Treatment of direct oral anticoagulants in patients with liver cirrhosis and portal vein thrombosis

Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.     

Epidemiology of Macrosomia in Korea: Growth and Development

BackgroundMacrosomia, as an infant with birth weight over 4 kg, can have several perinatal, and neonatal complications. This study aimed to estimate the incidence of macrosomia in Korea and to identify the growth and developmental outcomes and other neonatal complications.MethodsIn total, 397,203 infants who were born in 2013 with birth weight ≥ 2.5 kg and who underwent infant health check-up between their 1^st and 7^th visit were included from the National Health Insurance Service database. The information was obtained by the International Classification of Diseases-10 codes or self-reported questionnaires in the National Health Screening Program.ResultsThe distribution of infants by birth weight was as follows: 384,181 (97%) infants in the 2.5–3.99 kg (reference) group, 12,016 (3%) infants in the 4.0–4.49 kg group, 772 (0.2%) infants in the 4.5–4.99 kg group, and 78 (0.02%) infants in the ≥ 5 kg group. Macrosomia showed significantly higher incidence of sepsis, male sex, and mothers with GDM and birth injury. There was a significant difference in weight, height, and head circumference according to age, birth weight group, and combination of age and birth weight, respectively (P < 0.001). The number of infants with the weight above the 90^th percentile in macrosomia at each health check-up showed higher incidence than in reference group. The mean body mass index significantly differed among the groups, as 50.6 in infants with 2.5–3.99 kg of birth weight, 63.5 with 4.0–4.49 kg, 71.0 with 4.5–4.99 kg, and 73.1 with ≥ 5 kg. There was a significant difference in the incidence of poor developmental results between infants with macrosomia and the reference group at 24, 36 and 48 month of age.ConclusionMacrosomia was significantly associated with the risk of sepsis, birth injury, obesity and developmental problem especially in a boy born from mothers with gestational diabetes mellitus. Careful monitoring and proper strategies for monitoring growth and development are needed.     

E-cigarette-associated Severe Pneumonia in Korea Using Data Linkage between the Korea National Health and Nutrition Examination Survey (KNHANES, 2013–2019) and the National Health Insurance Service (NHIS) Claims Database

BackgroundThis study aimed to investigate the association between e-cigarette (EC) use and development of acute severe pneumonia in the Korean population using a national database.MethodsWe conducted a retrospective analysis using linkage of data between the Korean National Health and Nutrition Examination Survey (KNHANES) and the National Health Insurance Service (NHIS) administrative claims database. The primary endpoint of this study was development of severe pneumonia requiring hospital admission according to EC use during the study period. The secondary endpoints were in-hospital mortality, intensive care unit (ICU) admission, ventilator care, and days of hospital stay.ResultsThe final analysis included 28,950 individuals, of which 578 (2.0%) were EC users. EC users were younger and more often male than non-EC users. The EC users showed higher level of education and household income and had fewer comorbidities. Severe pneumonia was noted in 37 of 28,372 non-EC users (0.13%), but there were no occurrences of severe pneumonia in EC users. The incidence of pneumonia occurrence was not different between the two groups (P = 1.000).ConclusionsSince e-cigarette or vaping use-associated lung injury (EVALI) is most likely included in acute severe pneumonia occurring within 3 months of EC use, it is considered that there might be no EVALI patients in Korea during the investigation period. A large-scale, prospective study is necessary to evaluate the association between EC use and acute lung injury.     

Alveolar type II cell abnormalities and peroxide formation in lungs of rats given IL-1 intratracheally

Acute lung injury (ALI) is characterized by increased lung levels of proinflammatory cytokines, inflammation, oxidative stress, edema, and impaired gas exchange. Notably, ALI patients also exhibit pulmonary surfactant abnormalities, including increased levels of phospholipids in their lung lavages. In the present study, to assess early alterations of the lung surfactant system in ALI, we induced inflammation and acute lung injury in rats by administering interleukin-1 (IL-1) intratracheally. Five h after IL-1 instillation, we examined lung tissue ultrastructure by electron microscopy using both routine staining methods and cerium chloride staining to localize hydrogen peroxide (H₂O₂) histologically. We also measured lung lavage phospholipid levels, lung tissue -glutamyl transpeptidase (GGT) activities (a marker of oxidative stress), and arterial blood oxygen tensions. We observed that lungs of rats given IL-1 intratracheally had increased neutrophil accumulation, increased H₂O₂ production, and increased alveolar type II (ATII) pneumocyte ultrastructural abnormalities compared to rats given saline intratracheally. Intratracheal instillation of IL-1 also increased phospholipid levels in the bronchoalveolar lavage (BAL), possibly as a consequence of the abnormal discharge of lamellar bodies into the alveolar lumen. In addition, IL-1-insufflated rats had increased lung GGT levels and impaired blood oxygenation compared to saline-insufflated rats. Treatment with mepacrine decreased lung neutrophil accumulation, ultrastructural lung abnormalities, lung lavage phospholipid levels, lung tissue GGT levels, and blood oxygenation impairment in rats given IL-1 intratracheally, suggesting a possible relationship between these events. Our results indicate that IL-1-induced acute lung injury in rats is marked by neutrophil-dependent oxidative stress, ATII cell defects, abnormal discharge of lamellar body phospholipids, and impaired blood oxygenation.     

Serologic heterogeneity of HLA-A24 correlates with allelic types in the Korean population

HLA-A24 is the second most frequently expressed HLA-A type in Koreans (GF 22.8%). Four different serologic reaction patterns were observed in Korean A24 positive samples using a commercial serologic typing kit. To clarify the nature of serologic heterogeneity, thirteen A24 positive DNA samples representing the four different serologic reaction patterns were subjected to DNA sequencing analysis of the amplified HLA-A genes from each sample. Four A*24 alleles (A*2402101, A*2403, A*2408, and A*2421) were associated with the four unique serologic reaction patterns. During this study, a novel allele, A*2421, was characterized. The new sequence is similar to A*2402101, differing at codon 127 (AAA-->AAC; K-->N). By comparing putative amino acid sequences and serologic reaction patterns of A*24 allelic products identified in this study, several crucial sites for A24- and A9-specific antibody binding were predicted: 127K for A24 antibody binding, and 62E-65G and 166D-167G for A9 antibody binding. This information will be helpful for accurately assigning HLA-A24 types by serology and for predicting serologic types of new alleles.     

Relationship between normal heart size and body indices in Korean

We provided a curve-fit equation to predict the normal heart weight (g) in Koreans by examining 422 autopsies (215 males and 207 females, from newborn to age 77 yr) who were relatively in good general condition. Heart weight was well correlated with body surface area (m2), body weight (kg), and body height (cm) but poorly with age in both sex. Heart weight progressively increased from birth to the earlier 3rd and 4th decades in male and female, respectively, and then gradually decreased; mean heart weight of all age group was greater in male than in female and significantly different from birth to 4th decade. In both sex, heart weight exponentially increased in accordance with the increase of body height, body weight, and body surface (in male, heart weight=0.00312 x body height(2.239), r2=0.750, p<0.0001; in female, heart weight=0.00443 x body height(2170), r2=0.781, p<0.0001; in male, heart weight=9.22 x body weight(0.853), r2=0.770, p<0.0001; in female, heart weight=9.00 x body weight0.855, r2=0.820, p<0.0001; in male, heart weight=155.18 x body surface area1.290, r=0.808, p<0.0001; in female, heart weight=124.13 x body surface area1.242, r=0.834, p<0.0001). These results indicate that heart weight is better correlated with body surface area than with body weight; however, body weight should be a better determinant of a predicted heart weight, since body surface area is entirely dependent on body height and body weight.     

Two cases of chronic pancreatitis with pseudocyst complicated by obstructive jaundice

We recently treated two cases of chronic pancreatitis with obstructive jaundice due to compression of the common bile duct by pancreatic pseudocyst. The two cases were males admitted with the complaint of icteric skin color. The first, a 46-year-old male, admitted with the complaint of icteric skin color. He was treated by operative cystojejunostomy after percutaneous drainage of the pseudocyst and percutaneous transhepatic biliary drainage. The other case was a 58 year-old male who admitted with the complaint of icteric skin color. He had an infected pseudocyst in the pancreas and was endoscopically treated. Both of them were discharged with favorable clinical course and normal laboratory findings after the treatment. The former patient remained well 11 months after treatment, but the latter patient died from necrotizing pancreatitis and septic shock 6 months after treatment. Most cases of obstructive jaundice associated with pseudocysts appear to be due to fibrotic stricture of the intrapancreatic portion of the common bile duct rather than due to compression of the bile duct by the pseudocyst. In a patient with secondary pancreatic infection or obstructive jaundice following pancreatic disease, differentiating between these two conditions is an important aspect of accurate diagnosis and therapy. Herein we report two unusual cases of chronic pancreatitis with pseudocyst complicated by obstructive jaundice.     

Proteomic analysis of psoriatic skin tissue for identification of differentially expressed proteins: up-regulation of GSTP1, SFN and PRDX2 in psoriatic skin

Psoriasis is a chronic inflammatory skin disease, characterized by a combination of abnormal proliferation of keratinocytes, immunology and vascular proliferation. Proteomic analyses have revealed some clues regarding the pathogenesis of psoriasis. In the present study, we conducted an investigation of different proteomes of psoriatic lesional skin, and compared them with those of normal and non-lesional psoriatic skin. We performed 2-D gel electrophoresis, liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis and database searches. Expression of proteins were evaluated by immunoblot and immunohistochemistry analyses. Our data showed differential expression of 74 and 145 protein spots in non-lesional and lesional psoriatic skin, respectively. Eleven of 36 proteins, which were identified by LC-MS/MS, were categorized as apoptosis-regulating proteins. Other protein spots were categorized as proteins with involvement in the negative regulation of apoptosis, defense response-related proteins and inflammatory response. Of particular interest, increased expression of glutathione S transferase 1 (GSTP1) and peroxiredoxin 2 (PRDX2), which are involved in the Redox balance system, and SFN, which is involved in the cellular proliferation system, was observed in psoriatic lesional skin. Localization of GSTP1 and SFN was observed above the middle layer of the epidermis in psoriatic skin lesions. Expression of PRDX2 was clearly observed below the middle layer of the epidermis in chronic type psoriatic skin lesions. Taken together, 36 identified proteins were associated with biological regulation, including regulation of cell death, defense response, inflammatory response and reactive oxygen species (ROS) regulation. PRDX2 and GSTP1 may play roles in compensating mechanisms for reduction of ROS stress, and SFN may play roles in prevention of cancer development in proliferating cells through G2/M cell cycle arrest upon accidental DNA damage within psoriatic skin lesions.     

Association of harm avoidance with dopamine D2/3 receptor availability in striatal subdivisions: a high resolution PET study

We examined the relationship between the personality trait of harm avoidance (HA) and the dopamine D_2/3 receptor availability in striatal subdivisions using high resolution positron emission tomography (PET) with [¹¹C]raclopride. Twenty-one healthy subjects completed 3 T magnetic resonance imaging and high resolution PET scans with [¹¹C]raclopride in order to measure D_2/3 receptor availability in subregions of the striatum. The D_2/3 receptor availability was obtained on the basis of the Logan graphical method. The Temperament and Character Inventory was used to measure the biogenetic temperament of HA. The analysis revealed that the HA score had significant negative correlations with D_2/3 receptor availability in the pre-commissural dorsal caudate and post-commissural putamen, suggesting that HA is associated with D_2/3 receptor availability in the associative and sensorimotor subdivisions of the striatum, which are mainly involved in cognition and locomotion. Further research is required to determine if pathological states have similar dopaminergic mechanisms in specific striatal subdivisions.     

Immunotherapy of malignant melanoma with tumor lysate-pulsed autologous monocyte-derived dendritic cells

Purpose

Dendritic cell (DC) vaccination for melanoma was introduced because melanoma carries distinct tumor-associated antigens. The purpose of this study was to investigate the efficacy and safety of DC vaccination for melanoma in Korea.

Materials and Methods

Five patients with stage IV and one with stage II were enrolled. Autologous monocyte-derived DCs (MoDCs) were cultured and pulsed with tumor-lysate, keyhole limpet hemocyanin, and cytokine cocktail for mature antigen-loaded DC. DC vaccination was repeated four times at 2-week intervals and 2-4×10⁷ DC were injected each time.

Results

Reduced tumor volume was observed by PET-CT in three patients after DC vaccination. Delayed type hypersensitivity responses against tumor antigen were induced in five patients. Tumor antigen-specific IFN-γ-producing peripheral blood mononuclear cells were detected with enzyme-linked immunosorbent spot in two patients. However, the overall clinical outcome showed disease progression in all patients.

Conclusion

In this study, DC vaccination using tumor antigen-loaded, mature MoDCs led to tumor regression in individual melanoma patients. Further standardization of DC vaccination protocol is required to determine which parameters lead to better anti-tumor responses and clinical outcomes.