Adverse events and preventive measures related to COVID-19 vaccines

The coronavirus disease 2019 (COVID-19) vaccines are categorized according to the manufacturing technique, including mRNA vaccines and adenovirus vector vaccines. According to previous studies, the reported efficacy of the COVID-19 vaccine is excellent regardless of the type of vaccine, and the majority of studies have shown similar results for safety. Most of the adverse reactions after vaccination were mild or moderate grade, and severe reactions were reported in a very small proportion. However, the adverse reactions that might occur after nationwide vaccinations can contribute to crowding of emergency departments, and this can further lead to significant obstacles to providing necessary treatment for life-threatening conditions. Therefore, as emergency physicians, we would like to present some concerns and suggestions to prevent these predictable problems.

Adverse events and preventive measures related to COVID-19 vaccines

The coronavirus disease 2019 (COVID-19) vaccines are categorized according to the manufacturing technique, including mRNA vaccines and adenovirus vector vaccines. According to previous studies, the reported efficacy of the COVID-19 vaccine is excellent regardless of the type of vaccine, and the majority of studies have shown similar results for safety. Most of the adverse reactions after vaccination were mild or moderate grade, and severe reactions were reported in a very small proportion. However, the adverse reactions that might occur after nationwide vaccinations can contribute to crowding of emergency departments, and this can further lead to significant obstacles to providing necessary treatment for life-threatening conditions. Therefore, as emergency physicians, we would like to present some concerns and suggestions to prevent these predictable problems.

MeBib Suppressed Methamphetamine Self-Administration Response via Inhibition of BDNF/ERK/CREB Signal Pathway in the Hippocampus

Methamphetamine (MA) is one of the most commonly abused drugs in the world by illegal drug users. Addiction to MA is a serious public health problem and effective therapies do not exist to date. It has also been reported that behavior induced by psychostimulants such as MA is related to histone deacetylase (HDAC). MeBib is an HDAC6 inhibitor derived from a benzimidazole scaffold. Many benzimidazole-containing compounds exhibit a wide range of pharmacological activity. In this study, we investigated whether HDAC6 inhibitor MeBib modulates the behavioral response in MA self-administered rats. Our results demonstrated that the number of active lever presses in MA self-administered rats was reduced by pretreatment with MeBib. In the hippocampus of rats, we also found MA administration promotes GluN2B, an NMDA receptor subunit, expression, which results in sequential activation of ERK/CREB/BDNF pathway, however, MeBib abrogated it. Collectively, we suggest that MeBib prevents the MA seeking response induced by MA administration and therefore, represents a potent candidate as an MA addiction inhibitor.

Epicatechin Prevents Methamphetamine-Induced Neuronal Cell Death via Inhibition of ER Stress

Methamphetamine (METH) acts strongly on the nervous system and damages neurons and is known to cause neurodegenerative diseases such as Alzheimer's and Parkinson's. Flavonoids, polyphenolic compounds present in green tea, red wine and several fruits exhibit antioxidant properties that protect neurons from oxidative damage and promote neuronal survival. Especially, epicatechin (EC) is a powerful flavonoid with antibacterial, antiviral, antitumor and antimutagenic effects as well as antioxidant effects. We therefore investigated whether EC could prevent METH-induced neurotoxicity using HT22 hippocampal neuronal cells. EC reduced METH-induced cell death of HT22 cells. In addition, we observed that EC abrogated the activation of ERK, p38 and inhibited the expression of CHOP and DR4. EC also reduced METH-induced ROS accumulation and MMP. These results suggest that EC may protect HT22 hippocampal neurons against METH-induced cell death by reducing ER stress and mitochondrial damage.

Metabolic syndrome: prevalence and risk factors in Korean gout patients

BACKGROUND/AIMS: We performed this study to investigate associations between metabolic syndrome, chronic kidney disease (CKD), and gout. METHODS: We reviewed the medical records of 151 patients with gout at the Department of Rheumatology in Korea University Ansan Hospital. The following measures were examined: waist circumference, blood pressure, alcohol consumption, and levels of triglyceride, high density lipoprotein cholesterol, fasting serum glucose, serum uric acid (SUA), creatinine, insulin, and C-peptide. We assessed metabolic syndrome by the homeostasis model assessment of insulin resistance (HOMA-IR) index and renal function by the Modification of Diet in Renal Disease equation; patients were classified according to World Health Organization Asia-Pacific obesity criteria. RESULTS: The prevalence of metabolic syndrome in gout patients (50.8%) was higher than in non-gout patients. The mean SUA level was significantly higher in gout patients with metabolic syndrome (9.13 ± 3.15 mg/dL) than in gout patients without metabolic syndrome (8.14 ± 2.07 mg/dL). The mean SUA level was also significantly higher in patients with gout and CKD (9.55 ± 2.86 mg/dL) than in patients with gout but no CKD (7.74 ± 2.27 mg/dL). In gout patients, HOMA-IR was positively correlated with waist circumference (r = 0.409, p = 0.001). CONCLUSIONS: The prevalence of metabolic syndrome in patients with gout was 50.8%, which is higher than the prevalence in the general Korean population. Hyperuricemia in gout patients was correlated with metabolic syndrome and CKD. Insulin resistance may provide clues to better understand the relationship between metabolic syndrome, CKD, and gout.

Repeated gastric dilatations leading to fatal abdominal compartment syndrome in a patient with bulimia nervosa

Cases of repeated acute gastric dilatations after binge eating in one patient are rarely reported. We report here a case of repeated acute gastric dilatations in a 22-year-old woman with bulimia nervosa. Her repeated acute gastric dilatations seem to have been related to superior mesenteric artery syndrome. On her last visit due to acute gastric dilatation, she underwent emergency gastric decompression surgery because of abdominal compartment syndrome; however, she eventually died because of ischemia reperfusion injury. Emergency physicians should be aware of the need to manage acute gastric dilatation in patients with eating disorder and should pay attention to the signs and distinctive clinical features of abdominal compartment syndrome.

Comparison of Synchronous and Metachronous Primary Carcinomas of the Bladder and Prostate

PURPOSE: The incidence of multiple primary malignant neoplasms increases with age. An unforeseen finding is the high number of prostate and bladder cancers pairs. Of prostate and bladder cancers pair as first primary and second primary cancers and vice versa, we investigated the differences in clinicopathological features between synchronous and metachronous primary carcinomas of the bladder and prostate. MATERIALS AND METHODS: Fifty-three patients diagnosed with dual prostate and bladder cancer in a 12-year period (2004–2015) excluding cases with incidental prostate cancer after radical cystectomy were reviewed. Enrolled patients were divided into 3 groups according to cancer development (group I, synchronous cancer; group II, prostate cancer with metachronous bladder cancer; group III, bladder cancer with metachronous prostate cancer). Each group was compared according to clinicopathological features. RESULTS: Median age was 72 years (range, 54–83 years). Groups I, II, and III comprised 29 (54.7%), 8 (15.1%), and 16 patients (30.2%), respectively. Age, prostate-specific antigen, tumor stage, grade, multifocality of bladder tumor, and treatment modality did not show statistical differences between groups. However, group III showed a lower prostate cancer stage (National Comprehensive Cancer Network anatomic stage; p=0.009) and had low-risk of prostate cancers (p=0.025). CONCLUSIONS: Bladder tumor showed no differences in the clinicopathological features between synchronous and metachronous primary carcinomas. However, metachronous prostate cancer showed better clinicopathological features of prostate cancer. It is important for clinicians to counselling and decision making in clinical situations

Panenteritis as an Initial Presentation of Systemic Lupus Erythematosus / 대한소화기학회지

Lupus enteritis is a rare, severe complication of systemic lupus erythematosus (SLE), needing prompt diagnosis and proper management. However, SLE rarely presents as lupus enteritis at the time of initial diagnosis. Thus, delayed diagnosis and misdiagnosis are common. We report a case of a 25-year-old woman with lupus panenteritis. The patient had multiple hospitalizations for abdominal pain, nausea, and diarrhea, initially without any other symptoms suggestive of SLE, but was later observed to have malar rash and oral ulcers. Laboratory investigations were compatible with SLE, including positive antinuclear antibody (1:320) with speckled pattern. CT revealed diffuse hypodense submucosal thickening of the stomach, the entire small bowel, colon, appendix, and rectum. Treatment with high-dose corticosteroids followed by maintenance therapy with mycophenolate mofetil, hydroxychloroquine, and azathioprine resulted in clinical improvement. Diagnosis of lupus enteritis requires a high index of suspicion given the low incidence and nonspecific clinical findings.

The Clinical Features and Helicobacter pylori Eradication Therapy in Lymphofollicular Gastritis: A Single Center Experience

BACKGROUND/AIMS: Lymphofollicular gastritis (LFG) is defined as antral gastritis with endoscopic findings characterized by a miliary pattern resembling “goose flesh”. We aimed to analyze the clinical features of LFG and the utility of Helicobacter pylori eradication therapy in LFG. MATERIALS AND METHODS: Patients with LFG, regardless of upper gastrointestinal symptoms (7 men, 28 women; age range, 21~67 years), were examined for H. pylori using the CLO test during endoscopy. One specimen was obtained from the greater curvatures of the lower body and the antrum. Clinical features were compared according to H. pylori-positive status. RESULTS: Among 35 patients with LFG, 31 (88.6%) were infected with H. pylori. LFG predominantly affected young women (28/35, 80.0%; mean age, 43.73 years). One case of gastric cancer with H. pylori-positive LFG was found. H. pylori eradication rate in LFG patients was low (3/12, 25.0%). CONCLUSIONS: LFG is closely associated with H. pylori infection and predominantly affects women and young adults. Future studies are needed to determine whether H. pylori eradication reduces the risk of gastric cancer.

A Case of Non-Hodgkin's Lymphoma of the Ocular Adnexa and Lung in a 17-year-old with Primary Sjogren's Syndrome

Sjogren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocyte-mediated destruction of exocrine glands, which produces classical symptoms of dry eyes and dry mouth. Aside from the clinical manifestations associated with exocrine glands, extraglandular features of SS include a major long-term concern for development of lymphoma. The lifetime risk of non-Hodgkin's lymphoma (NHL) in an SS patient is approximately 5% to 10%, 20 times higher than that of the normal population. This case report describes a rare occurrence of NHL in the eyelid and lung of an adolescent female with SS, whose disease activity had been monitored closely. This is the first reported case in Korea.

A Case of an Accessory Cystic Duct Draining into the Right Intrahepatic Duct / 대한췌담도학회지

Anatomic variations in the biliary tree may not be detected until adulthood and they can cause unexplained jaundice and biliary pain. Recognition of these anatomic variations is important to avoid an incorrect diagnosis and significant ductal injury during biliary surgery. Although there are numerous anatomic bile duct variations, an accessory cystic duct draining into the right hepatic duct is rare. We report a case of an accessory cystic duct draining into the right hepatic duct with cholelithiasis, in which the abnormality was identified by endoscopic retrograde cholangiopancreatography and magnetic resonance cholangiopancreatography and confirmed by laparoscopic cholecystectomy.

In Vitro Antifungal Activity and Mode of Action of 2',4'-Dihydroxychalcone against Aspergillus fumigatus

2',4'-Dihydroxychalcone (2',4'-DHC) was identified from a heat shock protein 90 (Hsp90)-targeting library as a compound with Hsp90 inhibitory and antifungal effects. In the presence of 2',4'-DHC (8 microg/mL), radial growth of Aspergillus fumigatus was inhibited 20% compared to the control, and green pigmentation was completely blocked. The expression of the conidiation-associated genes abaA, brlA, and wetA was significantly decreased (approximately 3- to 5-fold) by treatment with 2',4'-DHC. The expression of calcineurin signaling components, cnaA and crzA, was also significantly reduced. The inhibitory effects of 2',4'-DHC on metabolic activity and mycelial growth were significantly enhanced by combination treatment with itraconazole and caspofungin. Docking studies indicated that 2',4'-DHC bind to the ATPase domain of Hsp90. These results suggest that 2',4'-DHC act as an Hsp90-calcinurin pathway inhibitor.

Avascular Necrosis of the Femoral Head in Patient Visiting for Abdominal Pain / 이화의대지

No abstract available.

Small Molecule Inhibitors to Disrupt Protein-protein Interactions of Heat Shock Protein 90 Chaperone Machinery

Heat shock protein 90 (Hsp90) is an adenosine triphosphate dependent molecular chaperone in eukaryotic cells that regulates the activation and maintenance of numerous regulatory and signaling proteins including epidermal growth factor receptor, human epidermal growth factor receptor 2, mesenchymal-epithelial transition factor, cyclin-dependent kinase-4, protein kinase B, hypoxia-inducible factor 1alpha, and matrix metalloproteinase-2. Since many of Hsp90 clients are oncogenic proteins, Hsp90 has become an attractive therapeutic target for treatment of cancer. To discover small molecule inhibitors targeting Hsp90 chaperone machinery, several strategies have been employed, which results in three classes of inhibitors such as N-terminal inhibitors, C-terminal inhibitors, and inhibitors disrupting protein-protein interactions of Hsp90 chaperone machinery. Developing small molecule inhibitors that modulate protein-protein interactions of Hsp90 is a challenging task, although it offers many alternative opportunities for therapeutic intervention. The lack of well-defined binding pocket and starting points for drug design challenges medicinal chemists to discover small molecule inhibitors disrupting protein-protein interactions of Hsp90. The present review will focus on the current studies on small molecule inhibitors disrupting protein-protein interactions of Hsp90 chaperone machinery, provide biological background on the structure, function and mechanism of Hsp90's protein-protein interactions, and discuss the challenges and promise of its small molecule modulations.

Dual Inhibitors Against Topoisomerases and Histone Deacetylases

Topoisomerases and histone deacetylases (HDACs) are considered as important therapeutic targets for a wide range of cancers, due to their association with the initiation, proliferation and survival of cancer cells. Topoisomerases are involved in the cleavage and religation processes of DNA, while HDACs regulate a dynamic epigenetic modification of the lysine amino acid on various proteins. Extensive studies have been undertaken to discover small molecule inhibitor of each protein and thereby, several drugs have been transpired from this effort and successfully approved for clinical use. However, the inherent heterogeneity and multiple genetic abnormalities of cancers challenge the clinical application of these single targeted drugs. In order to overcome the limitations of a single target approach, a novel approach, simultaneously targeting topoisomerases and HDACs with a single molecule has been recently employed and attracted much attention of medicinal chemists in drug discovery. This review highlights the current studies on the discovery of dual inhibitors against topoisomerases and HDACs, provides their pharmacological aspects and advantages, and discusses the challenges and promise of the dual inhibitors.

Predictors of Intravesical Recurrence After Radical Nephroureterectomy for Upper Urinary Tract Urothelial Carcinoma: An Inflammation-Based Prognostic Score

PURPOSE: Systemic inflammatory responses, which are defined in terms of the Glasgow prognostic score (GPS), have been reported to be independent predictors of unfavorable outcomes in various human cancers. We assessed the utility of the GPS as a predictor of intravesical recurrence after radical nephroureterectomy (RNU) in upper urinary tract carcinoma (UTUC). MATERIALS AND METHODS: We collected data for 147 UTUC patients with no previous history of bladder cancer who underwent RNU from 2004 to 2012. Associations between perioperative clinicopathological variables and intravesical recurrence were analyzed by using univariate and multivariate Cox regression models. RESULTS: Overall, 71 of 147 patients (48%) developed intravesical recurrence, including 21 patients (30%) diagnosed with synchronous bladder tumor. In the univariate analysis, performance status, diabetes mellitus (DM), serum albumin, C-reactive protein, GPS, and synchronous bladder tumor were associated with intravesical recurrence. In the multivariate analysis, performance status (hazard ratio [HR], 2.33; 95% confidence interval [CI], 1.41-3.85; p=0.001), DM (HR, 2.04; 95% CI, 1.21-3.41; p=0.007), cortical thinning (HR, 2.01; 95% CI, 1.08-3.71; p=0.026), and GPS (score of 1: HR, 6.86; 95% CI, 3.69-12.7; p=0.001; score of 2: HR, 5.96; 95% CI, 3.10-11.4; p=0.001) were independent predictors of intravesical recurrence. CONCLUSIONS: Our results suggest that the GPS as well as performance status, DM, and cortical thinning are associated with intravesical recurrence after RNU. Thus, more careful follow-up, coupled with postoperative intravesical therapy to avoid bladder recurrence, should be considered in these patients.

Recurrent Pneumothorax after Etanercept Therapy in a Rheumatoid Arthritis Patient: A Case Report / 전남의대학술지

The use of anti-tumor necrosis factor (anti-TNF) agents for rheumatoid arthritis (RA) patients who are refractory to disease-modifying anti-rheumatic drugs is gradually increasing. Etanercept is the first anti-TNF agent to be approved for RA treatment and is also the most widely used. However, aggravation of interstitial lung disease after etanercept treatment in RA patients has been reported recently. We report the first case of recurrent spontaneous pneumothorax with progression of interstitial lung disease after initiating etanercept therapy. The withdrawal of etanercept and a change to adalimumab, a different class of TNF inhibitor, achieved clinical stabilization.

Leflunomide-induced Toxic Epidermal Necrolysis in a Patient with Rheumatoid Arthritis

Leflunomide was licensed for the treatment of rheumatoid arthritis in 1998 and has been available in Korea since 2003. Allergic cutaneous reactions (rash, purpura) are common (<10%) side effects of leflunomide, but severe cases such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) are rarely reported. There has not been a report of SJS or TEN induced by leflunomide in Korea. Here we report a case of leflunomide-induced TEN in a patient with rheumatoid arthritis. Leflunomide was discontinued, and the TEN was treated with methylprednisolone, cholestyramine and immunoglobulin. The skin lesion eventually resolved over four weeks with residual post-inflammatory hyperpigmentation.

Vitamin D Levels in Children and Adolescents with Antiepileptic Drug Treatment

PURPOSE: This study was to evaluate the relationship of 25(OH)D3 levels with anticonvulsant use and other possible factors in epileptic children and adolescents. MATERIALS AND METHODS: We studied 143 patients with epilepsy (90 boys, 53 girls; 11.21+/-4.49 years), who had been treated with anticonvulsants for more than 1 year. Patients who had taken multiple vitamins before the blood test and those who have the limitation of physical activity (wheelchair-bound) were excluded from the study. We evaluated the difference in vitamin D status according to the type and number of anticonvulsants taken and other factors such as gender, age, intelligence and seizure variables. RESULTS: For patients with mental retardation or developmental delay, 25(OH)D3 levels were lower than the levels in patients with normal intelligence quotient levels (p=0.03). 25(OH)D3 levels were lower in patients who had taken anticonvulsants for more than 2 years as compared to those who had taken them for less than 2 years (p=0.03). Those taking oxcarbazepine had significantly lower vitamin D levels than patients taking valproic acid (p=0.01). However, no effects of number of anticonvulsants taken were detectable. More than two-thirds of the patients were diagnosed with osteopenia or osteoporosis in patients showing either vitamin D insufficiency or deficiency. CONCLUSION: The possibility of vitamin D deficiency can be considered in pediatric patients taking anticonvulsants if they have mental retardation or developmental delay or if they have been taking anticonvulsants for more than 2 years or taking hepatic enzyme inducing drugs.

Predictive value of C-reactive protein in response to macrolides in children with macrolide-resistant Mycoplasma pneumoniae pneumonia / 소아과

PURPOSE: The prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) has increased worldwide. The aim of this study was to estimate the proportion of MRMP in a tertiary hospital in Korea, and to find potential laboratory markers that could be used to predict the efficacy of macrolides in children with MRMP pneumonia. METHODS: A total of 95 patients with M. pneumoniae pneumonia were enrolled in this study. Detection of MRMP was based on the results of specific point mutations in domain V of the 23S rRNA gene. The medical records of these patients were reviewed retrospectively and the clinical course and laboratory data were compared. RESULTS: The proportion of patients with MRMP was 51.6% and all MRMP isolates had the A2063G point mutation. The MRMP group had longer hospital stay and febrile period after initiation of macrolides. The levels of serum C-reactive protein (CRP) and interleukin-18 in nasopharyngeal aspirate were significantly higher in patients who did not respond to macrolide treatment. CRP was the only significant factor in predicting the efficacy of macrolides in patients with MRMP pneumonia. The area under the curve for CRP was 0.69 in receiver operating characteristic curve analysis, indicating reasonable discriminative power, and the optimal cutoff value was 40.7 mg/L. CONCLUSION: The proportion of patients with MRMP was high, suggesting that the prevalence of MRMP is rising rapidly in Korea. Serum CRP could be a useful marker for predicting the efficacy of macrolides and helping clinicians make better clinical decisions in children with MRMP pneumonia.