Background: This retrospective observational matched-cohort study of 2,151,216 individuals from the Korean coronavirus disease 2019 (COVID-19) vaccine effectiveness cohort aimed to evaluate the comparative effectiveness of the COVID-19 bivalent versus monovalent vaccines in providing additional protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, critical infection, and death in Korea. Methods: Among individuals, those vaccinated with COVID-19 bivalent vaccines were matched in a 1:1 ratio with those who were vaccinated with monovalent vaccines (bivalent vaccines non-recipients) during the observation period. We fitted a time-dependent Cox proportional-hazards model to estimate hazard ratios (HRs) of COVID-19 outcomes for infection, critical infection, and death, and we defined vaccine effectiveness (VE) as 1–HR. Results: Compared with the bivalent vaccination group, the incidence proportions in the monovalent vaccination group were approximately three times higher for infection, nine times higher for critical infection, and 11 times higher for death. In the early stage of bivalent vaccination, relative VE of bivalent vaccine against monovalent vaccine was 42.4% against SARS-CoV-2 infection, 81.3% against critical infection, and 85.3% against death. In addition, VE against critical infection and death according to the elapsed period after bivalent vaccination was maintained at > 70%. Conclusion The bivalent booster dose provided additional protection against SARS-CoV-2 infections, critical infections, and deaths during the omicron variant phase of the COVID-19 pandemic.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis. Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Purpose: There are increased therapeutic usages of rituximab in kidney transplantation (KT). However, few studies have evaluated the effect of rituximab on cancer development following KT. This study aimed to evaluate the effect of rituximab on the cancer occurrence and mortality rate according to each type of cancer. Methods: Five thousand consecutive recipients who underwent KT at our center were divided into era1 (1990–2007) and era2-rit– (2008–2018), and era2-rit+ (2008–2018) groups. The era2-rit+ group included patients who received single-dose rituximab (200–500 mg) as a desensitization treatment 1–2 weeks before KT. Results: The 5-year incidence rates of malignant tumors after KT were 3.1%, 4.3%, and 3.5% in the era1, era2-rit–, and era2-rit+ group, respectively. The overall incidence rate of cancer after transplantation among the 3 study groups showed no significant difference (P = 0.340). The overall cancer-related mortality rate was 17.1% (53 of 310). Hepatocellular carcinoma (HCC) had the highest mortality rate (61.5%) and relative risk of cancer-related death (hazard ratio, 8.29; 95% confidence interval, 2.40–28.69; P = 0.001). However, we found no significant association between rituximab and the incidence of any malignancy. Conclusion Our results suggest that single-dose rituximab for desensitization may not increase the risk of malignant disease or cancer-related mortality in KT recipients. HCC was associated with the highest risk of cancer-related mortality in an endemic area of HBV infection.

End-stage renal disease (ESRD) patients on hemodialysis have poor nutritional status and associated problems such as inflammation and sarcopenia. Blood urea nitrogen (BUN) is an important measure of uremic toxins, and urea reduction is a marker of hemodialysis efficacy. However, a low protein diet for lower BUN could aggravate malnutrition in patients, and optimal pre-dialysis BUN is not defined. We investigated the association of pre-dialysis BUN with patients’ comorbidities and the relationship between pre-dialysis BUN and serum albumin as a nutrient marker. Among the 67 patients, the average pre- and post-dialysis BUN were 59.2 and 15.0 mg/dL, respectively, serum creatinine was 10.1 mg/dL, and the average serum albumin was 4.0 g/dL. Patients’ age was negatively correlated with serum creatinine (r=−0.277, p<0.05) and albumin (r=−0.453, p<0.001). Predialysis BUN showed a significant positive correlation with serum albumin (r=0.287, p<0.05) and creatinine (r=0.454, p<0.001). However, the predialysis BUN was not significantly related to diabetes, coronary artery disease, congestive heart failure, or cerebrovascular disease. Hemodialysis patients with high pre-dialysis BUN and high serum creatinine could be regarded as having good nutritional status. The significance of this study lies in the potential utility of pre-dialysis blood urea nitrogen as an indicator of the nutritional status of patients. Liberal protein intake might be recommended to adequately dialyzed patients.

Background: White matter hyperintensity (WMH) is a risk factor for dementia and ischemic stroke. The atherogenic index of plasma (AIP) is a simple and cost-effective marker for the prediction of various vascular diseases. In this study, we evaluated the relationship between AIP and WMH in adults without cerebrovascular accidents. Methods: We analyzed the data of 281 adults, aged ≥26 years, who underwent brain magnetic resonance imaging (MRI) at the health promotion center of an education hospital between January 2014 and December 2018. Participants were divided into three categories according to tertiles of the AIP scores (T1: <0.20; T2: 0.20–0.48; and T3: >0.48). WMH was defined as a modified Fazekas scale score of 1–3 on brain MRI. A cubic spline curve was used to determine the linearity of the relationship between AIP and WMH. Multiple logistic regression analysis was used to evaluate the relationship between the AIP and WMH. Results: The prevalence of WMH was 45.7% in T1, 57.0% in T2, and 66.0% in T3 (T3 vs. T1, P for post-hoc analysis=0.005). The increased odds of WMH were associated with increased AIP. The odds ratio (OR) with a 95% confidence interval (CI) for WMH of T2 and T3 compared with T1 were 1.57 (0.88–2.80) and 2.30 (1.28–4.14), respectively. After adjusting for confounding variables, the OR with a 95% CI for WMH in the T2 and T3 groups vs. the referent T1 were 1.55 (0.76–3.13) and 2.27 (1.06–4.84), respectively. Conclusion AIP is independently and positively associated with WMH in a healthy population.

Hyperparathyroidism is common in patients with chronic kidney disease with reduced renal function and has been observed after kidney transplantation. The optimal treatment for cases in which hyperparathyroidism persists after kidney transplantation has not been determined. Methods: This retrospective study included 83 patients with tertiary hyperparathyroidism who underwent kidney transplantation between 2000 and 2018 at a single tertiary center in Korea. Sixty-four patients underwent parathyroidectomy and 19 patients were treated with cinacalcet following renal transplantation. Biochemical parameters and clinical outcomes were compared between the two groups. Results: Serum calcium and parathyroid hormone (PTH) levels improved in both the parathyroidectomy and cinacalcet groups. One year after treatment, parathyroidectomy resulted in a lower mean serum calcium level than cinacalcet (9.7 ± 0.7 mg/dL vs. 10.5 ± 0.7 mg/dL, p = 0.001). Regarding serum PTH, the parathyroidectomy group showed a significantly lower PTH level than the cinacalcet group at 6 months (129.1 ± 80.3 pg/mL vs. 219.2 ± 92.5 pg/mL, p = 0.002) and 1 year (118.8 ± 75.5 pg/mL vs. 250.6 ± 94.5 pg/ mL, p < 0.001). There was no statistically significant difference in the incidence of kidney transplant rejection, graft failure, cardiovascular events, fracture risk, or bone mineral density changes between the two groups. Conclusion: Parathyroidectomy appears to reduce PTH and calcium levels effectively in tertiary hyperparathyroidism. However, creatinine level and allograft rejection should be monitored closely.

Background: We investigated the incidence and risk of retinal vein occlusion (RVO) in endstage renal disease (ESRD) patients on dialysis in Korea. Methods: In this nationwide cohort study, we used Korean National Health Insurance Service data between 2004 and 2013 for analysis. ESRD patients who started dialysis from 2004 to 2013 and an equal number of controls were selected through propensity score matching. RVO incidence in both cohorts were calculated for 2004–2013 using washout data from 2003. The multivariable Cox proportional hazards model was used to assess the risk of RVO in dialysis cohort. The Kaplan-Meier method was used to generate the cumulative RVO incidence curve.Whether the dialysis modality affects the development of RVO was also evaluated. Results: In this study, 74,551 ESRD patients on dialysis and the same number of controls were included. The incidence of RVO was significantly higher in the dialysis cohort than in the control cohort (dialysis = 7.3/1,000 person-years [PY]; control = 1.9/1,000 PY; P < 0.001). The cumulative-incidence of RVO was also significantly higher in the dialysis cohort than in the control cohort (P < 0.001; log-rank test). However, there was no significant difference in the incidence of RVO between the two dialysis methods (P = 0.550; log-rank test). Conclusion This study provided epidemiological evidence that receiving dialysis for ESRD could increase the risk of developing RVO. We also found a rapid increase in the incidence of RVO with a longer dialysis period. These results strengthen the relationship between retinal vascular disease and renal function.

Gastroesophageal reflux disease (GERD) is a condition in which gastric contents regurgitate into the esophagus or beyond, resulting in either troublesome symptoms or complications. GERD is heterogeneous in terms of varied manifestations, test findings, and treatment responsiveness. GERD diagnosis can be established with symptomatology, pathology, or physiology. Recently the Lyon consensus defined the “proven GERD” with concrete evidence for reflux, including advanced grade erosive esophagitis (Los Angeles classification grades C and or D esophagitis), long-segment Barrett’s mucosa or peptic strictures on endoscopy or distal esophageal acid exposure time > 6% on 24-hour ambulatory pH-impedance monitoring. However, some Asian researchers have different opinions on whether the same standards should be applied to the Asian population. The prevalence of GERD is increasing in Asia. The present evidence-based guidelines were developed using a systematic review and meta-analysis approach. In GERD with typical symptoms, a proton pump inhibitor test can be recommended as a sensitive, cost-effective, and practical test for GERD diagnosis.Based on a meta-analysis of 19 estimated acid-exposure time values in Asians, the reference range upper limit for esophageal acid exposure time was 3.2% (95% confidence interval, 2.7-3.9%) in the Asian countries. Esophageal manometry and novel impedance measurements, including mucosal impedance and a post-reflux swallow-induced peristaltic wave, are promising in discrimination of GERD among different reflux phenotypes, thus increasing its diagnostic yield. We also propose a long-term strategy of evidence-based GERD treatment with proton pump inhibitors and other drugs.

Background: Inflammatory bowel disease (IBD), including both Crohn’s disease and ulcerative colitis, are chronic human diseases that are challenging to cure and are often unable to be resolved. The inbred mouse strain C57BL/ 6 N has been used in investigations of IBD as an experimental animal model. The purpose of the current study was to compare the inflammatory responsiveness of C57BL/6NKorl mice, a sub-strain recently established by the National Institute of Food and Drug Safety Evaluation (NIFDS), with those of C57BL/6 N mice from two different sources using a dextran sulfate sodium (DSS)-induced colitis model. Results: Male mice (8 weeks old) were administered DSS (0, 1, 2, or 3%) in drinking water for 7 days. DSS significantly decreased body weight and colon length and increased the colon weight-to-length ratio. Moreover, severe colitisrelated clinical signs including diarrhea and rectal bleeding were observed beginning on day 4 in mice administered DSS at a concentration of 3%. DSS led to edema, epithelial layer disruption, inflammatory cell infiltration, and cytokine induction (tumor necrosis factor-α, interleukin-6, and interleukin-1β) in the colon tissues. However, no significant differences in DSS-promoted abnormal symptoms or their severity were found between the three sub-strains. Conclusions These results indicate that C57BL/6NKorl mice responded to DSS-induced colitis similar to the generally used C57BL6/N mice, thus this newly developed mouse sub-strain provides a useful animal model of IBD.

Background: As a laboratory animal resource, the ICR mouse is commonly used in a variety of research fields. However, information on differences in exercise-related characteristics in ICR mice derived from different lineages and the underlying mechanisms remains to be elucidated. In this study, we investigated the intrinsic exercise capacity and a magnitude of response to acute exercise, and sought to identify mechanisms contributing to difference in Korl:ICR (a novel ICR lineage recently established by the National Institute of Food and Drug Safety Evaluation, Korea) and two commercialized ICR lineages derived from different origins (viz., A:ICR mouse from Orient Bio Com, the United States, and B:ICR mouse from Japan SLC Inc., Japan). Results: Results showed that despite no significant difference in body weight and weight-proportioned tissue mass of heart and skeletal muscles among groups, the relatively low intrinsic exercise capacity and exaggerated response to acute exercise were identified in B:ICR comparted with Korl:ICR and A:ICR, as reflected by total work and lactate threshold (LT). Also, the mitochondrial efficiency expressed as the complex 1 and complex 1 + 2 respiratory control ratio (RCR) values for cardiac mitochondrial O 2 consumption in B:ICR was significantly lower than that in Korl:ICR with higher level of state 2 respiration by glutamate/malate and UCP3 expression in cardiac muscle. Conclusions Taken together, these results indicate that the intrinsic exercise capacity of ICR mouse varies according to lineages, suggesting the role of cardiac mitochondrial coupling efficiency as a possible mechanism that might contribute to differences in the intrinsic exercise capacity and magnitude of response to exercise.