Background: Although patients with lymphoma appear particularly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the clinical evolution of coronavirus disease 2019 (COVID-19) in a patient with lymphoid malignancies has been under-represented, especially in relation to chemo-, chemo-immunotherapy. Materials and Methods: Among adult patients with lymphoma receiving treatment in a specialized lymphoma center at a 500-bed, university-affiliated hospital, we retrospectively reviewed the medical records of patients diagnosed with SARS-CoV-2 infection from January 2020 to April 2022. Results: A total of 117 patients with a median age of 53 years were included. One hundred twelves (95.7%) were non-Hodgkin lymphoma. Eighty-six patients (73.5%) were on active chemotherapy and 9 were post stem cell transplant state. Sixty-one patients had more than one comorbidity and 29 had hypogammaglobulinemia. Thirty-four patients (29.1%) had never received a COVID-19 vaccine. During a median follow-up of 134 days, COVID-19 pneumonia developed in 37 patients (31.6%). Excluding three patients who died before the 30 days, 31 out of 34 patients had ongoing symptomatic COVID-19. Eleven patients (9.4%) had post COVID-19 lung condition that persisted 90 days after COVID-19 diagnosis. Overall mortality was 10.3% (12 of 117), which was higher in patients with pneumonia. In multivariate analyses, age 65 years or older, follicular lymphoma, receiving rituximab maintenance therapy, and lack of vaccination were significantly associated with the development of COVID-19 pneumonia. Conclusion Patients with lymphoma are at high risk for developing pneumonia after SARS-CoV-2 infection and suffer from prolonged symptoms. More aggressive vaccination and protective measures for patients with lymphoma who have impaired humoral response related to rituximab maintenance therapy and hypogammaglobulinemia are needed.

Background: Although patients with lymphoma appear particularly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the clinical evolution of coronavirus disease 2019 (COVID-19) in a patient with lymphoid malignancies has been under-represented, especially in relation to chemo-, chemo-immunotherapy. Materials and Methods: Among adult patients with lymphoma receiving treatment in a specialized lymphoma center at a 500-bed, university-affiliated hospital, we retrospectively reviewed the medical records of patients diagnosed with SARS-CoV-2 infection from January 2020 to April 2022. Results: A total of 117 patients with a median age of 53 years were included. One hundred twelves (95.7%) were non-Hodgkin lymphoma. Eighty-six patients (73.5%) were on active chemotherapy and 9 were post stem cell transplant state. Sixty-one patients had more than one comorbidity and 29 had hypogammaglobulinemia. Thirty-four patients (29.1%) had never received a COVID-19 vaccine. During a median follow-up of 134 days, COVID-19 pneumonia developed in 37 patients (31.6%). Excluding three patients who died before the 30 days, 31 out of 34 patients had ongoing symptomatic COVID-19. Eleven patients (9.4%) had post COVID-19 lung condition that persisted 90 days after COVID-19 diagnosis. Overall mortality was 10.3% (12 of 117), which was higher in patients with pneumonia. In multivariate analyses, age 65 years or older, follicular lymphoma, receiving rituximab maintenance therapy, and lack of vaccination were significantly associated with the development of COVID-19 pneumonia. Conclusion Patients with lymphoma are at high risk for developing pneumonia after SARS-CoV-2 infection and suffer from prolonged symptoms. More aggressive vaccination and protective measures for patients with lymphoma who have impaired humoral response related to rituximab maintenance therapy and hypogammaglobulinemia are needed.

Background: Although patients with lymphoma appear particularly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the clinical evolution of coronavirus disease 2019 (COVID-19) in a patient with lymphoid malignancies has been under-represented, especially in relation to chemo-, chemo-immunotherapy. Materials and Methods: Among adult patients with lymphoma receiving treatment in a specialized lymphoma center at a 500-bed, university-affiliated hospital, we retrospectively reviewed the medical records of patients diagnosed with SARS-CoV-2 infection from January 2020 to April 2022. Results: A total of 117 patients with a median age of 53 years were included. One hundred twelves (95.7%) were non-Hodgkin lymphoma. Eighty-six patients (73.5%) were on active chemotherapy and 9 were post stem cell transplant state. Sixty-one patients had more than one comorbidity and 29 had hypogammaglobulinemia. Thirty-four patients (29.1%) had never received a COVID-19 vaccine. During a median follow-up of 134 days, COVID-19 pneumonia developed in 37 patients (31.6%). Excluding three patients who died before the 30 days, 31 out of 34 patients had ongoing symptomatic COVID-19. Eleven patients (9.4%) had post COVID-19 lung condition that persisted 90 days after COVID-19 diagnosis. Overall mortality was 10.3% (12 of 117), which was higher in patients with pneumonia. In multivariate analyses, age 65 years or older, follicular lymphoma, receiving rituximab maintenance therapy, and lack of vaccination were significantly associated with the development of COVID-19 pneumonia. Conclusion Patients with lymphoma are at high risk for developing pneumonia after SARS-CoV-2 infection and suffer from prolonged symptoms. More aggressive vaccination and protective measures for patients with lymphoma who have impaired humoral response related to rituximab maintenance therapy and hypogammaglobulinemia are needed.

Background: The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) approved empagliflozin for reducing cardiovascular mortality and heart failure (HF) hospitalization in patients with both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). However, limited data are available on the generalizability of empagliflozin to clinical practice. Therefore, we evaluated real-world eligibility and potential cost-effectiveness based on a nationwide prospective HF registry. Methods: A total of 3,108 HFrEF and 2,070 HFpEF patients from the Korean Acute Heart Failure (KorAHF) registry were analyzed. Eligibility was estimated by inclusion and exclusion criteria of EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) and EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Preserved Ejection Fraction (EMPEROR-Preserved) trials and by FDA & EMA label criteria. The cost-utility analysis was done using a Markov model to project the lifetime medical cost and quality-adjusted life year (QALY). Results: Among the KorAHF patients, 91.4% met FDA & EMA label criteria, while 44.7% met the clinical trial criteria. The incremental cost-effectiveness ratio of empagliflozin was calculated at US$6,764 per QALY in the overall population, which is far below a threshold of US$18,182 per QALY. The cost-effectiveness benefit was more evident in patients with HFrEF (US$5,012 per QALY) than HFpEF (US$8,971 per QALY). Conclusion There is a large discrepancy in real-world eligibility for empagliflozin between FDA & EMA labels and clinical trial criteria. Empagliflozin is cost-effective in HF patients regardless of ejection fraction in South Korea health care setting. The efficacy and safety of empagliflozin in real-world HF patients should be further investigated for a broader range of clinical applications.

Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

BACKGROUND/OBJECTIVES: Premenstrual syndrome (PMS) is a disorder characterized by repeated emotional, behavioral, and physical symptoms before menstruation, and the exact cause and mechanism are uncertain. Hyperprolactinemia interferes with the normal production of estrogen and progesterone, leading to PMS symptoms. Thus, we judged that the inhibition of prolactin hypersecretion could mitigate PMS symptoms.MATERIALS/METHODS: Hordeum vulgare L. extract (HVE), Chrysanthemum zawadskii var. latilobum extract (CZE), and Lomens-P0 the mixture of these extracts were tested in subsequent experiments. The effect of extracts on prolactin secretion at the in vitro level was measured in GH3 cells. Nitric oxide and pro-inflammatory mediator expression were measured in RAW 264.7 cells to confirm the anti-inflammatory effect. Also, the hyperprolactinemic Institute for Cancer Research (ICR) mice model was used to measure extract effects on prolactin and hormone secretion and uterine inflammation. RESULTS: Anti-inflammatory effects of and prolactin secretion suppress by HVE and CZE were confirmed through in vitro experiments (P < 0.05). Treatment with Lomens-P0 inhibited prolactin secretion (P < 0.05) and restored normal sex hormone secretion in the hyperprolactinemia mice model. In addition, extracts significantly inhibited the expression of pro-inflammatory biomarkers, including interleukin-1β, and -6, tumor necrosis factor-α, inducible nitric oxide synthase, and cyclooxygenase-2 (P < 0.01). We used high-performance liquid chromatography analyses to identify tricin and chlorogenic acid as the respective components of HVE and CZE that inhibit prolactin secretion. The Lomens-P0, which includes tricin and chlorogenic acid, is expected to be effective in improving PMS symptoms in the human body. CONCLUSIONS The Lomens-P0 suppressed the prolactin secretion in hyperprolactinemia mice, normalized the sex hormone imbalance, and significantly suppressed the expression of inflammatory markers in uterine tissue. This study suggests that Lomens-P0 may have the potential to prevent or remedy materials to PMS symptoms.

The KOrean College of Rheumatology BIOlogics and targeted therapy (KOBIO) registry is a nationwide observational cohort that captures detailed data on exposure of patients to biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARDs). This registry was launched in December 2012 with an aim to prospectively investigate clinical manifestations and outcomes of patients with rheumatoid arthritis (RA), ankylosing spondylitis, and psoriatic arthritis who initiated a biologic or targeted synthetic DMARD or switched to another. Demographic data, disease activity, current treatment, adverse events, terms based on Medical Dictionary for Regulatory Activities, and so on are registered for patients who are then followed up annually in a web-based unified platform. The KOBIO registry also recruits and collects data of patients with RA on conventional DMARDs for comparison. As of today, more than 5,500 patients were enrolled from 47 academic and community Rheumatology centers across Korea. The KOBIO registry has evolved to become a powerful database for clinical research to improve clinical outcomes and quality of treatment.

Background/Aims: Effect of proton pump inhibitor (PPI) use on the risk of hipfracture is controversial. This study aimed to clarify the association between PPIuse and hip fracture risk using a large cohort. Methods: This study recruited participants from the nationwide cohort (n =1,025,340). After exclusion of participants who had hip fractures or were aged less than 40 years during the baseline period (2002 to 2004), 371,806 participants were followed to 2013. Participants prescribed PPIs for more than 90 days during baseline period were defined as users. Fracture cases were defined when participants were hospitalized with claims of a hip fracture. Results During 4,159,343 person-years of follow-up, fractures developed more oftenin PPI users than in nonusers (relative risk [RR], 1.787; 95% confidence interval [CI], 1.260 to 2.534; p = 0.002). The results persisted after adjusting for age, sex, andmany drugs relevant to osteoporosis or influential in bone health. Furthermore,fracture risk associated with PPI use increased with duration of use ( p trend < 0.001). The fully adjusted RRs of hip fracture development were 1.350 (95% CI, 1.203 to 1.515) for 1- to 90-day users, 1.487 (95% CI, 0.957 to 2.311) for 91- to 180-day users, and 1.771 (95% CI, 0.931 to 3.368) for > 180-day users. The positive association between PPI use and fracture was also confirmed in a subgroup with health screening data where further adjustment for body mass index, smoking status, alcohol consumption, and physical activity was available (adjusted RR, 2.025; 95% CI, 1.151 to 3.564, p = 0.014). Conclusions: PPI use is associated with hip fracture development.

Background: There are sparse data on the utilization rate of implantable cardioverterdefibrillator (ICD) and its beneficial effects in Korean patients with heart failure with reduced left ventricular ejection fraction (LVEF). Methods: Among 5,625 acute heart failure (AHF) patients from 10 tertiary university hospitals across Korea, 485 patients with reassessed LVEF ≤ 35% at least 3 months after the index admission were enrolled in this study. The ICD implantation during the follow-up was evaluated. Mortality was compared between patients with ICDs and age-, sex-, and follow-up duration matched control patients. Results: Among 485 patients potentially indicated for an ICD for primary prevention, only 56 patients (11.5%) underwent ICD implantation during the follow-up. Patients with ICD showed a significantly lower all-cause mortality compared with their matched control population: adjusted hazard ratio (HR) (95% confidence interval [CI]) = 0.39 (0.16–0.92), P = 0.032. The mortality rate was still lower in the ICD group after excluding patients with cardiac resynchronization therapy (adjusted HR [95% CI] = 0.09 [0.01–0.63], P = 0.015).According to the subgroup analysis for ischemic heart failure, there was a significantly lower all-cause mortality in the ICD group than in the no-ICD group (HR [95% CI] = 0.20 [0.06– 0.72], P = 0.013), with a borderline statistical significance (interaction P = 0.069). Conclusion Follow-up data of this large, multicenter registry suggests a significant underutilization of ICD in Korean heart failure patients with reduced LVEF. Survival analysis implies that previously proven survival benefit of ICD in clinical trials could be extrapolated to Korean patients.