A Double-Blind, Randomized, Placebo-Controlled, Phase II Clinical Study To Evaluate the Efficacy and Safety of Camostat Mesylate (DWJ1248) in Adult Patients with Mild to Moderate COVID-19.

Although several antiviral agents have become available for coronavirus disease 2019 (COVID-19) treatment, oral drugs are still limited. Camostat mesylate, an orally bioavailable serine protease inhibitor, has been used to treat chronic pancreatitis in South Korea, and it has an in vitro inhibitory potential against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This study was a double-blind, randomized, placebo-controlled, multicenter, phase 2 clinical trial in mild to moderate COVID-19 patients. We randomly assigned patients to receive either camostat mesylate (DWJ1248) or placebo orally for 14 days. The primary endpoint was time to clinical improvement of subject symptoms within 14 days, measured using a subjective 4-point Likert scale. Three hundred forty-two patients were randomized. The primary endpoint was nonsignificant, where the median times to clinical improvement were 7 and 8 days in the camostat mesylate group and the placebo group, respectively (hazard ratio [HR] = 1.09; 95% confidence interval [CI], 0.84 to 1.43; P = 0.50). A post hoc analysis showed that the difference was greatest at day 7, without reaching significance. In the high-risk group, the proportions of patients with clinical improvement up to 7 days were 45.8% (50/109) in the camostat group and 38.4% (40/104) in the placebo group (odds ratio [OR] = 1.33; 95% CI, 0.77 to 2.31; P = 0.31); the ordinal scale score at day 7 improved in 20.0% (18/90) of the camostat group and 13.3% (12/90) of the placebo group (OR = 1.68; 95% CI, 0.75 to 3.78; P = 0.21). Adverse events were similar in the two groups. Camostat mesylate was safe in the treatment of COVID-19. Although this study did not show clinical benefit in patients with mild to moderate COVID-19, further clinical studies for high-risk patients are needed. (This trial was registered with ClinicalTrials.gov under registration no. NCT04521296).

Hepatic STAMP2 alleviates polychlorinated biphenyl-induced steatosis and hepatic iron overload in NAFLD models.

Polychlorinated biphenyls (PCBs) have been associated with neurotoxicity, hepatoxicity, oncogenicity, and endocrine-disrupting effects. Although the recent studies have demonstrated that PCB exposure leads to nonalcoholic fatty liver disease (NAFLD), the underlying mechanism has remained unsolved. In this study, we examined the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, and PCB 126 in C57BL/6 mice. Male C57Bl/6 mice were fed a standard diet or a 60% high-fat diet and exposed to Aroclor 1260 (10 mg/kg or 20 mg/kg) or PCB 126 (1 mg/kg or 5 mg/kg) by intraperitoneal injection for a total of four injections (2, 3, 4, and 5 weeks) for 6 weeks. In mice, both Aroclor 1260 and PCB 126-induced liver damage, hepatic steatosis and inflammation. We also observed that PCB exposure-induced hepatic iron overload (HIO). We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable therapeutic target for NAFLD patients. Thus, we further examined whether hepatic STAMP2 is involved in PCB-induced NAFLD. We observed that hepatic STAMP2 was significantly decreased in PCB-induced NAFLD models in vivo and in vitro. Furthermore, overexpression of hepatic STAMP2 using an adenoviral delivery system resulted in improvement of PCB-induced steatosis and HIO in vivo and in vitro. Our findings indicate that enhancing hepatic STAMP2 expression represents a potential therapeutic avenue for the treatment of PCB exposure-induced NAFLD.

Infectivity of Coronavirus Disease 2019: A Prospective Cohort Study in the Korean Metropolitan Area.

BACKGROUND: Although several characteristics of coronavirus disease 2019 (COVID-19), an ongoing pandemic disease, have been identified, data on the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are limited. METHODS: This prospective cohort study was conducted to analyze the infectivity of SARS-CoV-2 based on data of all patients diagnosed with COVID-19 confirmed using real-time polymerase chain reaction test from January to April 2020 in Gyeonggi-do, the largest province in Korea. RESULTS: Of the 502 patients, 298 consisting of 106 clusters with 5,909 contacts were included. Of these, 277 (93.0%) were symptomatic, and the most common symptoms were cough, fever, sputum, sore throat, and headache. A total of 94 patients (31.5%) had pneumonia, while 8 (2.7%) died during the follow-up period. The secondary attack rate (SAR) in the study population was 3.5% (204/5,909). In exposure settings, the SAR was higher in religious gathering (13.5% [95% confidence interval, 10.7-16.8%]), workplaces (8.49% [95% CI, 6.08-11.74%]), and schools (6.38% [95% CI, 3.39-11.69%]) than in health care facilities (1.92% [95% CI, 1.45-2.55%]). Sore throat at any period, dyspnea at diagnosis or any period, lower cycle threshold value in the lower respiratory tract samples, leukocytosis, and higher bilirubin levels were associated with higher infectivity of COVID-19. The presence of symptoms was not related to the infectivity. CONCLUSION: In establishing the infection control strategies for COVID-19, the variables associated with high infectivity may be considered.

Clinical findings, viral load, and outcomes of COVID-19: Comparison of patients with negative and positive initial chest computed tomography.

Reports detailing the clinical characteristics, viral load, and outcomes of patients with normal initial chest CT findings are lacking. We sought to compare the differences in clinical findings, viral loads, and outcomes between patients with confirmed COVID-19 who initially tested negative on chest CT (CT negative) with patients who tested initially positive on chest CT (CT positive). The clinical data, viral loads, and outcomes of initial CT-positive and CT-negative patients examined between January 2020 and April 2020 were retrospectively compared. The efficacy of viral load (cyclic threshold value [Ct value]) in predicting pneumonia was evaluated using receiver operating characteristic (ROC) curve and area under the curve (AUC). In total, 128 patients underwent initial chest CT (mean age, 54.3 ± 19.0 years, 50% male). Of those, 36 were initially CT negative, and 92 were CT positive. The CT-positive patients were significantly older (P < .001) than the CT-negative patients. Only age was significantly associated with the initial presence of pneumonia (odds ratio, 1.060; confidence interval (CI), 1.020-1-102; P = .003). In addition, age (OR, 1.062; CI, 1.014-1.112; P = .011), fever at diagnosis (OR, 6.689; CI, 1.715-26.096; P = .006), and CRP level (OR, 1.393; CI, 1.150-1.687; P = .001) were significantly associated with the need for O2 therapy. Viral load was significantly higher in the CT-positive group than in the CT-negative group (P = .017). The cutoff Ct value for predicting the presence of pneumonia was 27.71. Outcomes including the mean hospital stay, intensive care unit admission, and O2 therapy were significantly worse in the CT-positive group than in the CT-negative group (all P < .05). In conclusion, initially CT-negative patients showed better outcomes than initially CT-positive patients. Age was significantly associated with the initial presence of pneumonia, and viral load may help in predicting the initial presence of pneumonia.

Clinical and Laboratory Factors Associated with Symptom Development in Asymptomatic COVID-19 Patients at the Time of Diagnosis.

In preparation for the surge of coronavirus disease 2019 (COVID-19), it is crucial to allocate medical resources efficiently for distinguishing people who remain asymptomatic until the end of the disease. Between January 27, 2020, and April 21, 2020, 517 COVID-19 cases from 13 healthcare facilities in Gyeonggi province, Korea, were identified out of which the epidemiologic and clinical information of 66 asymptomatic patients at the time of diagnosis were analyzed retrospectively. An exposure-diagnosis interval within 7 days and abnormal aspartate aminotransferase levels were identified as characteristic symptom development in asymptomatic COVID-19 patients. If asymptomatic patients without these characteristics at the time of diagnosis could be differentiated early, more medical resources could be secured for mild or moderate cases in this COVID-19 surge.

Rapidly Progressive Small Bowel Necrosis in a Previously Healthy Child without Proven Mechanical Obstruction.

Bowel ischemia is a life-threatening surgical emergency. We report a case of rapidly progressive bowel necrosis in a previously healthy child without proven mechanical small bowel obstruction. The definite diagnosis was established at the time of an exploratory operation. Of note, imaging studies and even a laparotomy did not reveal any evidence of acute appendicitis or mechanical obstruction such as intussusception or Meckel's diverticulum. During hospitalization, since we could not rule out surgical abdomen after inconclusive image findings, we closely followed the patient and repeated physical examinations carefully. Eventually surgical exploration was performed based on changes in clinical condition, which proved to be the right decision for the patient. We propose that in children with suspected strangulation of small bowel obstruction, especially when imaging findings do not provide a conclusive diagnosis, the timely exploratory surgical approach ought to be chosen based on carefully observed clinical findings and other evaluations.

Edge enhancement algorithm for low-dose X-ray fluoroscopic imaging.

BACKGROUND AND OBJECTIVE: Low-dose X-ray fluoroscopy has continually evolved to reduce radiation risk to patients during clinical diagnosis and surgery. However, the reduction in dose exposure causes quality degradation of the acquired images. In general, an X-ray device has a time-average pre-processor to remove the generated quantum noise. However, this pre-processor causes blurring and artifacts within the moving edge regions, and noise remains in the image. During high-pass filtering (HPF) to enhance edge detail, this noise in the image is amplified. METHODS: In this study, a 2D edge enhancement algorithm comprising region adaptive HPF with the transient improvement (TI) method, as well as artifacts and noise reduction (ANR), was developed for degraded X-ray fluoroscopic images. The proposed method was applied in a static scene pre-processed by a low-dose X-ray fluoroscopy device. First, the sharpness of the X-ray image was improved using region adaptive HPF with the TI method, which facilitates sharpening of edge details without overshoot problems. Then, an ANR filter that uses an edge directional kernel was developed to remove the artifacts and noise that can occur during sharpening, while preserving edge details. RESULTS: The quantitative and qualitative results obtained by applying the developed method to low-dose X-ray fluoroscopic images and visually and numerically comparing the final images with images improved using conventional edge enhancement techniques indicate that the proposed method outperforms existing edge enhancement methods in terms of objective criteria and subjective visual perception of the actual X-ray fluoroscopic image. CONCLUSIONS: The developed edge enhancement algorithm performed well when applied to actual low-dose X-ray fluoroscopic images, not only by improving the sharpness, but also by removing artifacts and noise, including overshoot.

Simple and accessible analytical methods for the determination of mercury in soil and coal samples.

Simple and accessible analytical methods compared to conventional methods such as US EPA Method 7471B and ASTM-D6414 for the determination of mercury (Hg) in soil and coal samples are proposed. The new methods are consisted of fewer steps without the Hg oxidizing step consequently eliminating a step necessary to reduce excess oxidant. In the proposed methods, a Hg extraction is an inexpensive and accessible step utilizing a disposable test tube and a heating block instead of an expensive autoclave vessel and a specially-designed microwave. Also, a common laboratory vacuum filtration was used for the extracts instead of centrifugation. As for the optimal conditions, first, best acids for extracting Hg from soil and coal samples was investigated using certified reference materials (CRMs). Among common laboratory acids (HCl, HNO3, H2SO4, and aqua regia), aqua regia was most effective for the soil CRM whereas HNO3 was for the coal CRM. Next, the optimal heating temperature and time for Hg extraction were evaluated. The most effective Hg extraction was obtained at 120°C for 30min for soil CRM and at 70°C for 90min for coal CRM. Further tests using selected CRMs showed that all the measured values were within the allowable certification range. Finally, actual soil and coal samples were analyzed using the new methods and the US EPA Method 7473. The relative standard deviation values of 1.71-6.55% for soil and 0.97-12.11% for coal samples were obtained proving that the proposed methods were not only simple and accessible but also accurate.

Clinical significance of variceal hemorrhage in recent years in patients with liver cirrhosis and esophageal varices.

BACKGROUND AND AIMS: Recent progress in the treatment of variceal bleeding might have reduced the impact of variceal bleeding on survival in patients with esophageal varices. We conducted a retrospective cohort study in an attempt to re-evaluate the clinical significance of variceal bleeding. METHODS: A cohort of 304 patients with liver cirrhosis and esophageal varices, who had no previous history of variceal bleeding and no prophylactic therapy, was studied. RESULTS: During a median follow-up period of 32 months, 55 patients (18%) bled from varices and 111 (37%) died. Variceal hemorrhages accounted for 15% of total deaths. The mortality of first variceal bleeding was 25% in the whole group, but was remarkably different depending on liver function at the time of bleeding (0% in grade Child A vs 55% in grade C; P < 0.05). Among the survivors of first bleeding, 30% experienced rebleeding. Form of varix, red color sign and heavy drinking were the independent risk factors for first variceal bleeding. Multivariate analysis revealed that variceal bleeding still had a significant (P < 0.001) impact on death in the whole cohort, when other independent prognostic factors such as age, ascites, encephalopathy, platelet count, serum albumin level and hepatocellular carcinoma were adjusted. Furthermore, in subgroup analyses, variceal bleeding was more strongly (P < 0.001) linked to death in patients with alcoholic cirrhosis than in those with non-alcoholic cirrhosis, and showed a significant association with survival only for the patients in Child grade B. CONCLUSIONS: Variceal bleeding has various prognostic impacts depending on the etiology of cirrhosis or on the degree of liver dysfunction, and this needs to be taken into account in the prophylaxis against first variceal bleeding.

[Idiopathic hypereosinophilic syndrome presenting as a single mass in the liver].

Hypereosinophilic syndrome is characterized by persistent blood eosinophilia of 1,500/mm(3) or more in the absence of known causes and multiorgan dysfunction by eosinophil-related tissue damage. In Korea, some cases of hypereosinophilic syndrome with hepatic involvement have been described with prolonged benign clinical courses. Most of them were diffuse or multifocal lesions in imaging studies, and any case presenting as a large single mass lesion has not been described. Herein we report a case of hypereosinophilic syndrome with hepatic involvement in a 48-year-old woman who presented with a giant single mass. By abdominal CT scan, a lobulated well-margined heterogenous mass lesion was detected in the left lateral segment of the liver. Liver biopsy revealed severe eosinophilic infiltration and centrilobular necrosis of hepatocytes. The lesion completely disappeared after steroid administration for eleven months.

[An analysis of extravariceal collaterals of gastric varices using magnetic resonance angiography in portal hypertensive patients].

BACKGROUND/AIMS: This study was aimed to analyze the relationship between gastric varices and its collaterals using magnetic resonance angiography (MRA) and to assess the usefulness of MRA in studies of portosystemic circulation. METHODS: Eighty-one patients who had portal hypertension with gastric varices took MRA before the therapy for gastric varices. RESULTS: The types of collaterals observed by MRA were left gastric vein in 67 patients (83%), short gastric vein in 28 (35%), gastrorenal shunt in 25 (31%), and splenorenal shunt in 14 (17%). In most of patients with advanced gastric varices, the size of left gastric vein was larger than others. In most cases of large gastric varices, the short gastric vein ranged between 5 to 10 mm. Gastrorenal shunt was also correlated with the size of gastric varices. The types of more prominent esophageal varices showed a right type (left gastric vein predominance), but the types of more prominent gastric varices or only the gastric varices showed a left type (posterior or short gastric vein predominance) (p<0.05). CONCLUSIONS: Gadolinium enhanced 3D-MRA can contribute to the study of the hemodynamic relationships between gastric vein and the collateral circulations by presenting more clear images for patients with portal hypertension.

[Two cases of autoimmnune hepatitis associated with systemic lupus erythematosus].

Autoimmune hepatitis (AIH) is a chronic necroinflammatory liver disease of unknown cause associated with circulating autoantibodies and high serum globulin level. Systemic lupus erythematosus (SLE) is a disease of unknown etiology in which tissues and cells are damaged by pathogenic autoantibodies and immune complex, affecting multiple organs including the liver, kidney, and CNS. The difference between the hepatic involvement of SLE and autoimmune hepatitis has not been clearly defined in the past due to similarities in clinical and biochemical features. A scoring system for the diagnosis of AIH has been established, and AIH and SLE-associated hepatitis have been defined as two different entities, although both have the same autoimmune features such as polyarthralgia, hypergammaglobulinemia and circulating autoantibodies. AIH has been considered to occur infrequently in SLE. We report two cases of AIH which simultaneously satisfied the criteria of SLE.

[A case of auto-immune hepatitis associated with primary Sjogren's syndrome].

Auto-immune hepatitis is a chronic necroinflammatory liver disorder that is characterized by hypergammaglobulinemia, auto-antibodies in serum, and, on histological examination, the presence of periportal hepatitis. Although it can be associated with a number of other auto-immune diseases, Sjogren's syndrome is rarely associated with auto-immune hepatitis. We herein report an unusual case of auto-immune hepatitis associated with primary Sjogren's syndrome. A 39-year-old woman was admitted to our hospital due to jaundice. Laboratory data showed negative viral hepatitis marker, increased serum IgG level, positive anti- nuclear antibody, and an increased rheumatoid factor titer. The patient had no history of taking medications and alcohol. Based on characteristic clinical features, liver biopsy findings, positive Schirmer's test, and salivary scintigraph, she was diagnosed as having auto-immune hepatitis and Sjogren's syndrome. The patient achieved complete remission with steroid monotherapy.

Electron microscopic evaluation of adhesion of Helicobacter pylori to the gastric epithelial cells in chronic gastritis.

BACKGROUND: The adhesion of H. pylori to the gastric epithelial cells may be an essential step for the pathophysiology of various H. pylori-induced gastrointestinal diseases. The purpose of this study was to investigate the ultrastructural relation of H. pylori and gastric epithelial cells in their adhesion. METHODS: Endoscopic biopsy of gastric antrum and body was performed from 15 patients (9 men, 6 women) with chronic gastritis and H. pylori infection. The specimens were processed for electron microscopy and observed with a transmission electron microscope (Hitachi H-600). RESULTS: On the basis of morphological appearances, the adhesions of H. pylori to the gastric epithelial cells were categorized into three types; filamentous connection, adhesion pedestals and membrane fusion. Coccoid and undetermined forms adhered mainly by the filamentous connection, whereas the bacillary forms adhered primarily by the adhesion pedestals and membrane fusion. CONCLUSION: Various types of adhesion were associated with H. pylori and gastric epithelium. Further studies are needed to evaluate the influence of different types of adhesion to the pathophysiology of H. pylori.