Background: Hypercalcemia of malignancy (HCM), a major metabolic complication of cancer, is often managed with bisphosphonates (BP) and, increasingly, with denosumab. We aimed to compare the effectiveness and safety of denosumab with that of BP, with or without calcitonin, in treating HCM. Methods: This retrospective cohort study was conducted at a tertiary hospital from 2017 to 2022 and included 317 patients treated for HCM. Participants were divided into three treatment groups: denosumab, intravenous (IV) BP only, and IV BP combined with calcitonin. The primary outcomes measured were changes in calcium levels and the incidence of hypocalcemia. Analysis of covariance was used to adjust for age, sex, body mass index, creatinine level, type of malignancy, and the use of furosemide and steroids. Results: The mean participant age was 65 years, and 37.5% were female. After adjustment, both denosumab and IV BPs were found to effectively lower calcium levels. Denosumab led to a decrease of 2.0 mg/dL (−15.9%), while IV BP alone resulted in a reduction of 1.8 mg/dL (−13.9%). The largest reduction, of 2.7 mg/dL (−20.9%), occurred with IV BP and calcitonin. Both denosumab and IV BP+calcitonin yielded their lowest calcium levels within 48 hours, whereas the IV BP only group reached a nadir within 72 hours. Despite these differences in treatment effectiveness, hypocalcemia occurred significantly less frequently in the denosumab group compared to the other groups. Conclusion Denosumab and IV BP were similarly effective in reducing calcium levels. However, IV BP combined with calcitonin yielded a more rapid and pronounced decrease.

Background: The World Health Organization has declared the end of the coronavirus disease 2019 (COVID-19) public health emergency. However, this did not indicate the end of COVID-19. Several months after the infection, numerous patients complain of respiratory or nonspecific symptoms; this condition is called long COVID. Even patients with mild COVID-19 can experience long COVID, thus the burden of long COVID remains considerable. Therefore, we conducted this study to comprehensively analyze the effects of long COVID using multi-faceted assessments. Materials and Methods: We conducted a prospective cohort study involving patients diagnosed with COVID-19 between February 2020 and September 2021 in six tertiary hospitals in Korea. Patients were followed up at 1, 3, 6, 12, 18, and 24 months after discharge. Long COVID was defined as the persistence of three or more COVID-19-related symptoms. The primary outcome of this study was the prevalence of long COVID after the period of COVID-19. Results: During the study period, 290 patients were enrolled. Among them, 54.5 and 34.6% experienced long COVID within 6 months and after more than 18 months, respectively. Several patients showed abnormal results when tested for post-traumatic stress disorder (17.4%) and anxiety (31.9%) after 18 months. In patients who underwent follow-up chest computed tomography 18 months after COVID-19, abnormal findings remained at 51.9%. Males (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.53; P=0.004) and elderly (OR, 1.04; 95% CI, 1.00–1.09; P=0.04) showed a significant association with long COVID after 12–18 months in a multivariable logistic regression analysis. Conclusion Many patients still showed long COVID after 18 months post SARS-CoV-2 infection. When managing these patients, the assessment of multiple aspects is necessary.

Nerve growth factor (NGF) is a neurotrophic factor usually involved in the survival, differentiation, and growth of sensory neurons and nociceptive function. Yet, it has been suggested to play a role in the pathogenesis of osteoarthritis (OA). Previous studies suggested a possible relationship between NGF and OA; however, the underlying mechanisms remain unknown. Therefore, we investigated the impact of NGF in chondrogenesis using human induced pluripotent stem cells (hiPSCs)-derived chondrogenic pellets. To investigate how NGF affects the cartilage tissue, hiPSC-derived chondrogenic pellets were treated with NGF on day 3 of differentiation, expression of chondrogenic, hypertrophic, and fibrotic markers was confirmed. Also, inflammatory cytokine arrays were performed using the culture medium of the NGF treated chondrogenic pellets. As a result, NGF treatment decreased the expression of pro-chondrogenic markers by approximately 2∼4 times, and hypertrophic (pro-osteogenic) markers and fibrotic markers were increased by approximately 3-fold or more in the NGF-treated cartilaginous pellets. In addition, angiogenesis was upregulated by approximately 4-fold or more, bone formation by more than 2-fold, and matrix metalloproteinase induction by more than 2-fold. These inflammatory cytokine array were using the NGF-treated chondrogenic pellet cultured medium.Furthermore, it was confirmed by Western blot to be related to the induction of the glycogen synthase kinase-3 beta (GSK3β) pathway by NGF. In Conclusions, these findings provide valuable insights into the multifaceted role of NGF in cartilage hypertrophy and fibrosis, which might play a critical role in OA progression.

Background: Community acquired lower respiratory tract infection (LRTI) is a leading cause for hospitalization in children and important cause for antibiotic prescription. We aimed to describe the aetiology of LRTI in children and analyse factors associated with bacterial or viral infection. Methods: Patients aged < 19 years with a diagnosis of LRTI were identified from the Observational Medical Outcomes Partnership Common Data Model Database of Seoul National University Bundang Hospital from January 2005–July 2019, and their clinical characteristics were obtained from the electronic medical records and retrospectively reviewed. Results: Among 5,924 cases of LRTI, 74.2% were pneumonia and 25.8% were bronchiolitis/ bronchitis. Patients’ median age was 1.8 (interquartile range, 3.1) years and 79.9% were < 5 years old. Pathogens were identified in 37.8%; 69.1% were viral and 30.9% were bacterial/ Mycoplasma pneumoniae. Respiratory syncytial virus was most common (70.9%) among viruses and M. pneumoniae (94.6%) was most common among bacteria. Viral LRTI was associated with winter, age < 2 years, rhinorrhoea, dyspnoea, lymphocytosis, thrombocytosis, wheezing, stridor, chest retraction, and infiltration on imaging. Bacteria/ M. pneumoniae LRTI was associated with summer, age ≥ 2 years, fever, decreased breathing sounds, leucocytosis, neutrophilia, C-reactive protein elevation, and positive imaging findings (consolidation, opacity, haziness, or pleural effusion). Conclusion In children with LRTI, various factors associated with viral or bacterial/ M. pneumoniae infections were identified, which may serve as guidance for antibiotic prescription.

Background: Primary Merkel cell carcinoma of the salivary gland is currently not listed in the World Health Organization classification. However, cases of Merkel cell type neuroendocrine carcinomas of the salivary gland with perinuclear cytokeratin 20 positivity have been intermittently reported. We here investigated the clinicopathologic features of additional cases. Methods: Data of four cases of Merkel cell type small cell neuroendocrine carcinoma of the salivary gland were retrieved. To confirm the tumors’ primary nature, clinical records and pathologic materials were reviewed. Optimal immunohistochemical staining was performed to support the diagnosis. Results: All tumors were located in the parotid gland. Possibilities of metastasis were excluded in all cases through a meticulous clinicopathological review. Tumor histology was consistent with the diagnosis of small cell neuroendocrine carcinoma. Tumors’ immunohistochemical phenotypes were consistent with Merkel cell carcinoma, including Merkel cell polyomavirus large T antigen positivity in two of the four cases. Conclusions Merkel cell carcinomas can originate in salivary glands and are partly associated with Merkel cell polyomavirus infection as in cutaneous Merkel cell carcinomas.

Chronic active Epstein-Barr virus (CAEBV) can induce complications in various organs, including the brain and gastrointestinal tract. A 3-year-old boy was referred to the hospital with a history of fever and seizures for 15 days. A diagnosis of encephalitis based on computed tomography (CT) and magnetic resonance imaging findings and clinical correlation was made. Laboratory tests showed positive serology for Epstein-Barr virus (EBV) and negative for Rotavirus antigen and IgG and IgM antibodies for cytomegalovirus, herpes simplex virus, and varicella zoster virus, respectively. Abdominal CT showed diffuse wall thickening with fluid distension of small bowel loops, lower abdomen wall thickening, and a small amount of ascites. The biopsy demonstrated positive Epstein-Barr encoding region in situ hybridization in cells within the crypts and lamina propria. The patient was managed with steroids and hematopoietic stem cell transplantation (HSCT). This case showed histopathological characteristics of concurrent EBV-associated encephalitis and colitis in CAEBV infection. The three-step strategy of immunosuppressive therapy, chemotherapy, and allogeneic HSCT should be always be considered for prevention of disease progression.

The introduction of anti-amyloid therapies for Alzheimer’s disease (AD), such as lecanemab (Lequembi®), which was recently approved in Korea, necessitates careful monitoring for amyloid-related imaging abnormalities (ARIA) using brain MRI. To optimize ARIA monitoring in Korean clinical settings, the Korean Society of Neuroradiology (KSNR) and the Age and Neurodegeneration Imaging (ANDI) Study Group proposed MRI protocol recommendations on essential MR sequences, MRI acquisition parameters, timing and condition of MRI examinations, and essential details to provide a scientific basis for maximizing the safety and efficacy of AD treatment. A customized, standardized MRI protocol focusing on Korea’s healthcare environment can improve ARIA management and ensure patient safety through early detection of potential anti-amyloid therapy side effects, thereby enhancing treatment quality.

Background: Despite the increase in daily alcohol intake in recent decades and the implementation of national health screenings, effective management strategies for alcohol consumption remain outdated. This review evaluates intervention studies on screening and behavioral counseling for unhealthy alcohol use, with the aim of enhancing the effectiveness of interventions and improving health outcomes. Methods: On the basis of the GRADE (Grading of Recommendations Assessment, Development, and Evaluation)- ADOLOPMENT framework, systematic reviews and randomized controlled trials were examined to investigate the effectiveness of screening and counseling interventions in reducing unhealthy alcohol use. Five key questions were generated, and an evaluation and quality assessment of existing systematic reviews and new evidence related to each key question were conducted. Results: Updating the U.S. Preventive Services Task Force and Cochrane 2018 reviews, we identified five new randomized trials that evaluated screening and counseling interventions for unhealthy alcohol use. For Key Question 2, the sensitivity and specificity of the new screening studies were consistent with those of prior research. Brief interventions were confirmed to reduce alcohol use (Key Question 4a), although additional research is required for a wider array of health outcomes. One study highlighted the benefits of counseling interventions for newborn health indicators in pregnant women (Key Question 4b). No new evidence was found regarding the harms of screening (Key Question 3) or alcohol use reduction interventions (Key Question 5). Conclusion This review supports the continued use of brief interventions to reduce alcohol consumption in highrisk groups and highlights the need for culturally tailored research in Korea.

BACKGROUND/OBJECTIVES: Isoflavones are estrogen-like compounds found in plants and their health effects remain equivocal. We investigated dietary isoflavone intake and its associated factors in Korean breast cancer survivors, with a comparison to cancer-free women. SUBJECTS/METHODS: The usual dietary intake of breast cancer survivors (n = 981, mean age 52 yrs) in 9 hospitals between 2012 and 2019 was assessed using 3-day food records or food frequency questionnaires (FFQs). They were age-matched to 2,943 cancer-free women who completed FFQs as part of a nationwide study conducted between 2012 and 2016. We used the flavonoid database of common Korean foods and the Phenol-Explorer database to estimate isoflavone intake. The contribution of each food or food group to the total isoflavone intake was calculated. The adjusted least-squares means of dietary isoflavone intake according to lifestyle and clinical factors were calculated using generalized linear models. RESULTS: Breast cancer survivors had a higher mean dietary isoflavone intake (23.59 mg/day) than cancer-free women (17.81 mg/day). Major food sources, including tofu, soybeans, and doenjang, contributed to over 70% of the isoflavone intake in both groups. When we estimated dietary isoflavone intake according to lifestyle characteristics, isoflavone intake increased with higher scores of adherence to the American Cancer Society dietary guidelines but decreased with increasing body mass index in both groups. Among cancer-free women, dietary isoflavone intake was higher among those who had never smoked and among dietary supplement users. Among breast cancer survivors, dietary isoflavone intakes did not vary with clinical characteristics, including time since surgery and estrogen receptor status. CONCLUSION Breast cancer survivors were more likely to consume isoflavones than agematched cancer-free women. Dietary isoflavone intake was associated with healthy lifestyle characteristics in women both with and without breast cancer. Further research is needed to understand the role of the higher isoflavone intake among breast cancer survivors compared to cancer-free women on their prognosis.