Purpose: Due to chronic toxicity, tacrolimus-sparing is an important issue in kidney transplant recipients (KTRs). Several studies have shown that bisphosphonate use is associated with favorable graft outcomes in KTRs. We investigated whether the association between tacrolimus trough levels (TTLs) and graft outcomes differed according to bisphosphonate use in KTRs. Materials and Methods: We conducted a retrospective study encompassing 1441 KTRs who were administered tacrolimus-based immunosuppressants. The primary exposure was a time-dependent cross-product of TTLs (low TTLs vs. normal-high TTLs with a reference of 6 ng/mL) and bisphosphonate use. Two primary outcomes were evaluated: overall graft loss (death or conversion to kidney replacement) and an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m 2 . Results: During the median follow-up of 6.1 (3.4–9.7) years, overall graft loss occurred in 157 (10.9%) patients. Cox regression revealed that normal-high TTLs without bisphosphonate use were associated with a reduced risk of overall graft loss [adjusted hazard ratio (aHR), 0.65; 95% confidence interval (CI), 0.45–0.95] compared to low TTLs without bisphosphonate use. The use of bisphosphonate in conjunction with normal-high TTLs correlated with an even lower risk of overall graft loss (aHR, 0.25; 95% CI, 0.08–0.80) compared with low TTLs without bisphosphonate use. In patients with low TTLs, bisphosphonate use was associated with a reduced risk of overall graft loss compared with non-use (aHR, 0.20; 95% CI, 0.09–0.43). Similar trends were observed in the eGFR outcome. Conclusion The use of bisphosphonate was associated with favorable graft outcomes, even with low TTLs. Incorporating bisphosphonate into a conventional immunosuppressant regimen may potentially reduce tacrolimus requirement.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan, a novel potassium-competitive acid blocker, was developed for treating acid-related disorders. Pharmacokinetic and pharmacodynamic properties of fexuprazan, unlike those of proton pump inhibitors, are independent of food effect. This study aims to evaluate differences in efficacy and safety of fexuprazan in patients with erosive esophagitis (EE) according to the timing of dosing. Methods: In this multicenter, open-label noninferiority study, patients who had typical reflux symptoms with endoscopically confirmed EE were randomized 1:1 to receive fexuprazan 40 mg daily 30 minutes before or after meal. Treatment was completed after 2 weeks or 4 weeks when healing was endoscopically confirmed. The primary endpoint was the proportion of patients with healed EE confirmed by endoscopy up to week 4. Safety endpoints included treatment-emergent adverse events (TEAEs). Results: In the prior-to-meal group (n = 89) and after-meal group (n = 86), 4-week EE healing rates were 98.77% and 100.00% (difference, 0.01%; 95% CI, –0.01% to 0.04%) and 2-week EE healing rates were 95.77% and 97.14% (difference, 0.01%; 95% CI, –0.05% to 0.07%), respectively. TEAEs were 9.78% and 8.70% in the prior-to-meal group and the after-meal group, respectively. Conclusions Non-inferiority analysis revealed that taking fexuprazan after meal was non-inferior to taking fexuprazan before meals in patients with EE. The frequency of adverse events was similar between the 2 study groups. The drug is safe and effective for healing EE regardless of the timing of dosing.

Background/Aims: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis. Methods: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events. Results: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups.No significant difference was noted in the incidence of adverse drug reactions. Conclusions Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).

Purpose: The aim of this study was to evaluate the risk factors associated with glaucoma or ocular hypertension (OHT) in patients taking oral corticosteroids for extended periods, and to aid in managing intraocular pressure (IOP) in patients with these risk factors. Methods: A cross-sectional study was performed involving 690 patients who visited a tertiary referral hospital and had been using oral corticosteroids for more than six months. Patients' demographics, tonometry results, drug type, dosage, duration, ophthalmic history, and the use of glaucoma eye drops were analyzed to determine the risk factors associated with glaucoma or OHT. Results: In a generalized linear model analysis comparing patients' eyes diagnosed with glaucoma or ocular hypertension to those without such diagnoses, no statistical difference was observed between the two groups in terms of drug type, age, and duration of oral corticosteroid use. However, the dosage was found to be statistically significant (odds ratio 1.09, p = 0.0294). Conclusions No difference in the incidence of glaucoma or OHT was found based on the type of oral steroid, age, or duration of use. However, a higher incidence of glaucoma and OHT was observed among patients taking higher doses of oral steroids. Therefore, it is suggested that using lower doses of oral steroids may be more beneficial for managing IOP.

Purpose: The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory, co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TM and the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model. Materials and Methods: Intraabdominal transplant of cardiac allografts from BALB/c (H-2d ) donors to C57BL/6 (H-2b ) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitoneal route until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells and spleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay on day 7. Results: The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DX treatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4 + FOXP3+ /CD4+ CD44hi T cell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+ CD85k+ with TM/DX were observed. The inhibition of pro-inflammatory cytokine interleukin-6 was also observed. Conclusion These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/ DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survival by inducing tolerance in transplantation.

Purpose: In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. Materials and Methods: Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. Results: CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. Conclusion Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.

PURPOSE: Cardiac changes in end-stage renal disease are the most common causes of death after kidney transplantation (KT). Chronic kidney disease presents a major risk factor for the development and progression of diastolic dysfunction. The purpose of this study was to identify the association between changes in left ventricular (LV) diastolic function and perioperative clinical factors in patients with preserved ejection fraction following KT. MATERIALS AND METHODS: We reviewed 115 patients who underwent KT between January 2011 and December 2015 with both preand post-transplant echocardiograms; patients with LV systolic dysfunction were excluded. LV diastolic function was measured using the ratio of early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/e′). RESULTS: Patients with normal pre-operative LV systolic function (n=97) showed improvement in E/e′ after KT (11.9±4.4 to 10.5±3.8, p=0.023). Additionally, post-KT estimated glomerular filtration ratio was associated with changes in E/e′ (odds ratio, −0.056; 95% confidence interval, −0.014 to −0.007; p=0.026). Among patients with preexisting diastolic dysfunction (20/97 patients), the amount of intraoperative fluid administration was related to E/e′ changes (odds ratio, 0.003; 95% confidence interval, 0.000 to 0.005; p=0.029). CONCLUSION: KT is associated with improved diastolic function. Post-KT renal function was significantly related to changes in LV diastolic function. The amount of intraoperative fluid was a risk factor for worsening diastolic function after KT in patients with preexisting diastolic dysfunction.
Cause of Death ; Filtration ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Kidney ; Renal Insufficiency, Chronic ; Retrospective Studies ; Risk Factors

BACKGROUND/AIMS: The aims of the present study were to determine the frequency of interval colorectal cancers (CRCs) after surveillance colonoscopy and to compare the clinicopathologic features and survival outcomes with those of non-interval CRCs. METHODS: From January 2003 to December 2013, 66,016 follow-up colonoscopies for 38,412 patients performed within recommended time were reviewed retrospectively based on data from 11 tertiary hospitals in South Korea. To compare clinicopathologic features and survival rates for interval CRC, 106 patients with non-interval CRC matched in age and gender were included. RESULTS: Among the 66,016 colonoscopies performed within the surveillance period, 63 cases (63/66,016) of interval CRC were detected, and 53 were finally included in the analysis. The mean age was 69.9±8.8 years, and the male to female ratio was 1.94:1. Although the occurrence rate of cancer in the right side colon was higher than that of non-interval CRC, interval CRCs were predominantly left sided. Other clinicopathologic features and overall survival were not significantly different between the two groups. Missed lesion was suspected to be the most common cause (29 cases, 54.7%). CONCLUSIONS: The frequency of interval CRC among patients who had undergone a surveillance colonoscopy was 0.095%. While sharing some similar clinical features and survival outcomes, interval CRCs in Korea developed more often in males and on the left side in contrast to results from Western studies.
Colon ; Colonoscopy ; Colorectal Neoplasms* ; Female ; Follow-Up Studies ; Humans ; Korea ; Male ; Retrospective Studies ; Survival Rate ; Tertiary Care Centers