As a leading cause of chronic kidney disease, clinical demand for noninvasive biomarkers of diabetic kidney disease (DKD) beyond proteinuria is increasing. Metabolomics is a popular method to identify mechanisms and biomarkers. We investigated urinary targeted metabolomics in DKD patients. Methods: We conducted a targeted metabolomics study of 26 urinary metabolites in consecutive patients with DKD stage 1 to 5 (n = 208) and healthy controls (n = 26). The relationships between estimated glomerular filtration rate (eGFR) or urine protein-creatinine ratio (UPCR) and metabolites were evaluated. Multivariate Cox analysis was used to estimate relationships between urinary metabolites and the target outcome, end-stage renal disease (ESRD). C statistics and time-dependent receiver operating characteristics (ROC) were used to assess diagnostic validity. Results: During a median 4.5 years of follow-up, 103 patients (44.0%) progressed to ESRD and 65 (27.8%) died. The median fold changes of nine metabolites belonged to monosaccharide and tricarboxylic acid (TCA) cycle metabolites tended to increase with DKD stage. Myo-inositol, choline, and citrates were correlated with eGFR and choline, while mannose and myo-inositol were correlated with UPCR. Elevated urinary monosaccharide and TCA cycle metabolites showed associations with increased morality and ESRD progression. The predictive power of ESRD progression was high, in the order of choline, myo-inositol, and citrate. Although urinary metabolites alone were less predictive than serum creatinine or UPCR, myo-inositol had additive effect with serum creatinine and UPCR. In time-dependent ROC, myo-inositol was more predictive than UPCR of 1-year ESRD progression prediction. Conclusion: Myo-inositol can be used as an additive biomarker of ESRD progression in DKD.

Purpose: To compare the clinical outcomes of penetrating keratoplasty (PKP) and Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with Glaucoma Ahmed Valve implants. Methods: The charts of 11 patients who underwent PKP and 11 who underwent DSAEK between February 2016 and June 2018 were retrospectively reviewed; all patients previously underwent Ahmed valve implant surgery. The best corrected visual acuity, intraocular pressure, and endothelial cell count were compared 1, 3, and 6 months after surgery. Graft rejection and graft failure were also evaluated during follow-up. The survival rates were compared using Kaplan–Meier survival analysis. Results: The difference in graft survival rates of the PKP and DSAEK groups was not significant (p = 0.295); however, graft failure occurred earlier in the PKP group (12.9 ± 10.1 vs. 18.8 ± 5.3 months). The postoperative best corrected visual acuity of the PKP group had improved at 1 (p = 0.027) and 3 (p = 0.017) months, while the DSAEK group showed significant improvement at 1, 3, and 6 months (all p = 0.005). Intergroup analysis showed better visual prognosis of the DSAEK group at 1, 3, and 6 months after surgery (p = 0.023, p = 0.007, and p = 0.004, respectively). Conclusions In our study, the two corneal transplantation methods did not have significantly different graft survival rates; however, graft failure occured later in the DSAEK group and the postoperative visual acuity was better than in the PKP group. Although further study is needed, performing DSAEK in patients with an Ahmed valve implant seems to be a good alternative to PKP.

Purpose: Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. Methods: The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. Results: Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. Conclusions TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

Purpose: We compare the clinical outcomes of femtosecond-laser penetrating keratoplasty and penetrating keratoplasty performed using a manual trephine. Methods: The clinical outcomes of 21 eyes that underwent penetrating keratoplasty using a manual trephine and 29 eyes that underwent femtosecond-laser penetrating keratoplasty were compared in terms of best-corrected visual acuity, refractive and corneal astigmatisms, endothelial cell counts, and graft rejection and failure. Results: The best-corrected visual acuities measured 1, 3, 6, 12, and 18 months after surgery were logMAR 1.21, 1.28, 1.25, 1.14, and 1.43 for the manual trephine group and logMAR 0.82, 0.71, 0.78, 0.49, and 0.56 for the femtosecond-laser group; the latter group thus exhibited better visual acuity at all times. The refractive astigmatism values were 5.13, 6.35, 5.28, 5.18, and 6.36 diopters (D) for the manual trephine group and 6.09, 6.33, 5.14, 5.23, and 4.89 D for the femtosecond-laser group. The corneal astigmatism values were 5.40, 6.45, 6.30, 5.64, and 5.78 D for the manual trephine group and 6.17, 6.24, 5.72, 5.02, and 4.83 D for the femtosecond-laser group. The refractive astigmatism was significantly lower at 18 months after surgery and the corneal astigmatism was significantly lower at both 12 and 18 months after surgery in the femtosecond-laser group. None of endothelial cell count, graft rejection or failure rate, differed significantly between the two groups. Conclusions Femtosecond-laser-enabled keratoplasty affords better visual recovery, less refractive and corneal astigmatism, and better wound stability than does penetrating keratoplasty using a manual trephine.

Objectives: The current study aimed to investigate whether pregnancy outcomes are affected by maternal rhesus (Rh) status by comparing the primigravida pregnancy outcomes of Rh-negative women with those of Rh-positive women. Methods: The study data were collected from the Korea National Health Insurance Claims Database and the National Health Screening Program for Infants and Children. In total, 1,664,882 primigravida women who gave birth between January 1, 2007 and December 31, 2014, were enrolled in this study. As the risk and severity of sensitization response increases with each subsequent pregnancy, only primigravida women were enrolled. The patients were divided into 2 groups according to Rh status, and the pregnancy outcomes were compared. Results: In total, 1,661,320 women in the Rh-positive group and 3,290 in the Rh-negative group were assessed. With regard to adverse pregnancy outcomes, there was no statistically significant difference between the 2 groups in terms of the prevalence of preeclampsia, postpartum hemorrhage, abruptio placenta, placenta previa, and uterine artery embolization. A univariate analysis revealed that none of the adverse pregnancy outcomes were significantly correlated to Rh status (preeclampsia: odds ratio [OR], 1.00, 95% confidence interval [CI], 0.81–1.23; postpartum hemorrhage: OR, 1.10, 95% CI, 0.98–1.24; abruptio placenta: OR, 0.80, 95% CI, 0.46–1.37; and placenta previa: OR, 1.08, 95% CI, 0.78–1.42). The adjusted ORs of postpartum hemorrhage and preterm birth did not significantly differ. Conclusion Maternal Rh status is not associated with adverse outcomes in primigravida women.

Objective: The aim of this survey was to investigate the recommendations and clinical practice patterns of the Korean Society of Maternal and Fetal Medicine (KSMFM) members, regarding management of isolated oligohydramnios (IO). Methods: From December 2018 to February 2019, questionnaires were e-mailed to the KSMFM members at 257 institutes that are listed by the Korean Statistical Information Services (KOSIS) as suitable labor premises. Responses to the seven questions on the management of IO, from diagnosis to treatment, were evaluated. Results: A total of 72 KSMFM members responded to this survey. Nearly all participants (90.1%) used the amniotic fluid index (AFI) as the primary method for estimating amniotic fluid volume. The majority of the participants (73.6%) believed that IO was a risk factor for adverse pregnancy outcomes, including abnormal fetal heart rate (73.6%), need for cesarean delivery (58.3%), intrauterine fetal demise (52.8%), and meconium aspiration syndrome (50%). Almost 70% of the participants believed that induction of labor might decrease perinatal morbidities, and that late-preterm to early-term period (36–38 gestational weeks) was a suitable timeframe for delivery, if the fetus was sufficiently grown and antenatal testing revealed reassuring results. Less than half of the participants (47.2%) believed that maternal oral or intravenous hydration was a useful intervention for IO management. Conclusions KSMFM members preferred labor induction at late-preterm to early-term, to decrease perinatal morbidity in cases of IO, although it was still uncertain whether labor induction improved the outcomes. Further prospective studies are needed regarding IO management.

Purpose: Cold air is a major environmental factor that exacerbates asthma. Transient receptor potential melastatin family member 8 (TRPM8) is a cold-sensing channel expressed in the airway epithelium. However, its role in airway inflammation remains unknown. We investigated the role of TRPM8 in innate immune responses in bronchial epithelial cells and asthmatic subjects. Methods: The TRPM8 mRNA and protein expression on BEAS2B human bronchial epithelial cells was examined by real-time polymerase chain reaction (PCR), immunofluorescence staining and western blotting. Additionally, interleukin (IL)-4, IL-6, IL-8, IL-13, IL-25 and thymic stromal lymphopoietin (TSLP) levels before and after menthol, dexamethasone and N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl) piperazine-1-carboxamide (BCTC) treatments were measured via real-time PCR. TRPM8 protein levels in the supernatants of induced sputum from asthmatic subjects and normal control subjects were measured using enzyme-linked immunosorbent assay, and mRNA levels in sputum cell lysates were measured using real-time PCR. Results: Treatment with up to 2 mM menthol dose-dependently increased TRPM8 mRNA and protein in BEAS2B cells compared to untreated cells (P < 0.001) and concomitantly increased IL-25 and TSLP mRNA (P < 0.05), but not IL-33 mRNA. BCTC (10 μM) significantly abolished menthol-induced up-regulation of TRPM8 mRNA and protein and IL-25 and TSLP mRNA (P < 0.01). TRPM8 protein levels were higher in the supernatants of induced sputum from asthmatic subjects (n = 107) than in those from healthy controls (n = 19) (P < 0.001), and IL-25, TSLP and IL-33 mRNA levels were concomitantly increased (P < 0.001). Additionally, TRPM8 mRNA levels correlated strongly with those of IL-25 and TSLP (P < 0.001), and TRPM8 protein levels were significantly higher in bronchodilator-responsive asthmatic subjects than in nonresponders. Conclusions TRPM8 may be involved in the airway epithelial cell innate immune response and a molecular target for the treatment of asthma.

Purpose: We compare the clinical outcomes of femtosecond-laser penetrating keratoplasty and penetrating keratoplasty performed using a manual trephine. Methods: The clinical outcomes of 21 eyes that underwent penetrating keratoplasty using a manual trephine and 29 eyes that underwent femtosecond-laser penetrating keratoplasty were compared in terms of best-corrected visual acuity, refractive and corneal astigmatisms, endothelial cell counts, and graft rejection and failure. Results: The best-corrected visual acuities measured 1, 3, 6, 12, and 18 months after surgery were logMAR 1.21, 1.28, 1.25, 1.14, and 1.43 for the manual trephine group and logMAR 0.82, 0.71, 0.78, 0.49, and 0.56 for the femtosecond-laser group; the latter group thus exhibited better visual acuity at all times. The refractive astigmatism values were 5.13, 6.35, 5.28, 5.18, and 6.36 diopters (D) for the manual trephine group and 6.09, 6.33, 5.14, 5.23, and 4.89 D for the femtosecond-laser group. The corneal astigmatism values were 5.40, 6.45, 6.30, 5.64, and 5.78 D for the manual trephine group and 6.17, 6.24, 5.72, 5.02, and 4.83 D for the femtosecond-laser group. The refractive astigmatism was significantly lower at 18 months after surgery and the corneal astigmatism was significantly lower at both 12 and 18 months after surgery in the femtosecond-laser group. None of endothelial cell count, graft rejection or failure rate, differed significantly between the two groups. Conclusions Femtosecond-laser-enabled keratoplasty affords better visual recovery, less refractive and corneal astigmatism, and better wound stability than does penetrating keratoplasty using a manual trephine.

Objectives: The current study aimed to investigate whether pregnancy outcomes are affected by maternal rhesus (Rh) status by comparing the primigravida pregnancy outcomes of Rh-negative women with those of Rh-positive women. Methods: The study data were collected from the Korea National Health Insurance Claims Database and the National Health Screening Program for Infants and Children. In total, 1,664,882 primigravida women who gave birth between January 1, 2007 and December 31, 2014, were enrolled in this study. As the risk and severity of sensitization response increases with each subsequent pregnancy, only primigravida women were enrolled. The patients were divided into 2 groups according to Rh status, and the pregnancy outcomes were compared. Results: In total, 1,661,320 women in the Rh-positive group and 3,290 in the Rh-negative group were assessed. With regard to adverse pregnancy outcomes, there was no statistically significant difference between the 2 groups in terms of the prevalence of preeclampsia, postpartum hemorrhage, abruptio placenta, placenta previa, and uterine artery embolization. A univariate analysis revealed that none of the adverse pregnancy outcomes were significantly correlated to Rh status (preeclampsia: odds ratio [OR], 1.00, 95% confidence interval [CI], 0.81–1.23; postpartum hemorrhage: OR, 1.10, 95% CI, 0.98–1.24; abruptio placenta: OR, 0.80, 95% CI, 0.46–1.37; and placenta previa: OR, 1.08, 95% CI, 0.78–1.42). The adjusted ORs of postpartum hemorrhage and preterm birth did not significantly differ. Conclusion Maternal Rh status is not associated with adverse outcomes in primigravida women.

Objective: The aim of this survey was to investigate the recommendations and clinical practice patterns of the Korean Society of Maternal and Fetal Medicine (KSMFM) members, regarding management of isolated oligohydramnios (IO). Methods: From December 2018 to February 2019, questionnaires were e-mailed to the KSMFM members at 257 institutes that are listed by the Korean Statistical Information Services (KOSIS) as suitable labor premises. Responses to the seven questions on the management of IO, from diagnosis to treatment, were evaluated. Results: A total of 72 KSMFM members responded to this survey. Nearly all participants (90.1%) used the amniotic fluid index (AFI) as the primary method for estimating amniotic fluid volume. The majority of the participants (73.6%) believed that IO was a risk factor for adverse pregnancy outcomes, including abnormal fetal heart rate (73.6%), need for cesarean delivery (58.3%), intrauterine fetal demise (52.8%), and meconium aspiration syndrome (50%). Almost 70% of the participants believed that induction of labor might decrease perinatal morbidities, and that late-preterm to early-term period (36–38 gestational weeks) was a suitable timeframe for delivery, if the fetus was sufficiently grown and antenatal testing revealed reassuring results. Less than half of the participants (47.2%) believed that maternal oral or intravenous hydration was a useful intervention for IO management. Conclusions KSMFM members preferred labor induction at late-preterm to early-term, to decrease perinatal morbidity in cases of IO, although it was still uncertain whether labor induction improved the outcomes. Further prospective studies are needed regarding IO management.