was 15% (32/216) in unvaccinated patients, 29% (24/84) in patients fully vaccinated with ChAdOx1-S vaccine, and 51% (85/167) in patients fully vaccinated with BNT162b2 vaccine (unvaccinated and ChAdOx1-S vs BNT162b2: p < .001; unvaccinated vs ChAdOx1-S: p = .08). Mean CT-SS was significantly higher in unvaccinated patients (9.7 ± 6.1) than in patients fully vaccinated with BNT162b2 (5.2 ± 6.1) or ChAdOx1-S (6.2 ± 5.9) vaccine (both p < .001). Full vaccination was significantly associated with CT-SS independent of patient age and sex (estimate = -4.46; p < .001). Frequency of bilateral lung involvement was significantly higher in unvaccinated patients (158/184, 86%) and in patients fully vaccinated with ChAdOx1-S vaccine (54/60, 90%) than in patients fully vaccinated with BNT162b2 vaccine (47/82, 57%) (both p < .001). CONCLUSION. Pneumonia frequency and severity were lower in patients with full vaccination by mRNA and adenovirus vector vaccines who experienced breakthrough infections in comparison with unvaccinated patients. CLINICAL IMPACT. The visual observation by radiologic imaging of the protective effect of vaccination on lung injury in patients with breakthrough infections provides additional evidence supporting the clinical benefit of vaccination.

Unusual computed tomography findings of gas in the superior mesenteric artery system with no signs of porto-mesenteric venous gas in a case of acute mesenteric ischemia.

Acute Mesenteric Ischemia (AMI) is a rare life-threatening entity caused by sudden interruption of the blood supply to a segment of the bowel due to impairment of mesenteric arterial blood flow or venous drainage. Clinical presentation varies according to the time course of vascular occlusion. Contrast-enhanced Computed Tomography (CT) of the abdomen represents the main diagnostic test for AMI diagnosis, enabling fast and excellent evaluation of the intestine, mesenteric vasculature, and other ancillary characteristics of AMI. Typical CT findings of AMI include paralytic ileus, decreased or absent bowel wall contrast-enhancement, pneumatosis intestinalis, and porto-mesenteric venous gas. We hereby report a case of an 89-year-old man presenting with AMI due to Superior Mesenteric Artery (SMA) thrombotic occlusion following endovascular stenting superficial femoral arteries. Typical findings were observed on abdominal CT imaging, yet associated with the presence of gas exclusively in the SMA district, without any involvement of the porto-mesenteric venous system. Different imaging features and pitfalls can help radiologists to accurately diagnose AMI, especially when irreversible bowel damage is about to occur. Therefore, radiologists and emergency physicians should be aware of the unusual association between gas in the SMA arterial district and AMI, even in the absence of porto-mesenteric venous system involvement, in order to urge prompt surgical consultation when observed.

Molecular and histological traits of reduced lysosomal acid lipase activity in the fatty liver.

Recent studies demonstrated reduced blood lysosomal acid lipase (LAL) activity in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to verify hepatic LAL protein content and activity in in vitro and in vivo models of fat overload and in NAFLD patients. LAL protein content and activity were firstly evaluated in Huh7 cells exposed to high-glucose/high-lipid (HGHL) medium and in the liver of C57BL/6 mice fed with high-fat diet (HFD) for 4 and 8 months. LAL protein was also evaluated by immunohistochemistry in liver biopsies from 87 NAFLD patients and 10 controls, and correlated with hepatic histology. Huh7 cells treated with HGHL medium showed a significant reduction of LAL activity, which was consistent with reduced LAL protein levels by western blotting using an antibody towards the N-term of the enzyme. Conversely, antibodies towards the C-term of the enzyme evidenced LAL accumulation, suggesting a post-translational modification that masks the LAL N-term epitope and affects enzymatic activity. Indeed, we found a high rate of ubiquitination and extra-lysosomal localization of LAL protein in cells treated with HGHL medium. Consistent with these findings, inhibition of proteasome triggered dysfunctional LAL accumulation and affected LAL activity. Accumulation of ubiquitinated/dysfunctional LAL was also found in the liver of HFD fed mice. In NAFLD patients, hepatic levels of non-ubiquitinated/functional LAL were lower than in controls and inversely correlated with disease activity and some of the hallmarks of reduced LAL. Fat overload leads to LAL ubiquitination and impairs its function, possibly reducing hepatic fat disposal and promoting NAFLD activity.

An overview of deregulated lipid metabolism in nonalcoholic fatty liver disease with special focus on lysosomal acid lipase.

Obesity and type 2 diabetes are frequently complicated by excess fat accumulation in the liver, which is known as nonalcoholic fatty liver disease (NAFLD). In this context, liver steatosis develops as a result of the deregulation of pathways controlling de novo lipogenesis and fat catabolism. Recent evidences suggest the clinical relevance of a reduction in the activity of lysosomal acid lipase (LAL), which is a key enzyme for intracellular fat disposal, in patients with NAFLD. In this review, we provided a comprehensive overview of the critical steps in hepatic fat metabolism and alterations in these pathways in NAFLD, with a special focus on lipophagy and LAL activity. During NAFLD, hepatic fat metabolism is impaired at several levels, which is significantly contributed to by impaired lipophagy, in which reduced LAL activity may play an important role. For further research and intervention in NAFLD, targeting LAL activity may provide interesting perspectives.

Lipophagy Impairment Is Associated With Disease Progression in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries and is associated with aging and features of metabolic syndrome. Lipotoxicity and oxidative stress are consequent to dysregulation of lipid metabolism and lipid accumulation, leading to hepatocyte injury and inflammation. Lipophagy consists in selective degradation of intracellular lipid droplets by lysosome and mounting evidence suggests that lipophagy is dysregulated in NAFLD. Here we demonstrate lipophagy impairment in experimental models of NAFLD and in a NAFLD patient cohort by histomorphological and molecular analysis. High fat diet-fed C57BL/6J male mice and high-fat/high-glucose cultured Huh7 cells showed accumulation of both p62/SQSTM1 and LC3-II protein. In 59 NAFLD patients, lipid droplet-loaded lysosomes/lipolysosomes and p62/SQSTM1 clusters correlated with NAFLD activity score (NAS) and with NAS and fibrosis stage, respectively, and levels of expression of lysosomal genes, as well as autophagy-related genes, correlated with NAS and fibrosis stage. An increased amount of lipid droplets, lipolysosomes and autophagosomes was found in subjects with NAFLD compared to healthy subjects at ultrastructural level. In conclusion, here we observed that NAFLD is characterized by histological, ultrastructural and molecular features of altered autophagy that is associated with an impaired lipid degradation. Impaired autophagy is associated with features of advanced disease. Lipopolysosomes, as individuated with light microscopy, should be further assessed as markers of disease severity in NAFLD patients.

Long noncoding RNAs in nonalcoholic fatty liver disease and liver fibrosis: state-of-the-art and perspectives in diagnosis and treatment.

Nonalcoholic fatty liver disease (NAFLD) significantly impacts global health. Despite considerable research, its pathophysiology remains partially unclear. In addition, selective serum biomarkers of disease diagnosis and progression are missing. Long noncoding RNAs (lncRNAs) are a heterogeneous group of ncRNAs with crucial roles in biological processes underlying the pathophysiology of different human diseases. Recent studies have shown that lncRNA could be associated with the genesis and progression of NAFLD towards the most severe forms. Although the field is still in its infancy, it is tempting to speculate that these transcripts could be used as both diagnostic and therapeutic targets. In this review, we summarize recent findings on lncRNAs in the complex research field of NAFLD.