Congenital central hypoventilation syndrome in korea: 20 years of clinical observation and evaluation of the ventilation strategy in a single center.

Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder characterized by hypoventilation due to impaired breathing control by the central nervous system and other symptoms of autonomic dysfunction. Mutations in paired-like homeobox 2 B (PHOX2B) are responsible for most cases of CCHS. Patients with CCHS have various phenotypes and severities, making the diagnosis difficult. This study aimed to present a comprehensive single-center experience of patients with CCHS, including key clinical features, treatment strategies, and outcomes. A retrospective chart review was performed for patients diagnosed with CCHS between January 2001 and July 2023 at Seoul National University Children's Hospital. Finally, we selected 24 patients and collected their demographic data, genotypes, ventilation methods, and clinical features related to autonomic dysfunction. The relationship between the clinical manifestations and genotypes was also examined. All patients used home ventilators, and tracheostomy was performed in 87.5% of patients. Fifteen (62.5%) patients had constipation and nine (37.5%) were diagnosed with Hirschsprung disease. Arrhythmia, endocrine dysfunction, and subclinical hypothyroidism were present in nine (37.5%), six patients (25.0%), and two patients (16.7%), respectively. A significant number of patients exhibited neurodevelopmental delays (19 patients, 79.2%). There was a correlation between the phenotype and genotype of PHOX2B in patients with CCHS. (r = 0.71, p < 0.001).   Conclusion: There was a positive correlation between paired-like homeobox 2 B mutations (especially the number of GCN repeats in the polyalanine repeat mutations sequence) and clinical manifestations. This study also demonstrated how initial treatment for hypoventilation affects neurodevelopmental outcomes in patients with CCHS. What is Known: • Congenital central hypoventilation syndrome is a rare genetic disorder characterized by hypoventilation and dysfunction of autonomic nervous system. • The disease-defining gene of CCHS is PHOX2B gene - most of the cases have heterozygous PARMs and the number of GCN triplets varies among the patients(20/24 - 20/33). What is New: • We have noted in the Korean patients with CCHS that there is a correlation between genotype (number of GCN repeats) and severity of phenotype. • National support for rare diseases allowed for a prompter diagnosis of patients with CCHS in Korean population.

Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.

The role of the serine/glycine metabolic pathway (SGP) has recently been demonstrated in tumors; however, the pathological relevance of the SGP in thyroid cancer remains unexplored. Here, we perform metabolomic profiling of 17 tumor-normal pairs; bulk transcriptomics of 263 normal thyroid, 348 papillary, and 21 undifferentiated thyroid cancer samples; and single-cell transcriptomes from 15 cases, showing the impact of mitochondrial one-carbon metabolism in thyroid tumors. High expression of serine hydroxymethyltransferase-2 (SHMT2) and methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is associated with low thyroid differentiation scores and poor clinical features. A subpopulation of tumor cells with high mitochondrial one-carbon pathway activity is observed in the single-cell dataset. SHMT2 inhibition significantly compromises mitochondrial respiration and decreases cell proliferation and tumor size in vitro and in vivo. Collectively, our results highlight the importance of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer and suggest that SHMT2 is a potent therapeutic target.

Association between circulating ECM-associated molecules and cardiovascular outcomes in hemodialysis patients: a multicenter prospective cohort study.

Hemodialysis patients are susceptible to cardiovascular remodeling, which increases the risk of cardiovascular morbidity and mortality. Circulating extracellular matrix (ECM)-associated molecules increase during cardiovascular remodeling and can be potential biomarkers of adverse cardiovascular outcomes. However, their clinical significance in patients undergoing hemodialysis remain unclear. This study aimed to elucidate the association between circulating ECM-associated molecules and cardiovascular outcomes in patients undergoing hemodialysis. To this end, we measured levels of plasma matrix metalloproteinase (MMP)-2, MMP-9, tenascin-C, and thrombospondin-2 in 372 patients with hemodialysis. Plasma MMP-2 levels were significantly higher in patients with future cardiovascular events than in those without future cardiovascular events (P = 0.004). All measured molecules had significant correlations with amino-terminal pro-brain natriuretic peptide levels, but the correlation coefficient was the strongest for plasma MMP-2 (rho = 0.317, P < 0.001). High plasma MMP-2 levels were predictive of left ventricular (LV) diastolic dysfunction (adjusted odds ratio per a standard deviation increase = 1.48, 95% confidence interval [CI] = 1.05-2.08) and were independently associated with an increased risk of composite cardiovascular events (adjusted hazard ratio per a standard deviation increase = 1.30, 95% CI = 1.04-1.63). In conclusion, high plasma MMP-2 levels are associated with LV diastolic dysfunction and an increased risk of adverse cardiovascular outcomes in hemodialysis patients.

Hemosiderin induced acute kidney injury requiring hemodialysis in patients with paroxysmal nocturnal hemoglobinuria: A case report.

RATIONALE: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disease with features of hemolytic anemia, thrombosis, and bone marrow failure. Due to intravascular hemolysis and hemoglobinuria, renal dysfunction is often accompanied in PNH patients. PATIENT CONCERNS: A 25-year old woman presenting gross hematuria after coronavirus disease 2019 infection was admitted to our medical center. She had mild nausea and headache. She was diagnosed with iron deficiency anemia few years ago and had no other underlying disease. Her laboratory findings showed acute kidney injury (AKI) and severe anemia, with evidences of hemolysis. DIAGNOSIS: Renal biopsy was done to determine the cause of renal failure and the result was acute tubular necrosis with deposition of golden pigments, hemosiderin. With pathologic result and laboratory finding of hemolysis, we did flow cytometry for PNH, and the patient was finally diagnosed with PNH. INTERVENTIONS: With AKI and oliguria, the patient started to take hemodialysis. OUTCOMES: After taking 5 sessions of hemodialysis, the patient's renal function was recovered from AKI. With diagnosis of PNH, the patient is now being treated with complement C5 inhibitor. LESSONS: This challenging case tells us that we should consider the first manifestation of PNH as a cause of severe AKI requiring hemodialysis in a patient with anemia and evidence of hemolysis.

Single-Walled Carbon Nanotube-Guided Topical Skin Delivery of Tyrosinase to Prevent Photoinduced Damage.

When the skin is exposed to ultraviolet radiation (UV), it leads to the degradation of the extracellular matrix (ECM) and results in inflammation. Subsequently, melanocytes are triggered to induce tyrosinase-mediated melanin synthesis, protecting the skin. Here, we introduce a proactive approach to protect the skin from photodamage via the topical delivery of Streptomyces avermitilis-derived tyrosinase (SaTy) using single-walled carbon nanotube (SWNT). Utilizing a reverse electrodialysis (RED) battery, we facilitated the delivery of SaTy-SWNT complexes up to depths of approximately 300 µm, as analyzed by using confocal Raman microscopy. When applied to ex vivo porcine skin and in vivo albino mouse skin, SaTy-SWNT synthesized melanin, resulting in 4-fold greater UV/vis absorption at 475 nm than in mice without SaTy-SWNT. The synthesized melanin efficiently absorbed UV light and alleviated skin inflammation. In addition, the densification of dermal collagen, achieved through SaTy-mediated cross-linking, reduced photoinduced wrinkles by 66.3% in the affected area. Our findings suggest that SWNT-mediated topical protein delivery holds promise in tissue engineering applications.

Antibody response in patients undergoing chronic hemodialysis post-severe acute respiratory syndrome coronavirus 2 vaccination: A prospective observational study.

Vaccination is important for patients undergoing hemodialysis (HD) to prevent coronavirus disease 2019 (COVID-19) infection since they are more vulnerable. However, they exhibit a weak response to vaccines, underscoring the importance of understanding whether antibodies are sufficiently produced and their durability post-COVID-19 vaccination. This prospective observational study assessed the antibody response of Korean patients undergoing HD for 1 year. We compared the antibody responses of patients undergoing HD to the COVID-19 vaccine with those of healthy volunteers from 2021 to 2022. The patient and control groups received 2 doses of ChAdOx1 nCoV-19 and mRNA-1273, respectively. Immunoglobulin G (IgG) and neutralizing antibody levels were measured weeks or months apart after 2 doses for 1 year using enzyme-linked immunosorbent and fluorescence-based competitive severe acute respiratory syndrome coronavirus 2 neutralizing assays, respectively. We analyzed the third dose's effect on the patient group by categorizing the group into patients who received the third dose and those who did not since it was initiated midway through the study. In the control group, we enrolled participants who had completed 3 doses of mRNA-1273 since almost all participants received the third dose. Thirty-two patients undergoing HD and 15 healthy participants who received 2 doses of ChAdOx1 nCoV-19 and 3 of mRNA-1273, respectively, were enrolled. Although antibody production was weaker in the patient group than in the control group (P < .001), patients showed an increase in IgG levels (0.408 ± 0.517 optical density (OD) pre-vaccination, 2.175 ± 1.241 OD in patients with 2 doses, and 2.134 ± 1.157 OD in patients with 3 doses 1 year after the second dose) and neutralizing antibodies (23 ± 8% pre-vaccination, 87 ± 23% in patients with 2 doses, and 89 ± 18% in patients with 3 doses 1 year after the second dose) post-vaccination (P < .001). In the patient group, 19 patients received a third dose (BNT162b2 or mRNA-1273); however, it did not increase the antibody levels (P = 1.000). Furthermore, the antibodies produced by the vaccination did not wane until 1 year. Two doses of vaccination resulted in a significant antibody response in patients undergoing HD, and antibody levels did not wane until 1 year.

Antibody response to COVID-19 vaccination in patients on chronic hemodialysis.

Purpose: Since patients on hemodialysis (HD) are known to be vulnerable to coronavirus disease 2019 (COVID-19), many studies were conducted regarding the effectiveness of the COVID-19 vaccine in HD patients in Western countries. Here, we assessed antibody response of HD patients for 6 months post-vaccination to identify the duration and effectiveness of the COVID-19 vaccine in the Asian population. Materials and Methods: We compared antibody response of the COVID-19 vaccine in HD patients with healthy volunteers. Patient and control groups had two doses of ChAdOx1 nCoV-19 and mRNA-1273, respectively. Immunoglobulin G (IgG) was measured before vaccination, 2 weeks after the first dose, 2 and 4 weeks, 3 and 6 months after the second dose. Neutralizing antibody was measured before vaccination and at 2 weeks, 3 and 6 months after second dose. Since the third dose was started in the middle of the study, we analyzed the effect of the third dose as well. Results: Although antibody production was weaker than the control group (n=22), the patient group (n=39) showed an increase in IgG and neutralizing antibody after two doses. And, 21/39 patients and 14/22 participants had a third dose (BNT162b2 or mRNA-1273 in the patient group, mRNA-1273 in the control group), and it did not affect antibody response in both group. Trend analysis showed IgG and neutralizing antibody did not decrease over time. Age, sex, and HD vintage did not affect antibody production in HD patients. Patients with higher body mass index displayed better seroresponse, while those on immunosuppressants showed poor seroresponse. Conclusion: Two doses of vaccination led to significant antibody response in HD patients, and the antibody did not wane until 6 months.

Plasma Interleukin-6 Level Predicts the Risk of Arteriovenous Fistula Dysfunction in Patients Undergoing Maintenance Hemodialysis.

Systemic inflammation has been proposed as a relevant factor of vascular remodeling and dysfunction. We aimed to identify circulating inflammatory biomarkers that could predict future arteriovenous fistula (AVF) dysfunction in patients undergoing hemodialysis. A total of 282 hemodialysis patients were enrolled in this prospective multicenter cohort study. Plasma cytokine levels were measured at the time of data collection. The primary outcome was the occurrence of AVF stenosis and/or thrombosis requiring percutaneous transluminal angioplasty or surgery within the first year of enrollment. AVF dysfunction occurred in 38 (13.5%) patients during the study period. Plasma interleukin-6 (IL-6) levels were significantly higher in patients with AVF dysfunction than those without. Diabetes mellitus, low systolic blood pressure, and statin use were also associated with AVF dysfunction. The cumulative event rate of AVF dysfunction was the highest in IL-6 tertile 3 (p = 0.05), and patients in tertile 3 were independently associated with an increased risk of AVF dysfunction after multivariable adjustments (adjusted hazard ratio = 3.06, p = 0.015). In conclusion, circulating IL-6 levels are positively associated with the occurrence of incident AVF dysfunction in hemodialysis patients. Our data suggest that IL-6 may help clinicians identify those at high risk of impending AVF failure.

In vivo surface-enhanced Raman scattering nanosensor for the real-time monitoring of multiple stress signalling molecules in plants.

When under stress, plants release molecules to activate their defense system. Detecting these stress-related molecules offers the possibility to address stress conditions and prevent the development of diseases. However, detecting endogenous signalling molecules in living plants remains challenging due to low concentrations of these analytes and interference with other compounds; additionally, many methods currently used are invasive and labour-intensive. Here we show a non-destructive surface-enhanced Raman scattering (SERS)-based nanoprobe for the real-time detection of multiple stress-related endogenous molecules in living plants. The nanoprobe, which is placed in the intercellular space, is optically active in the near-infrared region (785 nm) to avoid interferences from plant autofluorescence. It consists of a Si nanosphere surrounded by a corrugated Ag shell modified by a water-soluble cationic polymer poly(diallyldimethylammonium chloride), which can interact with multiple plant signalling molecules. We measure a SERS enhancement factor of 2.9 × 107 and a signal-to-noise ratio of up to 64 with an acquisition time of ~100 ms. To show quantitative multiplex detection, we adopted a binding model to interpret the SERS intensities of two different analytes bound to the SERS hot spot of the nanoprobe. Under either abiotic or biotic stress, our optical nanosensors can successfully monitor salicylic acid, extracellular adenosine triphosphate, cruciferous phytoalexin and glutathione in Nasturtium officinale, Triticum aestivum L. and Hordeum vulgare L.-all stress-related molecules indicating the possible onset of a plant disease. We believe that plasmonic nanosensor platforms can enable the early diagnosis of stress, contributing to a timely disease management of plants.

Clinical outcomes following robotic versus conventional DIEP flap in breast reconstruction: A retrospective matched study.

Background: A robotic deep inferior epigastric perforator (DIEP) flap created through a totally extraperitoneal approach minimizes violation of the donor site, which may lead to postoperative pain reduction and rapid recovery. The authors compared the clinical outcomes of robotic and conventional DIEP flap breast reconstructions. Methods: Data from consecutive patients who underwent mastectomy with DIEP flaps for breast reconstruction between July 2017 and January 2021 were retrospectively reviewed. Patients were divided into robotic and conventional DIEP groups, and the two groups were matched using the inverse probability of treatment weighting method. They were compared based on the reconstruction time, drainage amount, postoperative pain, rescue analgesics, hospital stay, complications, and BREAST-Q scores. Results: After matching, a dataset of 207 patients was formed, including 21 patients in the robotic DIEP group and 186 patients in the conventional DIEP group. The mean reconstruction time was longer in the robotic DIEP group than in the conventional DIEP group (P<0.001). In the robotic group, pain intensity during the postoperative 6-24 hours was significantly reduced (P=0.001) with less use of fentanyl (P=0.003) compared to the conventional DIEP group. The mean length of hospital stay for the robotic DIEP group was shorter than that for conventional DIEP (P=0.002). BREAST-Q scores indicated a higher level of the abdominal physical well-being domain in the robotic group (P=0.020). Complication rates were comparable between the two groups. Conclusions: This study suggests that a robotic DIEP flap offers enhanced postoperative recovery, accompanied by a reduction in postoperative pain and hospital stay.

Comparison of Postoperative Gastrointestinal Motility of Sugammadex and Neostigmine in Patients Undergoing Robotic Thyroidectomy: A Retrospective Study.

Postoperative bowel dysfunction poses difficulty to patients during their recovery from surgery, and reversal agents may affect bowel function. This study aimed to investigate and compare the effects of sugammadex and a neostigmine/glycopyrrolate combination on postoperative bowel movement in patients undergoing robotic thyroidectomy. The electronic medical records of 122 patients, who underwent robotic thyroidectomy between March 2018 and December 2020, were retrospectively reviewed. Demographic, clinical, and laboratory findings and the first gas-passing time after surgery were assessed. The number of patients with a first gas emission time over 24 h was significantly higher in the neostigmine group than in the sugammadex group (p = 0.008). Multivariate logistic regression analysis indicated that sugammadex was a prognostic factor for the first gas-passing time within 24 h (odds ratio = 4.60, 95% confidence interval 1.47-14.36, p = 0.005). Although postoperative bowel motility, based on the first gas emission time, was comparable, the number of patients with a first gas emission time within 24 h was significantly higher in the sugammadex group than in the neostigmine group. This shows that the use of sugammadex did not affect the delayed recovery of postoperative bowel motility after robotic thyroidectomy.

Novel Cocrystals of Vonoprazan: Machine Learning-Assisted Discovery.

Vonoprazan (VPZ) is the first-in-class potassium-competitive acid blocker (P-CAB), and has many advantages over proton pump inhibitors (PPIs). It is administered as a fumarate salt for the treatment of acid-related diseases, including reflux esophagitis, gastric ulcer, and duodenal ulcer, and for eradication of Helicobacter pylori. To discover novel cocrystals of VPZ, we adopted an artificial neural network (ANN)-based machine learning model as a virtual screening tool that can guide selection of the most promising coformers for VPZ cocrystals. Experimental screening by liquid-assisted grinding (LAG) confirmed that 8 of 19 coformers selected by the ANN model were likely to create new solid forms with VPZ. Structurally similar benzenediols and benzenetriols, i.e., catechol (CAT), resorcinol (RES), hydroquinone (HYQ), and pyrogallol (GAL), were used as coformers to obtain phase pure cocrystals with VPZ by reaction crystallization. We successfully prepared and characterized three novel cocrystals: VPZ-RES, VPZ-CAT, and VPZ-GAL. VPZ-RES had the highest solubility among the novel cocrystals studied here, and was even more soluble than the commercially available fumarate salt of VPZ in solution at pH 6.8. In addition, novel VPZ cocrystals had superior stability in aqueous media than VPZ fumarates, demonstrating their potential for improved pharmaceutical performance.

Characteristics of fracture in patients who firstly starts kidney replacement therapy in Korea: a retrospective population-based study.

The incidence of fractures in patients with end-stage kidney disease (ESKD) is high which is associated with high morbidity and mortality. Since fractures are preventable diseases to some extent, epidemiologic studies are needed a lot. The aim of this study is to explore the epidemiology of fractures by modality of kidney replacement therapy (KRT). We performed a retrospective analysis of 52,777 patients dependent on KRT from 2008 to 2017 using the National Health Insurance System of Republic Korea. Fractures were occurred in 8995 (17.04%) of 52,777 patients with ESKD. Hemodialysis and kidney transplant patients had the highest (57.4 per 1000 person-year) and the lowest (25.2 per 1000 person-year) incidence rate, respectively. The two most common fracture sites were the lower limb and upper limb, regardless of KRT modality. The first fractures were about 2.55 ± 2.07 years after KRT initiation, the earliest in Hemodialysis patients. Diabetes mellitus, cerebrovascular disease, chronic lung and liver disease were risk factors of fractures. The use of steroids, anti-osteoporosis medications, and some classes of psychotropics and opioids was associated with an elevated risk. The results of this study inform the understanding of fractures in KRT patients.

Mental illness in patients with end-stage kidney disease in South Korea: a nationwide cohort study.

BACKGROUND: The limited literature on mental illness in end-stage kidney disease (ESKD) patients suggests that this disease is common and burdensome but underrecognized in clinical practice. This study aimed to analyze the prevalence of mental illness in ESKD patients. METHODS: We assessed the prevalence and patterns of mental illnesses in a nationwide cohort of patients diagnosed with ESKD between January 1, 2008, and December 31, 2017. The risk of mental illness was evaluated using a multivariable Cox proportional hazards model. RESULTS: A total of 70,079 patients met all study inclusion criteria. A total of 28.3% of patients had mental illness, and the specific distribution was as follows: depression, 16.8%; anxiety, 20.0%; somatoform/conversion disorder, 0.9%; stress reaction/adjustment disorder, 2.5%; and substance abuse disorder, 0.6%. The frequency of mental illness was highest in patients on hemodialysis (HD), followed by patients on peritoneal dialysis (PD) and kidney transplant (KT) patients. The peak rate of mental illness in HD and PD patients was reached 1 to 2 years after renal replacement therapy initiation, but the peak rate of most mental illnesses in KT patients occurred before surgery. The prevalence of depression was 2.19 times higher in HD patients and 1.97 times higher in PD patients than in KT patients. CONCLUSION: ESKD patients are at high risk of mental illness, and the prevalence of mental illness is highest in HD patients. Since the onset of mental illness occurs around the initiation of renal replacement therapy, clinicians need to pay attention to mental illness when treating ESKD patients.

Characterization of Medication Trends for Chronic Kidney Disease: Mineral and Bone Disorder Treatment Using Electronic Health Record-Based Common Data Model.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage (p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.

MAGEH1 interacts with GADD45G and induces renal tubular cell apoptosis.

BACKGROUND: Melanoma-associated antigen H1 (MAGEH1) is a protein that belongs to melanoma-associated antigen (MAGE) superfamily. Growth arrest and DNA damage 45G (GADD45G) is a member of the DNA damage-inducible gene family which responds to environmental stresses. We have previously shown that GADD45G is a protein that promotes apoptosis of renal tubular cells in response to a nephrotoxic injury. In this study, we show evidence that MAGEH1 interacts with GADD45G and is involved in the induction of nephrotoxin-induced apoptosis of renal tubular cells. METHODS: Primary human renal tubular epithelial (HRE) cells and human kidney 2 (HK-2) cells were used in this study. To produce stable cell lines in which MAGEH1 expression was silenced, HRE cells were transduced with a lentiviral vector encoding a single guide RNA construct targeting the MAGEH1 gene. To knockdown GADD45G expression in HRE cells, a vector containing short hairpin RNA (shRNA) was used. We used short interfering RNAs (siRNA) to achieve transient silencing of genes in HK-2 cells. Recombinant adenoviruses were synthesized to overexpress MAGEH1 and GADD45G proteins. Human protein microarray was used to identify proteins that binds to GADD45G. Co-immunoprecipitation assays were then performed to confirm microarray results. Cell death was induced by cyclosporine A (CsA). Real-time quantitative PCR assay was used to evaluate gene expression levels. The degree of apoptosis and necrosis of cultured cells was evaluated by flow cytometry. Expression levels of caspases were examined using western blot analysis. RESULTS: We found that GADD45G bound to one protein spotted in the protein microarray, which was subsequently identified as MAGEH1. We confirmed the interaction between GADD45G and MAGEH1 protein using the co-immunoprecipitation assay. MAGEH1 gene expression was not altered by CsA-induced cytotoxic injury, whereas GADD45G gene expression was increased significantly upon CsA treatment. MAGEH1 expression was significantly downregulated in GADD45G knockdown HRE stable cells suggesting that MAGEH1 expression may be dependent on GADD45G expression. CsA-induced apoptosis was significantly reduced in MAGEH1 knockdown HRE stable cells which led to an increased survival of these cells. Similar results were observed in GADD45G knockdown HRE stable cells. Accordingly, CsA-induced apoptosis was significantly decreased in MAGEH1 siRNA and GADD45G siRNA transfected HK-2 cells. CsA-induced activation of caspase-7 and caspase-9 was inhibited in MAGEH1 knockdown HRE stable cells, and similarly in GADD45G knockdown HRE stable cells. CONCLUSIONS: To the best of our knowledge, this is the first study to show that MAGEH1 interacts with GADD45G and that MAGEH1 is involved in caspase-dependent apoptosis of renal tubular cells induced by nephrotoxic drugs.

Preexisting comorbidities are associated with the mortality rate as well as the predialysis adverse events in incident dialysis patients.

BACKGROUND: Optimal estimated glomerular filtration rate (eGFR) to start maintenance dialysis is controversial. Observational studies have reported that initiation of dialysis at high eGFRs is associated with worse postdialysis survival. METHODS: We retrospectively investigated 1,038 incident dialysis patients who started maintenance dialysis during 2010-2015. Patients were assessed for comorbidities and adverse events during the transitional period of dialysis initiation. Patients were classified as planned dialysis (PD) vs. unplanned dialysis (UD) according to indications for dialysis initiation. RESULTS: UD group comprised 352 patients (33.9%). Mean eGFR at dialysis initiation was higher in UD patients than PD patients (7.9 ± 5.1 vs. 5.9 ± 3.4 mL/min/1.73 m2, p < 0.001). Mean Davies comorbidity index in the UD group was higher (vs. PD group, 1.3 ± 1.0 vs. 0.9 ± 1.0, p < 0.001). Patients with more comorbidities experienced more ischemic heart disease (hazard ratio [HR], 4.36; 95% confidence interval [CI], 1.71-11.14) in the medium-risk group and HR of 8.84 (95% CI, 3.06-25.55) in the high-risk group (vs. low-risk group, p < 0.001)) during the predialysis period. High-risk group had increased postdialysis mortality (HR, 2.48; 95% CI, 1.46-4.20; p = 0.001). Adjusted HR of mortality was higher in the medium-risk group of UD patients (HR, 1.72; 95% CI, 1.16-2.56; p = 0.007). CONCLUSION: Patients with more comorbidities were at increased risk of predialysis ischemic heart disease and postdialysis mortality. UD patients in the medium-risk population had increased risk of postdialysis mortality. Dialysis start should be individualized by considering comorbidities.

Epidemiological characteristics of cancers in patients with end-stage kidney disease: a Korean nationwide study.

Patients with end-stage kidney disease (ESKD) have been reported to have an increased risk of cancer. However, the epidemiological characteristics of cancer in ESKD patients remain unclear. Therefore, this study aimed to investigate the epidemiological characteristics of cancer in ESKD patients and the differences based on the renal replacement therapy provided. Data on ESKD patients were obtained from the South Korean nationwide cohort Health Insurance Review and Assessment Service database. This study included 58,831 eligible patients of the total 813,907 patients diagnosed with ESKD between January 1, 2007 and December 31, 2017. Of the 58,831 ESKD patients, 3292 (5.6%) were newly diagnosed with cancer. The average duration between the diagnosis of ESKD and cancer was 3.3 ± 1.9 years (mean ± standard deviation), with no differences between hemodialysis, peritoneal dialysis, and kidney transplant groups. The most commonly observed cancer sites in ESKD patients were the colorectum, lung, and liver. The incidence of cancer increased progressively among patients undergoing kidney transplant, peritoneal dialysis, and hemodialysis in that order. Hemodialysis patients were found to have an increased risk of digestive tract cancer compared with kidney transplant patients (adjusted hazard ratio = 1.9; 95% confidence interval: 1.31-2.81; P < 0.001). The study findings may be a useful reference for cancer-screening guidelines.

Risk of fracture according to glucocorticoid use after renal biopsy: a nationwide population-based study.

Few data are available regarding fracture risk in patients treated with glucocorticoids, including patients with kidney disease. A population-based retrospective cohort study was performed using Health Insurance Review and Assessment Service database, a South Korean nationwide cohort set. This study identified 44,702 patients with diagnosis code of kidney diseases who received a renal biopsy between January 1, 2012 and December 31, 2017. A total of 8,624 patients met all study inclusion criteria. A total of 1,406 fractures of any site were observed in the study period. The glucocorticoid-exposed group had more fractures than the unexposed (14.4% vs 8.8%, P < 0.0001). Vertebral fractures were the most common, followed by upper limb, and lower limb fractures. The exposed group showed a remarkably higher hazard ratio of fracture risk (HR 6.0, 95% CI 5.01-7.23) than the unexposed group, indicating systemic glucocorticoid exposure was highly associated with fracture risk. Although HR increased at doses even less than 5 mg/day, it was independent of dose. Older age showed a significant effect on fracture risk (HR 1.2, 95% CI 1.05-1.44), even after adjusting for systemic glucocorticoid exposure. Glucocorticoids was associated with higher risk of fracture even at a low daily dose and short term exposure.

Optimal cut-off value of high-sensitivity troponin I in diagnosing myocardial infarction in patients with end-stage renal disease.

End-stage renal disease (ESRD) is a major risk factor for cardiovascular disease and the prognosis after myocardial infarction (MI) is dismal. Although cardiac troponin is a key diagnostic test, troponin levels are often elevated in ESRD patients without evidence of MI. Thus, this study attempted to determine the optimal diagnostic value of high-sensitivity troponin I (hsTnI) by dialysis modality in ESRD patients.Medical records of adult dialysis patients who visited tertiary emergency department (ED) were collected retrospectively. Diagnosis of MI was made according to the fourth universal definition of MI. The cut-off values were calculated using a receiver operating characteristic (ROC) curve.Medical records of 1144 patients were analyzed and MI was diagnosed in 82 patients (75 on hemodialysis and 7 on peritoneal dialysis). The optimal cut-off value of hsTnI in hemodialysis patients was 75 ng/L, with 93.33% sensitivity and 60.76% specificity. Area under the curve (AUC) was .870 (95% confidence interval (CI) .833-.906). The optimal cut-off value of hsTnI in peritoneal dialysis patients was 144 ng/L, with 100.00% sensitivity and 83.10% specificity. AUC was .943 (95% CI .893-.992).The dialysis modality should also be considered when diagnosing MI using hsTnI in ESRD patients.