Objective: Parametrial tissue ligation during total laparoscopic hysterectomy (TLH) is important in large uteri with large vessels. Methods: A retrospective study was performed at Asan Medical Center for comparing TLH performed with a new knotless parametrial tissue ligation method and conventional laparoscopic-assisted vaginal hysterectomy (LAVH) from March 2019 to August 2021. For TLH, after anterior colpotomy, the parametrial tissue was ligated by anchoring the suture and making a loop in one direction three times using 1-0 V-LocTM 180 (Covidien, Mansfield, MA, USA) suture. Subsequently, the cranial part of the loop was cut using an endoscopic device. Results: A total of 119 and 178 patients were included in the TLH and LAVH groups, respectively. The maximal diameter of the uterus was larger in the TLH group (106.29±27.16 cm) than in the LAVH group (99.00±18.92 cm, P=0.01). The change in hemoglobin (Hb) level was greater in the LAVH group than in the TLH group (P<0.001). The weight of the removed uterus was greater in the TLH group than in the LAVH group (431.95±394.97 vs. 354.94±209.52 g; P=0.03). However, when the uterine weight was >1,000 g, the operative times and change in Hb levels were similar between the two groups. In both groups, no ureteral complications occurred during or after surgery. Conclusion Knotless parametrial tissue ligation using 1-0 V-LocTM 180 suture in TLH can be safely applied, even in cases with large uteri, without increased risks of ureteral injury or uterine bleeding.

Several medications are approved to treat coronavirus disease 2019 (COVID-19) in Korea including nirmatrelvir/ritonavir, remdesivir, and regdanvimab. There is potential drug-drug interaction between antiepileptic drugs (AEDs) and the medications used to treat COVID-19. Several AEDs such as phenytoin, carbamazepine, phenobarbital, and primidone are strong cytochrome P450 inducers and can inhibit the drugs used for COVID-19. Particularly, these drugs are contraindicated with nirmatrelvir/ritonavir (Paxlovid®). There is a weaker drug-drug interaction between the AEDs and remdesivir. No significant interaction has been reported between the AEDs and molnupiravir. Pharmacokinetic interactions of the AEDs are important in effective management of COVID-19 in patients with epilepsy.

Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. Methods: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. Results: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. Conclusion CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

Background: Obstructive sleep apnea (OSA) is associated with pulmonary fibrosis. Chronic intermittent hypoxia (CIH) is considered to be a surrogate of OSA. However, its exact role in pulmonary fibrosis remains uncertain. Therefore, we investigated the mechanism underlying CIH-induced pulmonary fibrosis and the role of the anti-fibrotic agent in bleomycin (BLE) induced lung injury. Methods: Mice were divided into eight groups: the normoxia (NOR), CIH, NOR plus BLE, CIH plus BLE, NOR plus pirfenidone (PF), CIH plus PF, NOR plus BLE and PF, and CIH plus BLE and PF groups. BLE was administered intratracheally on day 14 following CIH or NOR exposure. Subsequently, the mice were exposed to CIH or NOR for an additional 4 weeks. PF was administered orally on day 5 after BLE instillation once daily for 3 weeks. Results: In the BLE-treated groups, CIH-induced more collagen deposition in lung tissues than NOR, and significantly increased hydroxyproline and transforming growth factor-β expression. The CIH and BLE-treated groups showed increased lung inflammation compared to NOR or CIH groups. Following CIH with BLE treatment, nuclear factor-κB (NF-κB) protein expression was significantly increased, whereas nuclear factor-erythroid-related factor 2 (Nrf2) and heme oxygenase-1 protein levels were decreased. After PF treatment, NF-κB and Kelch-like ECH-associated protein 1 expression were suppressed, and Nrf2 expression was increased. Conclusion CIH accelerated lung fibrosis in BLE-induced lung injury in mice, potentially by regulating the NF-κB/Nrf2 signaling pathway. Our results implicate PF as a potential therapeutic agent for treating pulmonary fibrosis in individuals with OSA and idiopathic pulmonary fibrosis.

Background: Lightwand is a convenient tool that can be used instead of a laryngoscope for intubation. Tracheal intubation causes direct stimulation of the larynx, drastically increasing hemodynamic values including blood pressure and heart rate. This study aims to identify the effect of different doses of esmolol on hemodynamic changes during lightwand intubation. Methods: The study subjects included 140 patients who underwent general anesthesia for elective surgery. The patients were randomly divided into four groups (35 patients in each group). The ‘C’ group only received 20 ml of normal saline, while the ‘E0.5’, ‘E1’, and ‘E2’ groups received 20 ml of normal saline containing esmolol—0.5 mg/kg, 1 mg/kg, and 2 mg/kg, respectively, injected 2 min prior to intubation. The patients’ blood pressure, heart rate, and rate-pressure product were measured six times, before and after the intubation. Results: The degree of heart rate elevation was suppressed in the E1 and E2 groups compared to the C group, and RPP after intubation significantly decreased in the E2 group compared to the C group. Conclusions 1–2 mg/kg of a single esmolol injection prior to lightwand intubation effectively blunts heart rate elevation, and 2 mg/kg of esmolol injection blunts rate-pressure product elevation.

Econazole, a potent broad-spectrum antifungal agent and a Ca2+ channel antagonist, induces cytotoxicity in leukemia cells and is used for the treatment of skin infections. However, little is known about its cytotoxic effects on solid tumor cells. Here, we investigated the molecular mechanism underlying econazole-induced toxicity in vitro and evaluated its regulatory effect on the metastasis of gastric cancer cells. Using the gastric cancer cell lines AGS and SNU1 expressing wild-type p53 we demonstrated that econazole could significantly reduce cell viability and colony-forming (tumorigenesis) ability. Econazole induced G0/G1 phase arrest, promoted apoptosis, and effectively blocked proliferation- and survival-related signal transduction pathways in gastric cancer cells. In addition, econazole inhibited the secretion of matrix metalloproteinase- 2 (MMP-2) and MMP-9, which degrade the extracellular matrix and basement membrane. Econazole also effectively inhibited the metastasis of gastric cancer cells, as confirmed from cell invasion and wound healing assays. The protein level of p53 was significantly elevated after econazole treatment of AGS and SNU1 cells. However, apoptosis was blocked in econazole-treated cells exposed to a p53-specific small-interfering RNA to eliminate p53 expression. These results provide evidence that econazole could be repurposed to induce gastric cancer cell death and inhibit cancer invasion.

It is difficult to differentiate acute skin failure (ASF) from pressure ulcer (PU). ASF is defined as unavoidable injury resulting from hypoperfusion caused by severe dysfunction of another organ system. We describe a case of ASF mistaken as PU that resulted in a legal dispute. A 74-year-old male patient was admitted to our intensive care unit with sepsis due to bacterial pneumonia. Despite the use of air cushions and regular position changes, skin ulcerations occurred over his occiput, back, buttock, elbow, and ankle. After improvement in his general condition, he was transferred to the department of plastic and reconstructive surgery. Debridement was performed immediately, followed by conservative treatment (including a vacuum-assisted closure device) for 6 weeks. The buttock and occiput wounds were treated surgically. Despite complete healing, his caregivers sued the hospital for failing to prevent PU formation. ASF is a pressure-related injury resulting from hemodynamic instability due to organ system failure. Unlike PU, ASF may occur despite the implementation of all appropriate preventive measures. Furthermore, misdiagnosis of ASF as PU can lead to litigation. Therefore, it is critical for the proper diagnosis to be made quickly, and for physicians to explain that ASF occurs despite proper preventative treatment.
Aged ; Ankle ; Buttocks ; Caregivers ; Debridement ; Diagnosis ; Diagnostic Errors ; Dissent and Disputes ; Elbow ; Hemodynamics ; Humans ; Intensive Care Units ; Jurisprudence ; Male ; Necrosis ; Negative-Pressure Wound Therapy ; Plastics ; Pneumonia, Bacterial ; Pressure Ulcer ; Sepsis ; Skin Ulcer ; Skin ; Wounds and Injuries

PURPOSE: Although severe cutaneous adverse drug reactions (SCARs) are rare, they are associated with high morbidity and mortality, and thus early diagnosis and treatment are critical for improving prognoses. However, few studies have reported the characteristics of SCARs in children. Thus, we aimed to evaluate the clinical characteristics, current management and prognosis of pediatric SCARs. METHODS: We analyzed pediatric data in the Korean SCARs registry, which was built retrospectively in 2016 with SCAR cases treated in 34 tertiary referral university hospitals during 2010–2015. Using these cases, we descriptively analyzed detailed data regarding etiology, clinical and laboratory features, treatment strategies, and prognosis. RESULTS: Forty-seven pediatric SCAR cases from 15 tertiary referral hospitals were included. The median patient age was 10 (interquartile range, 3-15.5) years and 68.1% (n = 32) were males. The culprit drug was identified in 95.7% (n = 45) of the patients; antibiotics (44.7%) and antiepileptic drugs (19.1%) were the most common and second most common culprits, respectively. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) cases presented with the largest area of skin involvement without permanent sequelae. Stevens-Johnson syndrome (SJS) cases involved relatively small areas of skin but serious sequelae in two children. Of 4 patients with toxic epidermal necrolysis (TEN), 1 died. Of all patients assessed, 36 (76.6%) received systemic steroids and 21 (44.7%) received intravenous immunoglobulin (IVIG). Thirteen (27.7%) received both systemic steroids and IVIG. Cyclosporine was administered to only 1 patient along with a systemic steroid. CONCLUSIONS: In patients with pediatric SCARs, including those with DRESS, SJS and TEN, clinical presentations were variable. Thus, there was no clear continuous disease spectrum. Although the mortality rate was low (2.1%), clinical suspicion may be the best tool for proactive SCAR management.
Anti-Bacterial Agents ; Anticonvulsants ; Child ; Cicatrix ; Cyclosporine ; Drug Eruptions ; Drug Hypersensitivity Syndrome ; Drug-Related Side Effects and Adverse Reactions ; Early Diagnosis ; Hospitals, University ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Korea ; Male ; Mortality ; Prognosis ; Referral and Consultation ; Retrospective Studies ; Skin ; Steroids ; Stevens-Johnson Syndrome ; Tertiary Care Centers

PURPOSE: Although the DTaP and Tdap vaccines used to prevent pertussis have been used for a long time, there is no standard method for measuring pertussis antigens. Therefore, this preliminary study was conducted to develop an enzyme-linked immunosorbent assay method using an animal model for measuring antibodies against pertussis toxin, the most important pertussis pathogenic antigen, in the sera of vaccinated mice. MATERIALS AND METHODS: Bordetella pertussis Tohama phase I was cultured for 24–30 hours, and then pertussis toxin was purified from the culture medium by chromatography. Purified pertussis toxin was diluted in phosphate-buffered saline-coating buffer, and 100 µL of diluted pertussis toxin was added to each well and reacted at room temperature for 4 hours. Positive serum was diluted to 1/1,250–1/80,000 and negative serum was diluted to 1/50 to determine the coating concentration with the optimal signal/noise ratio. Optimal test conditions were confirmed from the dilution factors of the secondary antibody and streptavidin horseradish peroxidase (SA-HRP). RESULTS: Optimal conditions were as follows: 4 µg/mL for coating antigen; 1/40,000 for secondary antibody; and 1/1,000 for the SA-HRP dilution factor. Comparison of the sera obtained from mice treated with a developing vaccine and commercial vaccine with National Institute for Biological Standard and Control standard serum under the established conditions showed the following results: 1,300.62, 534.94, and 34.85, respectively. CONCLUSION: The method developed in this study is suitable for measuring anti-pertussis toxin antibodies and may be applicable for clinical sample analysis or indirect diagnosis of pertussis.
Animals ; Antibodies ; Bordetella pertussis ; Chromatography ; Diagnosis ; Enzyme-Linked Immunosorbent Assay* ; Horseradish Peroxidase ; Methods ; Mice* ; Models, Animal ; Pertussis Toxin ; Streptavidin ; Vaccines ; Whooping Cough

PURPOSE: We aimed to determine the prognostic significance of lymphocyte counts and the lymphocytemonocyte ratio (LMR) in pediatric patients with osteosarcoma. METHODS: We retrospectively reviewed the medical records of 27 pediatric patients with localized extremity osteosarcoma, treated at the Korea Cancer Center Hospital between May 2002 and March 2016. Leukocyte counts and LMR before treatment and on day 14 (LMR14) of the first cisplatin-doxorubicin chemotherapy round were evaluated. Patients were dichotomized according to the median value of these parameters, and survival rates were compared. RESULTS: The median age of the 27 patients was 9.9 years (range, 3.2–14.1 years) and tumor sites were: distal femur (n=14), proximal humerus (n=7), proximal tibia (n=2), proximal fibula (n=2), and elsewhere (n=2). Patients were followed up on for a median of 76.4 months (range, 4.5–174.7 months), and 5-year overall (OS) and event-free survival (EFS) rates were 66.0%±9.8% and 60.9%±9.7%, respectively. Patients with a higher pretreatment lymphocyte count (≥2,320/μL) had better OS (90.9% vs. 46.2%, P=0.04) and EFS (83.9% vs. 38.5%, P=0.02). However, the day 14 lymphocyte count was not associated with survival. While no survival difference was observed between patients grouped according to pretreatment LMR (median value, 6.3), patients with a higher LMR14 (≥5) fared better than those with lower LMR14 (5-year OS: 83.3% vs. 46.3%, P=0.04). CONCLUSION: Pretreatment lymphocyte count and LMR during chemotherapy had prognostic significance in pediatric osteosarcoma patients. Further studies involving larger cohorts are necessary to validate our findings.
Cohort Studies ; Disease-Free Survival ; Drug Therapy ; Extremities ; Femur ; Fibula ; Humans ; Humerus ; Korea ; Leukocyte Count ; Lymphocyte Count ; Lymphocytes ; Medical Records ; Monocytes ; Osteosarcoma ; Retrospective Studies ; Survival Rate ; Tibia ; Treatment Outcome