Differentiating malignant and benign eyelid lesions using deep learning.

Artificial intelligence as a screening tool for eyelid lesions will be helpful for early diagnosis of eyelid malignancies and proper decision-making. This study aimed to evaluate the performance of a deep learning model in differentiating eyelid lesions using clinical eyelid photographs in comparison with human ophthalmologists. We included 4954 photographs from 928 patients in this retrospective cross-sectional study. Images were classified into three categories: malignant lesion, benign lesion, and no lesion. Two pre-trained convolutional neural network (CNN) models, DenseNet-161 and EfficientNetV2-M architectures, were fine-tuned to classify images into three or two (malignant versus benign) categories. For a ternary classification, the mean diagnostic accuracies of the CNNs were 82.1% and 83.0% using DenseNet-161 and EfficientNetV2-M, respectively, which were inferior to those of the nine clinicians (87.0-89.5%). For the binary classification, the mean accuracies were 87.5% and 92.5% using DenseNet-161 and EfficientNetV2-M models, which was similar to that of the clinicians (85.8-90.0%). The mean AUC of the two CNN models was 0.908 and 0.950, respectively. Gradient-weighted class activation map successfully highlighted the eyelid tumors on clinical photographs. Deep learning models showed a promising performance in discriminating malignant versus benign eyelid lesions on clinical photographs, reaching the level of human observers.

Tangent functional canonical correlation analysis for densities and shapes, with applications to multimodal imaging data.

It is quite common for functional data arising from imaging data to assume values in infinite-dimensional manifolds. Uncovering associations between two or more such nonlinear functional data extracted from the same object across medical imaging modalities can assist development of personalized treatment strategies. We propose a method for canonical correlation analysis between paired probability densities or shapes of closed planar curves, routinely used in biomedical studies, which combines a convenient linearization and dimension reduction of the data using tangent space coordinates. Leveraging the fact that the corresponding manifolds are submanifolds of unit Hilbert spheres, we describe how finite-dimensional representations of the functional data objects can be easily computed, which then facilitates use of standard multivariate canonical correlation analysis methods. We further construct and visualize canonical variate directions directly on the space of densities or shapes. Utility of the method is demonstrated through numerical simulations and performance on a magnetic resonance imaging dataset of glioblastoma multiforme brain tumors.

Elastic Statistical Shape Analysis of Biological Structures with Case Studies: A Tutorial.

We describe a recent framework for statistical shape analysis of curves and show its applicability to various biological datasets. The presented methods are based on a functional representation of shape called the square-root velocity function and a closely related elastic metric. The main benefit of this approach is its invariance to reparameterization (in addition to the standard shape-preserving transformations of translation, rotation and scale), and ability to compute optimal registrations (point correspondences) across objects. Building upon the defined distance between shapes, we additionally describe tools for computing sample statistics including the mean and covariance. Based on the covariance structure, one can also explore variability in shape samples via principal component analysis. Finally, the estimated mean and covariance can be used to define Wrapped Gaussian models on the shape space, which are easy to sample from. We present multiple case studies on various biological datasets including (1) leaf outlines, (2) internal carotid arteries, (3) Diffusion Tensor Magnetic Resonance Imaging fiber tracts, (4) Glioblastoma Multiforme tumors, and (5) vertebrae in mice. We additionally provide a MATLAB package that can be used to produce the results given in this manuscript.

The Spectrum of Hepatic Involvement in Patients With Telomere Disease.

Loss-of-function mutations in genes that encode for components of the telomere repair complex cause accelerated telomere shortening. Hepatic involvement has been recognized as a cause of morbidity in telomere diseases, but very few studies have characterized the nature and extent of liver involvement in affected patients. We report the prevalence and characteristics of liver involvement in a large cohort of patients with telomere disease evaluated serially at the National Institutes of Health. One hundred twenty-one patients with known or suspected telomere disease were screened; 40 patients with liver involvement were included in the current study. Median follow-up was 2.4 years. Data were collected regarding their demographic information, laboratory analysis, imaging, and histopathology. Forty patients (40% of the cohort) with a median age of 42 years were found to have liver involvement. Liver enzyme elevation was cholestatic in pattern; 8 (21%) had drug-related enzyme elevations. The most common imaging finding was increased hepatic echogenicity on ultrasound in 39% (9) of patients, followed by hepatomegaly in 26% (6). Biopsies were infrequent because of risk associated with thrombocytopenia, but in 6 patients, there were varying findings: nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, and cirrhosis with hepatic steatosis. Almost half the cohort had pulmonary diffusion abnormalities, and 25% died during the follow-up period. Conclusion: In patients with telomere disease, hepatic involvement is common and can present in diverse ways, including elevated liver enzymes as well as histopathologic and imaging abnormalities. Liver disease has important implications for morbidity and mortality in patients with telomere disease.

Development of Hepatic Steatosis After Chemotherapy for Non-Hodgkin Lymphoma.

Nonalcoholic fatty liver disease is the most common liver disorder in the developed world. Although typically reflecting caloric overload, it can also be secondary to drug toxicity. We aimed to describe the incidence and risk factors for de novo steatosis during chemotherapy for non-Hodgkin lymphoma (NHL). In this retrospective case-control study, adult patients with NHL were treated with rituximab, cyclophosphamide, doxorubicin, prednisone, and vincristine (R-CHOP) or R-CHOP + etoposide (EPOCH-R). Patients with liver disease or steatosis were excluded. Abdominal computed tomography was performed pretreatment and at 3- to 6-month intervals and reviewed for steatosis. Patients with de novo steatosis were matched 1:1 to controls by age, sex, and ethnicity. Of 251 treated patients (median follow-up 53 months), 25 (10%) developed de novo steatosis, with the vast majority (23 of 25; 92%) developing it after chemotherapy. Of those, 14 (61%) developed steatosis within the first 18 months posttreatment and 20 (87%) within 36 months. Cases had higher baseline body mass index (BMI; mean ± SD, 29.0 ± 6.5 versus 26.0 ± 5.2 kg/m2; P = 0.014) and hyperlipidemia (12% versus 2%; P = 0.035). Although their weights did not change during chemotherapy, BMI in cases increased by 2.4 ± 2 kg/m2 (mean ± SD) from end of treatment to steatosis compared to 0.68 ± 1.4 in controls (P = 0.003). Etoposide-containing regimens were associated with a shorter time to steatosis (median 34 weeks versus 154 weeks; P < 0.001) despite similar baseline risk factors. Conclusion: The recovery period from NHL chemotherapy appears to be a "hot spot" for development of fatty liver, driven by early posttreatment weight gain, especially in subjects with baseline risk factors.

Use of direct-acting antivirals for hepatitis C viral infection and association with intrahepatic cholangiocarcinoma: Is there a linkage?

Hepatitis C viral infection is recognized worldwide as a leading cause of cirrhosis and hepatocellular carcinoma. The goal of hepatitis C viral antiviral therapy is the permanent eradication of hepatitis C viral RNA, commonly referred to as a sustained virologic response - defined as "undetectable" RNA at 12 weeks following the completion of therapy. Hepatitis C viral treatment has dramatically advanced with the FDA approval of several new agents known as direct-acting antivirals. These drugs target specific nonstructural proteins of the virus, which disrupt viral replication, and therefore halt infection. However, recently, there has been a concern for increased risk of recurrence of treated hepatocellular carcinoma or denovo occurrence of hepatocellular carcinoma after treatment with direct-acting antivirals. We are now reporting three cases of intrahepatic cholangiocarcinoma that developed after sustained virologic response following hepatitis C viral treatment with direct-acting antivirals.

Biliary Obstruction due to a Pancreatic Plasmacytoma.

Obstructive jaundice, weight loss, and anorexia often raise a concern for pancreatic malignancy. Although pancreatic adenocarcinoma is the most common form of pancreatic cancer, not all pancreatic malignancies are exocrine in origin. With advancement in endoscopic ultrasound with fine needle aspiration, it has become easier to make correct diagnosis. Plasmacytoma of pancreas is a solitary tumor of plasma cells and it can also lead to the same clinical presentations. Immunohistochemistry is required to make the diagnosis of plasmacytoma. However, when there are other systemic manifestations, such as hypercalcemia, renal injury, and anemia, a diagnosis of multiple myeloma should be suspected and confirmed by cytology or biopsy. It is very important to differentiate plasmacytoma from multiple myeloma as the management for each is different. Herein, we describe a case of multiple myeloma presenting as a pancreatic plasmacytoma causing obstructive jaundice.

A case report of symptomatic presacral myelolipoma.

RATIONALE: Extra-adrenal myelolipoma in the presacral area often raises a concern for liposarcoma because they have similar radiologic features. PATIENT CONCERNS: A 70-year-old woman with multiple abdominal surgeries in the past presented with persistent lower abdominal pain and anemia. A presacral mass, found on a pelvic magnetic resonance image (MRI), was suspicious of liposarcoma, as it is the most common fat containing mass in the presacral area. It is often difficult to make a diagnosis of myelolipoma just based on the radiological studies, which necessitates a histopathologic examination of the resected mass for a definitive diagnosis. DIAGNOSES: Myelolipoma is an encapsulated, benign tumor containing mature adipocytes and hematologic cells. Most of the patients with myelolipoma remain asymptomatic but continued growth of tumor without local invasion can lead to compression of nearby structures, causing persistent pain. INTERVENTIONS: Asymptomatic patients do not require intervention but surgical resection is indicated for persistent pain or hemorrhage inside the tumor. Our patient had 2 indications for surgery - persistent pain as well as a provisional diagnosis of liposarcoma. After the surgical resection, pelvic pain was resolved, and a diagnosis of myelolipoma was made based on histopathologic examination. OUTCOMES: Patient was reassured that it was myelolipoma, a benign tumor, not requiring subsequent surveillance for recurrence. LESSONS: Despite advancement in imaging techniques, and knowledge of the radiological features of myelolipoma, it still remains as a challenge for clinicians to make the distinction between liposarcoma and myelolipoma only based on diagnostic radiology. Although myelolipoma is a benign tumor, if patient suffers from persistent pain due to local mass effect, surgical resection is required.

Effects of PRELI in Oxidative-Stressed HepG2 Cells.

Protein of relevant evolutionary and lymphoid interest (PRELI) is known for preventing apoptosis by mediating intramitochondrial transport of phosphatidic acid. However, the role of PRELI remains unclear. This study has demonstrated functions of PRELI through PRELI-knockdown in hepatocellular carcinoma (HepG2) cells exposed to oxidative stress by hydrogen peroxide. Results show that PRELI has three functions in HepG2 cells with regard to oxidative stress. First, PRELI affects expressional regulation of SOD-1 and caspase-3 genes in HepG2 cells. PRELI knockdown HepG2 cells have shown up-regulation of caspase-3 and down-regulation of SOD-1. Second, PRELI suppresses mitochondrial apoptosis in HepG2 cells. Fluorescence intensity related to mitochondrial apoptosis in PRELI-knockdown HepG2 cells increased more than two-fold compared to normal HepG2 cells. Third, PRELI suppresses senescence of HepG2 cells with oxidative stress. PRELI knockdown HepG2 cells showed higher levels of senescence than normal HepG2 cells. These results suggest that PRELI is a crucial protein in the suppression of apoptosis in HepG2 cells in response to oxidative stress.

Predictive clinical parameters for the therapeutic efficacy of sitagliptin in korean type 2 diabetes mellitus.

BACKGROUND: Sitagliptin is a highly selective dipeptidyl peptide-4 (DPP-4) inhibitor that increases blood levels of active glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrophic polypeptide (GIP), resulting in increased insulin secretion. While studies conducted in other countries have indicated the efficacy and safety of using sitagliptin to treat type 2 diabetes mellitus (T2DM), its predictors of effects to sitagliptin are not well understood. Therefore, we evaluated the predictive clinical parameters for the therapeutic benefits of sitagliptin when added to an ongoing metformin or sulfonylurea therapy in Korean T2DM subjects. METHODS: We obtained data from 251 Korean T2DM subjects who had recently started taking sitagliptin as add-on therapy. Exclusion criteria included any insulin use. Changes in HbA1c (ΔHbA1c) and fasting plasma glucose (ΔFPG) were assessed by comparing baseline levels prior to sitagliptin administration to levels 12 and 24 weeks after treatment. Responders were defined as subjects who experienced decrease from baseline of >10% in ΔHbA1c or >20% in ΔFPG levels at 24 weeks. RESULTS: We classified 81% of the subjects (204 out of 251) as responders. The responder group had a lower mean body mass index (23.70±2.40 vs. 26.00±2.26, P≤0.01) and were younger (58.83±11.57 years vs. 62.87±12.09 years, P=0.03) than the non-responder group. CONCLUSION: In Korean T2DM subjects, sitagliptin responders had lower body mass index and were younger compared to non-responders.

Effect of pioglitazone on serum concentrations of osteoprotegerin in patients with type 2 diabetes mellitus.

OBJECTIVE: Osteoprotegerin (OPG) acts as an important regulatory molecule in atherosclerosis. Recent studies report that thiazolidinediones could affect OPG expression. We investigated the relationship between OPG and inflammatory cytokines and the effects of pioglitazone (a PPARγ (PPARG) agonist) versus metformin on serum OPG levels in type 2 diabetic patients. DESIGN AND METHODS: Sixty-seven type 2 diabetic patients were included in this study. They were assigned to pioglitazone (15 mg/day, n=34) or metformin (1000 mg/day, n=33) during 24 weeks. Various anthropometric and metabolic parameters, OPG, interleukin 6 (IL6), C-reactive protein (CRP), adiponectin, and homeostasis model assessment of insulin resistance (HOMA-IR), were measured at baseline and at 6 months of treatment. RESULTS: Serum OPG levels correlated significantly with fasting plasma glucose (FPG), HbAlc, HOMA-IR, IL6, and CRP, and inversely correlated with adiponectin after adjusting for age (P<0.05). Multiple regression analysis showed that FPG, HbAlc, and adioponectin were independently correlated with OPG level. After 6 months of treatment, the reduction in FPG and HbAlc levels was similar between the two groups. Pioglitazone treatment significantly increased body mass index (P<0.05) and waist circumference (P<0.05) and decreased triglycerides (P<0.05) and HOMA-IR (P<0.01). The adiponectin concentration was increased (P<0.05), and OPG and CRP levels were decreased in the pioglitazone group (P<0.05), but were unchanged in the metformin group. The changes in serum OPG in the pioglitazone group showed significant correlation with changes in FPG, HbAlc, and adiponectin. CONCLUSIONS: In type 2 diabetic patients, pioglitazone decreases OPG levels, and this decrease in OPG levels might be associated with the increase in adiponectin.

Riedel's thyroiditis in a patient with recurrent subacute thyroiditis: a case report and review of the literature.

Riedel's thyroiditis is a rare form of chronic thyroiditis, characterised by a fibroinflammatory process that partially destroys the thyroid and often involves surrounding tissues. The relationship of Riedel's thyroiditis to other forms of thyroiditis is not clear. A case of Riedel's thyroiditis in a 51-year-old woman presenting with symptoms of subacute thyroiditis, is reported. She was diagnosed with subacute thyroiditis based on clinical manifestation and laboratory results. She was treated with glucocorticoids for six weeks, and then followed-up for 12 months. Three years later, she visited with tenderness and enlargement of thyroid mass, and laboratory and radiology findings suggested that she had a malignant thyroid tumor as well as subacute thyroiditis. After thyroidectomy, histopathologic findings showed that she had Riedel's thyroiditis in the presence of subacute thyroiditis. Until now, few cases of Riedel's thyroiditis in patients with a history of subacute thyroiditis have been reported in the literature. Although the etiology of Riedel's thyroiditis is unknown, it may develop in the course of subacute thyroiditis.

Gastric syphilis mimicking adenocarcinoma: a case report.

Syphilis is an unexpected diagnosis in the stomach, and the reduced incidence of syphilis has made its clinical presentation less widely appreciated. We report a 43-yr-old man suffering from epigastric tenderness with an initial diagnosis of gastric carcinoma; gastric syphilis was confirmed by demonstrating spirochetes in a gastric biopsy specimen by silver impregnation. Excessive lymphoplasmacytic infiltration with diffuse thickening of gastric rugae should raise suspicion of gastric syphilis, which should be considered in the differential diagnosis of diffuse erosive gastritis and infiltrative lesions of the stomach.