Purpose: Notable effectiveness of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer (BC) has focused pathologists’ attention. We studied the incidence and clinicopathologic characteristics of HER2-low BC, and the effects of immunohistochemistry (IHC) associated factors on HER2 IHC results. Materials and Methods: The Breast Pathology Study Group of the Korean Society of Pathologists conducted a nationwide study using real-world data on HER2 status generated between January 2022 and December 2022. Information on HER2 IHC protocols at each participating institution was also collected. Results: Total 11,416 patients from 25 institutions included in this study. Of these patients, 40.7% (range, 6.0% to 76.3%) were classified as HER2-zero, 41.7% (range, 10.5% to 69.1%) as HER2-low, and 17.5% (range, 6.7% to 34.0%) as HER2-positive. HER2-low tumors were associated with positive estrogen receptor and progesterone receptor statuses (p < 0.001 and p < 0.001, respectively). Antigen retrieval times (≥ 36 minutes vs. < 36 minutes) and antibody incubation times (≥ 12 minutes vs. < 12 minutes) affected on the frequency of HER2 IHC 1+ BC at institutions using the PATHWAY HER2 (4B5) IHC assay and BenchMark XT or Ultra staining instruments. Furthermore, discordant results between core needle biopsy and subsequent resection specimen HER2 statuses were observed in 24.1% (787/3,259) of the patients. Conclusion The overall incidence of HER2-low BC in South Korea concurs with those reported in previously published studies. Significant inter-institutional differences in HER2 IHC protocols were observed, and it may have impact on HER2-low status. Thus, we recommend standardizing HER2 IHC conditions to ensure precise patient selection for targeted therapy.

Background: Alcohol consumption is a major risk factor for cancer, and when combined with smoking, the risk increases. Nevertheless, few studies have comprehensively evaluated the combined effects of alcohol consumption and smoking on the risk of various cancer types.Therefore, to assess these effects, we conducted a systematic review and meta-analysis. Methods: We performed a systematic search of five literature databases, focusing on cohort and case-control studies. Considering exposure levels, we quantified the combined effects of alcohol consumption and smoking on cancer risk and assessed multiplicative interaction effects. Results: Of 4,452 studies identified, 24 (4 cohort studies and 20 case-control studies) were included in the meta-analysis. We detected interaction effect of light alcohol and moderate smoking on head and neck cancer risk (relative risk [RR], 4.26; 95% confidence interval [CI], 2.50–7.26; I2 = 65%). A synergistic interaction was observed in heavy alcohol and heavy smoking group (RR, 35.24; 95% CI, 23.17–53.58; I2 = 69%). In more detailed cancer types, the interaction effect of heavy alcohol and heavy smoking was noticeable on oral (RR, 36.42; 95% CI, 24.62–53.87; I2 = 46%) and laryngeal (RR, 38.75; 95% CI, 19.25–78.01; I2 = 69%) cancer risk. Conclusion Our study provided a comprehensive summary of the combined effects of alcohol consumption and smoking on cancers. As their consumption increased, the synergy effect became more pronounced, and the synergy effect was evident especially for head and neck cancer. These findings provide additional evidence for the combined effect of alcohol and smoking in alcohol guidelines for cancer prevention.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused the death of thousands of patients worldwide. Although age is known to be a risk factor for morbidity and mortality in COVID-19 patients, critical illness or death is occurring even in the younger age group as the epidemic spreads. In early 2022, omicron became the dominant variant of the COVID-19 virus in South Korea, and the epidemic proceeded on a large scale. Accordingly, this study aimed to determine whether young adults (aged ≤ 50 years) with critical COVID-19 infection during the omicron period had different characteristics from older patients and to determine the risk factors for mortality in this specific age group. Methods: We evaluated 213 critical adult patients (high flow nasal cannula or higher respiratory support) hospitalized for polymerase chain reaction-confirmed COVID-19 in nine hospitals in South Korea between February 1, 2022 and April 30, 2022. Demographic characteristics, including body mass index (BMI) and vaccination status; underlying diseases; clinical features and laboratory findings; clinical course; treatment received; and outcomes were collected from electronic medical records (EMRs) and analyzed according to age and mortality. Results: Overall, 71 critically ill patients aged ≤ 50 years were enrolled, and 142 critically ill patients aged over 50 years were selected through 1:2 matching based on the date of diagnosis. The most frequent underlying diseases among those aged ≤ 50 years were diabetes and hypertension, and all 14 patients who died had either a BMI ≥ 25 kg/m 2 or an underlying disease. The total case fatality rate among severe patients (S-CFR) was 31.0%, and the S-CFR differed according to age and was higher than that during the delta period. The S-CFR was 19.7% for those aged ≤ 50 years, 36.6% for those aged > 50 years, and 38.1% for those aged ≥ 65 years. In multivariate analysis, age (odds ratio [OR], 1.084; 95% confidence interval [CI], 1.043–1.127), initial low-density lipoprotein > 600 IU/L (OR, 4.782; 95% CI, 1.584–14.434), initial C-reactive protein > 8 mg/dL (OR, 2.940; 95% CI, 1.042–8.293), highest aspartate aminotransferase > 200 IU/L (OR, 12.931; 95% CI, 1.691–98.908), and mechanical ventilation implementation (OR, 3.671; 95% CI, 1.294–10.420) were significant independent predictors of mortality in critical COVID-19 patients during the omicron wave. A similar pattern was shown when analyzing the data by age group, but most had no statistical significance owing to the small number of deaths in the young critical group. Although the vaccination completion rate of all the patients (31.0%) was higher than that in the delta wave period (13.6%), it was still lower than that of the general population. Further, only 15 (21.1%) critically ill patients aged ≤ 50 years were fully vaccinated. Overall, the severity of hospitalized critical patients was significantly higher than that in the delta period, indicating that it was difficult to find common risk factors in the two periods only with a simple comparison. Conclusion Overall, the S-CFR of critically ill COVID-19 patients in the omicron period was higher than that in the delta period, especially in those aged ≤ 50 years. All of the patients who died had an underlying disease or obesity. In the same population, the vaccination rate was very low compared to that in the delta wave, indicating that non-vaccination significantly affected the progression to critical illness. Notably, there was a lack of prescription for Paxlovid for these patients although they satisfied the prescription criteria. Early diagnosis and active initial treatment was necessary, along with the proven methods of vaccination and personal hygiene. Further studies are needed to determine how each variant affects critically ill patients.

OBJECTIVES: Alcohol consumption is a well-established risk factor for cancer. Despite extensive research into the relationship between alcohol consumption and cancer risk, the effect of light alcohol consumption on cancer risk remains a topic of debate. To contribute to this discourse, we conducted a comprehensive systematic review and meta-analysis. METHODS: Our systematic review aimed to investigate the associations between different levels of alcohol consumption and the risk of several cancer types. We focused on analyzing prospective associations using data from 139 cohort studies. Among them, 106 studies were included in the meta-analysis after a quantitative synthesis. RESULTS: Our analysis did not find a significant association between light alcohol consumption and all-cause cancer risk (relative risk, 1.02; 95% confidence interval, 0.99 to 1.04), but we observed a dose-response relationship. Light alcohol consumption was significantly associated with higher risks of esophageal, colorectal, and breast cancers. Light to moderate drinking was associated with elevated risks of esophageal, colorectal, laryngeal, and breast cancers. Heavy drinking was also found to contribute to the risk of stomach, liver, pancreas, and prostate cancers, thereby increasing the risk of almost all types of cancer. Additionally, females generally had lower cancer risks compared to males. CONCLUSIONS Our findings highlight that cancer risks extend beyond heavy alcohol consumption to include light alcohol consumption as well. These findings suggest that there is no safe level of alcohol consumption associated with cancer risk. Our results underscore the importance of public health interventions addressing alcohol consumption to mitigate cancer risks.

Purpose: This study aimed to evaluate the effect of waiting time, from diagnosis to initiation of definitive concurrent chemoradiation (CCRT), on overall survival in cervical cancer patients. Materials and Methods: Patients with cervical cancer who were treated with definitive CCRT between 2000 and 2017 were retrospectively reviewed. Time from initial pathological diagnosis to definitive CCRT was analyzed both as a continuous variable (per day) and as a categorical variable in two groups (group 1 ≤ median, group 2 > median). Patients with a waiting time of more than 60 days were excluded. Results: The median waiting time was 14 days (0-60). There were differences between group 1 and group 2 in age and chemotherapy regimens. However, no significant difference was found in the International Federation of Gynecology and Obstetrics stage, cell type, or the number of cycles of chemotherapy received during CCRT. A longer waiting time was associated with poorer overall survival on the Kaplan-Meier curve (group 1 vs. group 2, p=0.042). On multivariate analysis, intervals as either a continuous variable (hazard ratio [HR], 1.023; 95% confidence interval [CI], 1.006 to 1.040; p=0.007) or a categorical variable (HR, 1.513; 95% CI, 1.073 to 2.134; p=0.018), FIGO stage, cell type, and the number of cycles of chemotherapy received during CCRT were significant independent prognostic factors for overall survival. Conclusion A shorter waiting time from pathological diagnosis to definitive CCRT showed benefit on overall survival. Our findings suggest that an effort to minimize waiting times should be recommended in cervical cancer patients who are candidates for CCRT.

Background: Numerous patients around the globe are dying from coronavirus disease 2019 (COVID-19). While age is a known risk factor, risk analysis in the young generation is lacking. The present study aimed to evaluate the clinical features and mortality risk factors in younger patients (≤ 50 years) with a critical case of COVID-19 in comparison with those among older patients (> 50 years) in Korea. Methods: We analyzed the data of adult patients only in critical condition (requiring high flow nasal cannula oxygen therapy or higher respiratory support) hospitalized with PCR-confirmed COVID-19 at 11 hospitals in Korea from July 1, 2021 to November 30, 2021 when the delta variant was a dominant strain. Patients’ electronic medical records were reviewed to identify clinical characteristics. Results: During the study period, 448 patients were enrolled. One hundred and forty-two were aged 50 years or younger (the younger group), while 306 were above 50 years of age (the older group). The most common pre-existing conditions in the younger group were diabetes mellitus and hypertension, and 69.7% of the patients had a body mass index (BMI) > 25 kg/m 2 .Of 142 younger patients, 31 of 142 patients (21.8%, 19 women) did not have these pre-existing conditions. The overall case fatality rate among severity cases was 21.0%, and it differed according to age: 5.6% (n = 8/142) in the younger group, 28.1% in the older group, and 38% in the ≥ 65 years group. Age (odds ratio [OR], 7.902; 95% confidence interval [CI], 2.754–18.181), mechanical ventilation therapy (OR, 17.233; 95% CI, 8.439–35.192), highest creatinine > 1.5 mg/dL (OR, 17.631; 95% CI, 8.321–37.357), and combined blood stream infection (OR, 7.092;95% CI, 1.061–18.181) were identified as independent predictors of mortality in total patients.Similar patterns were observed in age-specific analyses, but most results were statistically insignificant in multivariate analysis due to the low number of deaths in the younger group.The full vaccination rate was very low among study population (13.6%), and only three patients were fully vaccinated, with none of the patients who died having been fully vaccinated in the younger group. Seven of eight patients who died had a pre-existing condition or were obese (BMI > 25 kg/m 2 ), and the one remaining patient died from a secondary infection. Conclusion About 22% of the patients in the young critical group did not have an underlying disease or obesity, but the rate of obesity (BMI > 25 kg/m2 ) was high, with a fatality rate of 5.6%. The full vaccination rate was extremely low compared to the general population of the same age group, showing that non-vaccination has a grave impact on the progression of COVID-19 to a critical condition. The findings of this study highlight the need for measures to prevent critical progression of COVID-19, such as vaccinations and targeting young adults especially having risk factors.

Background: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated. Methods: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model. Results: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids (P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03–13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26–14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P= 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089). Conclusion Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients.

The current multimorbidity correction method in the Global Burden of Disease studies assumes the independent occurrence of diseases. Those studies use Monte-Carlo simulations to adjust for the presence of multiple disease conditions for all diseases. The present study investigated whether the above-mentioned assumption is reasonable based on the prevalence confirmed from actual data. This study compared multimorbidity-adjusted years of lived with disability (YLD) obtained by Monte-Carlo simulations and multimorbidity-adjusted YLD using multimorbidity prevalence derived from National Health Insurance Service data. The 5 most common diseases by sex and age groups were selected as diseases of interest. No significant differences were found between YLD estimations made using actual data and Monte-Carlo simulations, even though assumptions about the independent occurrence of diseases should be carefully applied. The prevalence was not well reflected according to disease characteristics in those under the age of 30, among whom there was a difference in YLD between the 2 methods. Therefore, when calculating the burden of diseases for Koreans over the age of 30, it is possible to calculate the YLD with correction for multimorbidity through Monte-Carlo simulation, but care should be taken with under-30s. It is useful to apply the efficiency and suitability of calibration for multiplicative methods using Monte-Carlo simulations in research on the domestic disease burden, especially in adults in their 30s and older. Further research should be carried out on multimorbidity correction methodology according to the characteristics of multiple diseases by sex and age.

Purpose: A total of 39 seafood menus were prepared according to the Korean standard recipe, and analyzed for vitamin B 9 (folate) and B 12 (cobalamins) contents, using validated applied analytical methods. The menus included Guk/Tang/Jjigae (boiled or stewed dishes, n = 10), Bokkeum (stir-fried dishes, n = 10), Jjim/Jorim (braised or steamed dishes, n = 7), Gui (baked or grilled dishes, n = 7), Twigim (deep-fried dishes, n = 2) and Muchim (dried or blanchedseasoned dishes, n = 3). Methods: The contents of vitamin B 9 and B12 in all food samples were determined by the trienzyme extraction-Lactobacillus casei and immunoaffinity-high-performance liquid chromatography/photodiode array detection methods. Analytical quality control was performed in order to assure reliability of the analysis. Results: Accuracy (97.4–100.6% recoveries) and precision (< 6% relative standard deviations for repeatability and reproducibility) of vitamin B 9 and B12 analyses were determined to be excellent. The vitamin B 9 and B 12 contents of the 39 seafood menus evaluated, varied in the range of 1.83–523.08 μg/100 g and 0.11–38.30 μg/100 g, respectively, depending on the ingredients and cooking methods. The vitamin B 9 content was highest in Jomi-gim (523.08 μg/100 g), followed by Geonsaeu-bokkeum (128.34 μg/100 g) and Janmyeolchi-bokkeum (121.53 μg/100 g). Vitamin B12 was detected in all seafood menus, with highest level obtained in Kkomack-jjim (41.58 μg/100 g). The seaweed dish was found to have high levels of both vitamin B 9 and B12 . All assays were performed under strict quality control. Conclusion Guk and Tang menus, which contain a large amount of water, were relatively lower in the vitamin B 9 and B12 contents than the other menus. Bokkeum menus containing various vegetables were high in the vitamin B 9 content, but the vitamin B12 content was dependent on the type of seafood used in the menu.

Natural killer (NK) cell enteropathy is not well understood. Although NK-cell enteropathy is typically benign, aggressive NK-cell lymphoma is an important differential diagnosis. This paper reports a rare case of NK-cell enteropathy of the stomach presenting with dyspepsia and weight loss. In this case, upper endoscopy revealed an ulcer-like lesion (approximately 7 mm) surrounded by erythema, edema, and mucosal hemorrhage. The biopsy revealed atypical lymphocyte cells expressing CD56 without an Epstein-Barr virus infection, which is consistent with NK-cell enteropathy. Follow-up endoscopy 2 months later revealed lesion regression with mild erythema. The patient was observed closely for 6 months, with no evidence of lymphoma.