In Vitro Ballooned Hepatocytes Can Be Produced By Primary Human Hepatocytes and Hepatic Stellate Cell Sheets

Background Despite the increasing prevalence of Nonalcoholic steatohepatitis (NASH) worldwide, there is no effective treatment available for this disease. “Ballooned hepatocyte” is a characteristic finding in NASH and is correlated with disease prognosis, but their mechanisms of action are poorly understood; furthermore, neither animal nor in vitro models of NASH have been able to adequately represent ballooned hepatocytes. Herein, we engineered cell sheets to develop a new in vitro model of ballooned hepatocytes. Methods Primary human hepatocytes (PHH) and Hepatic stellate cells (HSC) were co-cultured to produce cell sheets, which were cultured in glucose and lipid containing medium, following which histological and functional analyses were performed. Results Histological findings showed hepatocyte ballooning, accumulation of fat droplets, abnormal cytokeratin arrangement, and the presence of Mallory-Denk bodies and abnormal organelles. These findings are similar to those of ballooned hepatocytes in human NASH. Functional analysis showed elevated levels of TGFβ-1, SHH, and p62, but not TNF-α, IL-8. Conclusions Exposure of PHH/HSC sheets to a glucolipotoxicity environment induces ballooned hepatocyte without inflammation. Moreover, fibrosis is an important mechanism underlying ballooned hepatocytes and could be the basis for the development of a new in vitro NASH model with ballooned hepatocytes.

Usefulness of ultrasonography for dynamic evaluation of medial meniscus hoop function in early knee osteoarthritis

This study aimed to evaluate the dynamics of the medial meniscus during knee flexion–extension by ultrasonography and compare them with MRI findings to confirm the usefulness of ultrasonography for evaluating early knee osteoarthritis (KOA). In total, 100 patients were diagnosed with early KOA using clinical and radiographical findings. Dynamic ultrasonographic evaluation and MRI were performed in all patients. Medial meniscal extrusion (MME) and medial meniscal tears were evaluated via ultrasonography and MRI. Abnormal MME was defined as MME > 2 mm on ultrasonography during knee extension. Patients with abnormal MME were divided into two groups: a decrease group (group D) and a non-decrease group (group N). Age, sex, absence or type of meniscus tear, and MME were compared between the two groups. Of the 100 patients, 75 demonstrated MME > 2 mm at knee extension. MME at all assessment positions using ultrasonography and MRI were significantly greater in group N (n = 34) than that in group D (n = 41). Medial meniscus posterior root tears or radial tears were observed in most cases in group N. A lack of decrease in MME from 0° to 90° of flexion on ultrasonography was a characteristic finding in patients with a loss of meniscal hoop function.

Etiology and Pathogenesis of Corticosteroid-Associated Osteonecrosis of the Femoral Head

Osteonecrosis of the femoral head (ONFH) is an intractable disease occurring at a relatively young age. The characteristic finding of ONFH – the femoral head collapse with severe hip pain – is observed in many cases, which frequently leads to further joint destruction, requiring surgical treatment. Among the associated factors of ONFH, majority of patients who require high-dose corticosteroid are still challenging due to inevitable therapeutic option regardless of poor prognosis. As a pathological mechanism, ONFH is defined as tissue necrosis in the femoral head region due to occlusion of the nutrient vessels; but the detailed micro-level processes leading to blood flow failure remains unclear. The elucidation of ONFH and the establishment of preventive therapy is desirable for these patients. Here, we discuss the etiology and pathogenesis of corticosteroid-associated ONFH by reviewing current literature.

Myopic Simple Hemorrhage Presenting as Radial Hemorrhage in Henle’s Fiber Layer

This case report describes a simple hemorrhage (SH) presenting as radial hemorrhage in Henle’s fiber layer (HFL) in a patient with high myopia. A 26-year-old girl with high myopia was referred to our center for sudden onset of decreased vision and a central scotoma in the right eye (OD). Best corrected visual acuity (BCVA) was 20/100 OD. Fundus examination showed a stellate intraretinal hemorrhage in the fovea of the OD. The hemorrhage was organized in a peculiar petaloid pattern with feathery distal edges, suggesting localization within the radially oriented HFL. The presence of both choroidal neovascularization and microvascular abnormalities consistent with macular telangiectasia type 2 (MacTel 2) were excluded. Based on these findings, a diagnosis of myopic SH was made. At 4-month follow-up BCVA OD spontaneously improved to 20/40, without any treatment been ever administered to the patient. Spectral-domain optical coherence tomography OD showed reabsorption of the hemorrhage and almost complete restoration of the foveal architecture. The intraretinal location and spread of the hemorrhage into the HFL in our patient are an unusual presentation of SH, which vividly highlights the anatomy of the fovea. Since fibers in HFL are quite delicate and loosely arranged, this layer is very susceptible to deposition of transudates, exudates, hemorrhage, and other products. Radial hemorrhage in HFL has been originally reported in 4 patients as complication of MacTel 2. It has been previously postulated that it may represent a characteristic finding in MacTel 2 that may develop as a result of microvascular abnormalities of the deep retinal capillary plexus. On the contrary, our data suggest that radial hemorrhage in the HFL does not represent a characteristic finding of MacTel 2, but must rather be considered a non-specific sign with multiple possible etiologies.

Podocytic Infolding Glomerulopathy in a Patient with Phospholipase A2 Receptor-Positive Membranous Nephropathy and Review of the Literature

Podocytic infolding glomerulopathy (PIG) is a rare diagnosis based on characteristic histopathologic findings on renal biopsy and was proposed as a new entity about a decade ago. It is a type of podocytic injury, characterized by invagination of the podocyte cell membrane (cytoplasmic projections from podocytes) into the glomerular basement membrane. The presence of microspheres and/or microtubules on electron microscopy is the characteristic finding. PIG is most often associated with autoimmune conditions like systemic lupus erythematosus. We report pathologic findings typical of PIG in a patient with phospholipase A2 receptor antibody-positive membranous nephropathy. She was treated with rituximab and responded well with decrease in proteinuria to the sub-nephrotic range.

Multi-modality imaging evaluation of the dorsal arachnoid web

Purpose Dorsal arachnoid web (DAW) is a rare intradural abnormality which is associated with progressive myelopathy. Our objective was to review multi-modality imaging techniques demonstrating the scalpel sign appearance in evaluation of DAW. Methods We retrospectively reviewed various imaging modalities of patients found to have DAW at our institution during January 2015 to February 2020. Five patients underwent surgical decompression with pathological correlation. The remaining patients were presumptively diagnosed based on the characteristic finding of scalpel sign. Clinical data were evaluated and correlated to imaging findings. All imaging modalities demonstrated the characteristic scalpel sign. Results Sixteen patients (10 females, and six males) with multi-imaging modalities were evaluated. Their mean age was 52 year (range 23–74 years). Fifteen patients underwent conventional spine MRI. Further high-resolution MR imaging techniques, e.g. 3D T2 myelographic sequence, were utilized with two patients. MRI spine CSF flow study was performed to evaluate the flow dynamic across the arachnoid web in one patient. Eight patients were evaluated with CT myelogram. Syrinx formation was discovered in seven (44%) patients; five (71%) of them underwent surgical resection and decompression. Two patients underwent successful catheter-directed fenestration of the web with clinical improvement. We found a statically significant positive correlation between the degree of cord displacement and compression with syrinx formation (r = 0.55 and 0.65 with p-value of 0.03 and 0.009, respectively). Conclusion DAW has characteristic scalpel sign independent of imaging modality. Multi-modality imaging evaluation of DAW is helpful for evaluation and surgical planning.

Vaping Induced Pathological Changes In The Lung Comparing With Imaging Finding-A Case Report Study

Vaping Associated Pulmonary Injury (VAPI) is a group of respiratory symptoms like shortness of breath and tachypnea and, oftentimes, it is associated with non-specific symptoms like generalized fatigue, body ache, fever, nausea, diarrhea, vomiting and chills. This entity has been previously categorized as a diagnosis of exclusion and best described as an exogenous lipoid pneumonia, or chemical pneumonitis. Exogenous lipoid pneumonia has characteristic finding in histology where inhaled fatty substances are recognized with special stain versus endogenous lipoid pneumonia, which is due to airway obstruction giving histology look of cholesterol crystals and accumulated debris. Here we describe the onset of an exogenous cause of lipoid pneumonia in an otherwise healthy patient using cannabis-containing products. We explore, similarities in the clinical case, identify common clinical features, characteristic radiologic findings along with cytological changes in the lungs.

Autofluorescence of choroidal vessels in Bietti’s crystalline dystrophy

ObjectiveTo describe the pattern of fundus autofluorescence (FAF) in Bietti’s crystalline dystrophy (BCD).Methods and analysisFrom the National Institutes of Health EyeGene database of 2769 patients with known pathogenic mutations, 5 patients with BCD-causing CYP4V2 mutations who had FAF images were selected. Demographic and genetic information and imaging files were obtained. From the FAF imaging files, unique autofluorescence (AF) patterns and correlation with retinal structures were assessed by three investigators for clinical significance.ResultsFive patients (four males, one female; mean age 56 years, range 42–76 years) were included, all with different CYP4V2 mutations. All patients displayed varying degrees of hypo-AF in the posterior pole. In four out of five patients, there was a relative hyper-AF of choroidal vessels within the hypo-AF area; this feature was limited to sclerotic vessels only. A transitional zone of speckled AF was visible around the hypo-AF area. This zone corresponded to the area containing retinal crystals on colour fundus photography; however, retinal crystals did not demonstrate hyper or hypo-AF.ConclusionsThis study presents a previously unreported characteristic finding in patients with BCD with CYP4V2 mutations. AF of choroidal vessels may aid in differentiating BCD from other retinal dystrophies.

A RARE CASE OF GENITAL POROKERATOSIS

Porokeratosis is a keratinization disorder of unknownetiology. It is characterized by well defined annular plaques with central scarring or pigmentation and raised keratotic border. Disseminated superficial actinic porokeratosis, linear porokeratosis, porokeratosispalmaris et plantaris ,punctateporokeratosis are different clinical variants. Keratotic border is microscopically characterized by a column of parakeratotic cells invaginating the epidermis known as cornoid lamella which is a characteristic finding. Porokeratosis localized to the genital region is very rare. These lesions are mostly asymptomatic but there can be occasional pruritus. It mostly occurs on the scrotum followed by penis however adjoining areas like thighs, buttocks, natal cleft can also be involved. There are very few reports in Indian literature of porokeratsis limited to the genital region.