Background: During coronavirus disease 2019 (COVID-19) pandemic, several COVID-19 vaccines were licensed with fast-track procedures. Although these vaccines have demonstrated high immunogenicity, there has been concerns on the serious adverse events (AEs) following COVID-19 vaccination among adolescents. We aimed to analyze comparative safety of COVID-19 vaccination in adolescents. Methods: In this pharmacovigilance study, we performed a disproportionality analysis using VigiBase, the World Health Organization’s global individual case safety report (ICSR) database. To compare serious AEs reported following COVID-19 vaccines vs. all other vaccines in adolescents aged 12–17 years, ICSRs following any vaccines on adolescents aged 12–17 years were included, defining cases as reports with the AEs of interest, with all other AEs as non-cases. The AEs of interest were myocarditis/pericarditis, multisystem inflammatory syndrome/Kawasaki disease (MIS/KD), anaphylaxis, Guillain-Barré syndrome (GBS), and immune thrombocytopenia (ITP). We conducted a disproportionality analysis to estimate reporting odds ratio (ROR) with 95% confidence interval (CI) for each AE of interest, adjusted for sex by using logistic regression. Results: Of 99,735 AE reports after vaccination in adolescents, 80,018 reports were from COVID-19 vaccinated adolescents (52.9% females; 56.3% America). The AEs of interest were predominantly reported as serious AE (76.1%) with mRNA vaccines (99.4%). Generally, higher reporting odds for the AEs were identified following COVID-19 vaccination in adolescents;myocarditis/pericarditis (2,829 reports for the COVID-19 vaccine vs. 35 for all other vaccines, adjusted ROR [aROR], 19.61; 95% CI, 14.05–27.39), and MIS/KD (104 vs. 6, aROR, 4.33; 95% CI, 1.89–9.88). The reporting odds for anaphylaxis (515 vs. 165, aROR, 0.86; 95% CI, 0.72– 1.02), GBS (94 vs. 40, aROR, 0.64; 95% CI, 0.44–0.92) and ITP (52 vs. 12, aROR, 1.12; 95% CI, 0.59–2.09) were not significantly higher following COVID-19 vaccination. Conclusion In this study, there were disproportionate reporting of immune-related AEs following COVID-19 vaccination. While awaiting definitive evidence, there is a need to closely monitor for any signs of immune-related AEs following COVID-19 vaccination among adolescents.

Background: There is a need to update the cardiovascular (CV) Sequential Organ Failure Assessment (SOFA) score to reflect the current practice in sepsis. We previously proposed the modified CV SOFA score from data on blood pressure, norepinephrine equivalent dose, and lactate as gathered from emergency departments. In this study, we externally validated the modified CV SOFA score in multicenter intensive care unit (ICU) patients. Methods: A multicenter retrospective observational study was conducted on ICU patients at six hospitals in Korea. We included adult patients with sepsis who were admitted to ICUs. We compared the prognostic performance of the modified CV/total SOFA score and the original CV/total SOFA score in predicting 28-day mortality. Discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUROC) and the calibration curve, respectively. Results: We analyzed 1,015 ICU patients with sepsis. In overall patients, the 28-day mortality rate was 31.2%. The predictive validity of the modified CV SOFA (AUROC, 0.712; 95% confidence interval [CI], 0.677–0.746; P < 0.001) was significantly higher than that of the original CV SOFA (AUROC, 0.644; 95% CI, 0.611–0.677). The predictive validity of modified total SOFA score for 28-day mortality was significantly higher than that of the original total SOFA (AUROC, 0.747 vs. 0.730; 95% CI, 0.715–0.779; P = 0.002). The calibration curve of the original CV SOFA for 28-day mortality showed poor calibration. In contrast, the calibration curve of the modified CV SOFA for 28-day mortality showed good calibration. Conclusion In patients with sepsis in the ICU, the modified SOFA score performed better than the original SOFA score in predicting 28-day mortality.

Background: Three-dimensional (3D)-printed customized implants can be fabricated and utilized for all bones with massive bone defects. The main safety issues with 3D-printed implants made of Ti6Al4V alloy are related to the release of metal debris and residual powder. In this study, we investigated the perioperative titanium concentrations in whole blood and peri-implant fluid samples of patients who underwent limb salvage surgery with a 3D-printed Ti6Al4V implant. Methods: Nineteen patients who underwent limb salvage surgery with 3D-printed Ti6Al4V implants were divided into two groups:the serial samples group and the follow-up group. To observe metal distribution and clearance in the body, serial samples of blood and peri-implant fluid from the surgical drain were prospectively collected for five patients in the serial samples group. For the remaining 14 patients who were followed up for more than a year, blood samples were collected only once. Results: In the serial samples group, the mean baseline titanium concentration was 0.78 μg/L (range, 0.1–2.2 μg/L): 3 patients showed peak concentration before the third postoperative month, while 2 patients still showed an increasing pattern at this point.Total titanium mass in the surgical drain showed a wash-out phenomenon in a week, with a significant uniform decrease (p = 0.04).In 14 patients in the follow-up group, the mean titanium concentration in the whole blood was 10.8 μg/L (range, 0.3–36.6 μg/L). For the 14 patients with a long-term follow-up, the aluminum and vanadium concentrations were all negligible. Conclusions Whole blood titanium concentrations were higher after surgery using 3D-printed implants than after that using conventional orthopedic implants, but markedly lower than in patients with implant failure. None of the patients developed serious clinical adverse effects during follow-up.

Purpose: Due to low incidence, epidemiologic data of Ewing sarcoma in the Asian population are scarce. We aimed to examine the incidence pattern and outcome of patients with Ewing sarcoma in the Republic of Korea. Materials and Methods: Data of patients with Ewing sarcoma diagnosed between 1999 and 2017 were obtained from the Korea Central Cancer Registry (KCCR). Incidence, clinical characteristics, and survival rates were analyzed and compared between different age groups. Results: There were 788 cases (459 males, 329 females), with a median age at diagnosis of 20 years. The age-standardized rate of Ewing sarcoma was 1.01. The number of cases and incidence rates in each age group were as follows: children, 1.6; adolescents and young adults (AYA), 0.93; adults, 0.44; and elderly, 0.53. There were more male cases in children and the AYA group (p < 0.001). Extraskeletal tumors (p < 0.001), primary sites other than extremity (p=0.007), and presence of metastasis at diagnosis (p=0.031) were more frequent in the adults and elderly group. With a median survival time of 78 months, the 5-year overall survival (OS) rate of the entire cohort was 52%. Children fared best (5-year OS, 75%), and the 5-year OS of AYA patients (51%) approximated the OS of the entire cohort. A two-fold difference of 5-year OS was observed between adults and elderly patients (42% vs. 19%). On univariate and multivariate analyses, age ≥ 15 years and presence of metastasis were adverse prognostic factors. Conclusion This was the first epidemiologic study of Ewing sarcoma using the KCCR data. With a similar incidence to other Asian countries, the survival rate was slightly lower than that of Euro-American cases. Collaborative clinical studies are necessary to improve the outcome of Ewing sarcoma in low-incidence populations.

Purpose: No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults. Materials and Methods: We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m2 intravenously on day 1, irinotecan, 50 mg/m2/day intravenously on days 1-5, and temozolomide, 100 mg/m2/day orally on days 1-5. Results: A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality. Conclusion The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.

Purpose: Bladder capacity is an important parameter in the diagnosis of lower urinary tract dysfunction. We aimed to determine whether the maximum bladder capacity (MCC) measured during a urodynamic study was affected by involuntary detrusor contraction (IDC) in patients with Lower Urinary Tract Symptoms (LUTS)/Benign Prostatic Hyperplasia (BPH). Methods: Between March 2020 and April 2021, we obtained maximum voided volume (MVV) from a 3-day frequency-volume chart, MCC during filling cystometry, and maximum anesthetic bladder capacity (MABC) during holmium laser enucleation of the prostate under spinal or general anesthesia in 139 men with LUTS/BPH aged >50 years. Patients were divided according to the presence of IDC during filling cystometry. We assumed that the MABC is close to the true value of the MCC, as it is measured under the condition of minimizing neural influence over the bladder. Results: There was no difference in demographic and clinical characteristics between the non-IDC (n=20) and IDC groups (n=119) (mean age, 71.5±7.4) (P>0.05). The non-IDC group had greater bladder volume to feel the first sensation, first desire, and strong desire than the IDC group (P<0.001). In all patients, MABC and MVV were correlated (r=0.41, P<0.001); however, there was no correlation between MCC and MABC (r=0.19, P=0.02). There was no significant difference in MABC between the non-IDC and IDC groups (P=0.19), but MVV and MCC were significantly greater in the non-IDC group (P<0.001). There was no significant difference between MABC and MVV (MABC-MVV, P=0.54; MVV/MABC, P=0.07), but there was a significant difference between MABC and MCC between the non-IDC and IDC groups (MABC-MCC, P<0.001; MCC/MABC, P<0.001). Conclusions Maximum bladder capacity from a urodynamic study does not represent true bladder capacity because of involuntary contractions.

Background: A minimally invasive procedure for symptomatic pelvic bone metastasis is a feasible option for advanced cancer patients, and bone cement injection plays an essential role. Pulmonary embolism caused by thrombus, fat, or tumor emboli is a major complication related to bone cement injection, and increasing intraosseous pressure is a predisposing factor. This study aimed to quantify the degree of pressure change in the pelvic bone during percutaneous bone cement injection and investigate whether there is a significant decrease in intraosseous pressure when a decompressive route is additionally established. Methods: Bone cement injection into the acetabulum of swine pelvises by simulating the actual surgical procedure in terms of the injection method, bone cement, and surgical instruments was performed while recording the intraosseous pressure. Twenty swine pelvises were used and grouped into a decompression group and a non-decompression group. Bone cement injection and pressure measurement were conducted in the same way in both groups, but an additional decompressive route was established for each pelvis in the decompression group. Continuous variables were compared using the Mann-Whitney test. Results: The mean amount of injected bone cement was 19.8 mL and 20.3 mL and the mean speed of bone cement injection was 0.14 mL/sec and 0.12 mL/sec in the decompression group and the non-decompression group, respectively. The mean peak intraosseous pressures was 10.5 kPa with decompression and 37.8 kPa without decompression, and the difference was statistically significant (p < 0.01). Conclusions Intraosseous pressure during bone cement injection into swine pelvises was similar to that during vertebroplasty or kyphoplasty. When the additional decompression route was established, the intraosseous pressure decreased to one third the level.

Purpose: We aimed to identify risk factors for transurethral coagulation (TUC) using bipolar electrocautery for hemostasis during holmium laser enucleation of the prostate (HoLEP) surgery for benign prostatic hyperplasia (BPH). Methods: We analyzed the clinical outcomes of HoLEP surgery performed by a single surgeon between January 2010 and April 2020 at the Seoul National University Hospital. Patient characteristics and perioperative parameters were used to identify the risk factors for TUC. The TUC group was defined as a case of conversion to hemostasis using electrocautery during the hemostasis step after enucleation. Results: Of 1,563 patients, 357 underwent TUC (TUC group; 22.8%) as an adjuvant (n=299, 19.1%) or salvage (n=58, 3.7%) therapy. Patients in the TUC group were older (mean±standard deviation, 70.6±7.3 years vs. 69.3±7.0 years; P=0.002), had more 5-alpha reductase inhibitor (5-ARI) use (35.6% vs. 25.9%, P<0.001), higher serum prostate-specific antigen (PSA) (5.4 ±4.8 ng/mL vs. 3.8 ±4.5 ng/mL, P <0.001), larger total prostate volume (TPV) (89.5 ±44.7 mL vs. 66.0 ±32.6 mL, P<0.001), and larger transitional zone volume (TZV) (57.3±34.9 mL vs. 37.7±24.2 mL, P<0.001) than those who did not undergo TUC (non-TUC group). In univariate logistic regression analysis, age, 5-ARI use, PSA, TPV, and TZV correlated with TUC, whereas in multivariate logistic regression analysis, only TZV was associated with TUC. The odds ratios (ORs) of TUC were analyzed per TZV quartile. Compared to TZV<22.3 mL, the OR was 2.42 in 34.1 mL≤TZV<53.5 mL (95% confidence interval [CI], 1.58–3.72; P<0.001), 5.17 in ≥53.5 mL (95% CI, 3.44–7.77; P<0.001). Conclusions The risk of TUC during HoLEP surgery increases in patients with TZV >35 mL. Therefore, TUC may be potentially necessary in patients with a large transition zone volume in patients with BPH.

Background: Coronavirus disease 2019 (COVID-19) is generally asymptomatic or mild in otherwise healthy children, however, severe cases may occur. In this study, we report the clinical characteristics of children classified as critical COVID-19 in Korea to provide further insights into risk factors and management in children. Methods: This study was a retrospective case series of children < 18 years of age classified as critical COVID-19. Cases were identified by the Korea Disease Control and Prevention Agency surveillance system and medical records were reviewed. Critical COVID-19 was defined as cases with severe illness requiring noninvasive (high flow nasal cannula, continuous positive airway pressure, or bilevel positive airway pressure) or invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy (CRRT), between January 20, 2020 and October 7, 2021. Results: Among 39,146 cases diagnosed with COVID-19 in subjects < 18 years of age, eight cases (0.02%) were identified as critical COVID-19. The median age was 13 years (range 10 month–17 years) and male-to-female ratio was 1:1. Three children had underlying diseases; one child has asthma and major depressive disorder, one child had LennoxGastaut syndrome and one child had mental retardation and was newly diagnosed with type 2 diabetes mellitus with the diagnosis of COVID-19. Among the eight children, seven were obese (body mass index range [BMI] median 29.3, range 25.9–38.2, weight-for-length > 97% for infant) and one was overweight (BMI 21.3). All patients had fever, six patients had dyspnea or cough and other accompanied symptoms included sore throat, headache, lethargy and myalgia. Radiologic findings showed pneumonia within 1–8 days after symptom onset. Pneumonia progressed in these children for 2–6 days and was improved within 5–32 days after diagnosis. Among the eight critical cases, remdesivir was administered in six cases.Steroids were provided for all cases. Inotropics were administered in one case. Six cases were treated with noninvasive mechanical ventilator and three required mechanical ventilator. One case required ECMO due to acute respiratory distress syndrome. All cases were admitted to the intensive care unit and admission period ranged from 9–39 days. Among all critical COVID-19 cases < 18 years of age, there were no fatal cases. Conclusion To develop appropriate policies for children in the COVID-19 pandemic, it is important to monitor and assess the clinical burden in this population.

Background: Allogeneic hematopoietic stem cell transplantation (alloSCT) is a potentially curative treatment option for acute leukemia. We aimed to identify the comorbidity factors affecting survival outcomes after alloSCT and develop a new comorbidity index tool for predicting overall survival (OS). Methods: A Korean nationwide cohort of 3,809 adults with acute leukemia treated with alloSCT between January 2002 and December 2018 was analyzed as the development cohort.A retrospective cohort comprising 313 consecutive adults with acute leukemia who underwent alloSCT between January 2019 and April 2020 was analyzed as the validation cohort. Results: In the development cohort, advanced age, male sex, and comorbidities such as previous non-hematologic malignancy, hypertension, and coronary or cerebral vascular disease were significantly related to poor OS. Subsequently, a new comorbidity scoring system was developed, and risk groups were created, which included the low-risk (score ≤0.17), intermediate-risk (0.17＜ score ≤0.4), high-risk (0.4＜ score ≤0.55), and very high-risk (score ＞0.55) groups. The 1-year OS rates were discriminatively estimated at 73.5%, 66.2%, 61.9%, and 50.9% in the low-risk, intermediate-risk, high-risk, and very high-risk groups in the development cohort, respectively (P ＜0.001). The developed scoring system yielded discriminatively different 1-year OS rates and 1-year incidence of non-relapse mortality according to the risk group (P =0.085 and P =0.018, respectively).Furthermore, the developed model showed an acceptable performance for predicting 1-year non-relapse mortality with an area under the curve of 0.715. Conclusion The newly developed predictive scoring system could be a simple and reliable tool helping clinicians to assess risk of alloSCT in adults with acute leukemia.