Objectives: . FDXR encodes mitochondrial ferredoxin reductase, which is associated with auditory neuropathy spectrum disorder (ANSD) and optic atrophy. To date, only two studies have described FDXR-related hearing loss. The auditory rehabilitation outcomes of this disease entity have not been investigated, and the pathophysiological mechanisms remain incompletely understood. Here we report a hearing-impaired individual with co-segregation of the FDXR variant and post-synaptic type ANSD, who underwent cochlear implantation (CI) with favorable outcomes. We suggest a possible pathophysiological mechanism of adult-onset ANSD involving mitochondrial dysfunction. Methods: . A 35-year-old woman was ascertained to have ANSD. Exome sequencing identified the genetic cause of hearing loss, and a functional study measuring mitochondrial activity was performed to provide molecular evidence of pathophysiology. Expression of FDXR in the mouse cochlea was evaluated by immunohistochemistry. Intraoperatively, electrically evoked compound action potential (ECAP) responses were measured, and the mapping parameters were adjusted accordingly. Audiological outcomes were monitored for over 1 year. Results: . In lymphoblastoid cell lines (LCLs) carrying a novel FDXR variant, decreased ATP levels, reduced mitochondrial membrane potential, and increased reactive oxygen species levels were observed compared to control LCLs. These dysfunctions were restored by administering mitochondria isolated from umbilical cord mesenchymal stem cells, confirming the pathogenic potential of this variant via mitochondrial dysfunction. Partial ECAP responses during CI and FDXR expression in the mouse cochlea indicate that FDXR-related ANSD is post-synaptic. As a result of increasing the pulse width during mapping, the patient’s CI outcomes showed significant improvement over 1-year post-CI. Conclusion . A novel FDXR variant associated with mitochondrial dysfunction and post-synaptic ANSD was first identified in a Korean individual. Additionally, 1-year post-CI outcomes were reported for the first time in the literature. Excellent audiologic results were obtained, and our results reiterate the correlation between genotype and CI outcomes in ANSD.

Nasal cavity and paranasal sinus cancers comprise about 1% of all malignancies, and 5% of head and neck malignancy. Squamous cell carcinoma comprises more than half of nasal cavity cancers. Treatment is determined by considering tumor size, location, staging, age, general condition, purpose of treatment, etc. Conventional therapy includes surgery, radiotherapy, and chemotherapy; however, for the locally advanced, recurrent, or metastatic cancer after conventional therapy, immunotherapy or targeted therapy are taken into consideration. Target therapy attacks specific cancer cells directly, such as cancer cells with certain gene mutation, whereas immunotherapy attacks cancer cells indirectly, stimulating our own immune system, such as T-cell activity. Histologically poorly differentiated carcinomas are treated with surgery, radiotherapy, and sometimes chemotherapy, but 5-year survival rate is low due to frequent recurrence. Here, we present a case of successful targeted therapy applied to recurrent nasal cavity cancer after serial application of conventional therapies.

Background: Corrective osteotomy is an effective surgery for correcting posture in patients with ankylosing spondylitis (AS). Despite satisfactory correction, some patients experience re-stooping during follow-up. However, there have been no studies on restooping in AS. We aimed to analyze the factors that affect re-stooping. Methods: Fifty patients (50 cases) who underwent thoracolumbar corrective osteotomy for AS from March 2006 to April 2018 were analyzed. We defined re-stooping as global kyphosis that recurs after corrective osteotomy. The patients were divided into two groups based on the ratio of correction loss: non-re-stooping group (N group) and re-stooping group (R group). We analyzed the demographic data and radiological parameters, such as modified Stoke Ankylosing Spondylitis Spine Score (mSASSS), sagittal vertical axis, and various angles. We also investigated the factors affecting re-stooping by analyzing the correlation between the ratio of correction loss and various factors. Results: A significant difference was seen in the change in the mSASSS from before surgery to the last follow-up between the N group (2.87 ± 3.08) and the R group (9.20 ± 5.44). In multivariate analysis, only the change in the mSASSS from before surgery to the last follow-up was significantly correlated with the ratio of correction loss. Conclusions Thoracolumbar corrective osteotomy seems to provide high satisfaction among patients with AS but can lead to re-stooping during follow-up. The change in mSASSS was related with re-stooping in the current study. We recommend active rehabilitative exercises and appropriate medication depending on the patient’s condition, which may help delay the postoperative progression of AS.

Background: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meatassociated colon carcinogenesis is not well understood. Objectives: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. Methods: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. Results: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression.Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. Conclusions We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

Sarcopenia is a prevalent complication in patients with chronic kidney disease and is associated with poor quality of life, morbidity, and mortality. Several candidate biomarkers have been evaluated for this condition. This study assessed the serum cystatin C to creatinine (serum cystatin C/Cr) ratio as a potential biomarker for sarcopenia in patients with non-dialysis-dependent chronic kidney disease. Methods: This study enrolled 517 outpatients. Muscle mass (lean tissue index) was measured using a bioimpedance spectroscopic device, and muscle strength (handgrip strength) was also measured. Sarcopenia was defined as a combination of low muscle strength and low muscle mass. Results: Sarcopenia was observed in 25.5% of patients, and the mean serum cystatin C/Cr ratio was significantly higher in patients with sarcopenia than in those without it (1.14 ± 0.26 vs. 1.01 ± 0.27, p < 0.001). The prevalence of sarcopenia and low lean tissue index increased as the cystatin C/Cr ratio increased. The negative predictive value of the cystatin C/Cr ratio for sarcopenia or low lean tissue index was ≥80%. Multivariate analyses revealed that when the serum cystatin C/Cr ratio increased by 1, the risk of sarcopenia, low lean tissue index, and low handgrip strength increased by 4.6-, 7.2-, and 2.6-fold, respectively (p = 0.003, p < 0.001, and p = 0.048). The association was maximized in patients with an estimated glomerular filtration rate of <30 mL/min/1.73 m2. Conclusion: Calculating the serum cystatin C/Cr ratio could be helpful for detecting and managing sarcopenia in patients with chronic kidney disease.

Background: Anti-heparin/platelet factor 4 (PF4) antibodies may trigger severe thrombotic complications in hemodialysis (HD) patients. Tetrameric PF4 has a high affinity for extracellular DNA, which is a key component of neutrophil extracellular traps (NETs); therefore, the interactions between anti-heparin/PF4 antibodies and NETs can contribute to prothrombotic events. This prospective observational study included both incident and maintenance HD (MHD) patients. Methods: Anti-heparin/PF4 antibody levels were measured by enzyme-linked immunosorbent assay; an optical density > 1.8 was regarded as clinically significant. In incident HD patients, we additionally measured serum nucleosome levels as representative markers of NETs, and the contributions of anti-heparin/PF4 and increased serum nucleosome levels to the primary functional patency loss of vascular access was assessed. Results: The frequency of anti-heparin/PF4 antibodies was significantly higher in incident HD patients compared to MHD patients (23.6% vs. 7.7%). Serum nucleosome levels, as well as the white blood cell counts, neutrophil counts, and high-sensitivity C-reactive protein levels, were significantly higher in anti-heparin/PF4 antibody-positive patients compared to the control. Platelet counts tended to be lower in the patients with anti-heparin/PF4 of >1.8 than in the controls. Relative risk calculations showed that the presence of anti-heparin/PF4 antibodies increased the risk of primary functional patency failure by 4.28-fold, and this risk increased further with higher nucleosome levels. Furthermore, in the anti-heparin/PF4 antibody-positive group, the time to first vascular intervention was much shorter, and the risk of repeated intervention was higher, compared to the controls. Conclusion In incident HD patients, the presence of anti-heparin/PF4 antibodies was associated with increased NET formation; this could be a strong predictor of vascular access complications.

Purpose: Dose reduction of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in patients with atrial fibrillation (AF) with renal impairment. This study investigated anticoagulation patterns and outcomes in patients with chronic kidney disease (CKD). Materials and methods: In a prospective observational registry (CODE-AF), 3445 patients with non-valvular AF including 1129 with CKD (estimated glomerular filtration rate ≤ 60 mL min−1 1.73 m−2) were identified between June 1, 2016, and July 3, 2017. Results: Compared with patients with no-CKD, patients with CKD more frequently had a high stroke risk (94.9% vs. 67.0%, p < 0.001) and higher NOAC usage rate (61.1% vs. 47.8%, p < 0.001). Among 718 patients with renal indication for dose reduction (RIDR), 7.5% were potentially overdosed. Among 2587 patients with no-RIDR, 79% were potentially underdosed. Compared with patients with no-RIDR, the underdose rates of dabigatran (0% vs. 88.6%, p = 0.001) and rivaroxaban (0% vs. 79.5%, p = 0.001) were lower in patients with RIDR. However, the underdose rate of apixaban was not different (62.5% vs. 53.9%, p = 0.089). The overdose rate of dabigatran (7.5% vs. 0%) and rivaroxaban (13.7% vs. 0%) was higher in RIDR than in no-RIDR patients. Stroke/transient ischemic attack was significantly higher in CKD patients (1.4 vs. 0.6 per 100 person-years, p = 0.045). Aspirin significantly increased minor bleeding in CKD patients compared with controls (p = 0.037). Conclusion CKD patients might have a high stroke risk and NOAC usage rate. The underdose rate of NOACs decreased in CKD patients, except for apixaban. Aspirin significantly increased minor bleeding in CKD patients.

BACKGROUND: Elevated serum alkaline phosphatase (AP) and γ-glutamyl transferase (γ-GT) are commonly observed in patients with acute pyelonephritis. The goal of this study was to examine the clinical significance of elevated serum AP and γ-GT levels and to explore the mechanisms underlying these changes. METHODS: We examined serum AP and γ-GT levels in 438 patients with acute pyelonephritis. Urine AP/creatinine (Cr), urine γ-GT/Cr, fractional excretion of AP, and fractional excretion of γ-GT (FE(γ-GT)) were evaluated in patients with elevated and normal serum levels. AP isoenzymes were also examined. RESULTS: We identified 77 patients (17.6%) with elevated serum AP and 134 patients (30.6%) with elevated serum γ-GT. Among them, both enzymes were elevated in 64 patients (14.6%). Older age, longer hospital stay, elevated baseline serum Cr, and complicated pyelonephritis were associated with increases in serum AP and γ-GT. Multivariate analysis showed that high serum AP levels were significantly correlated with renal impairment (odds ratio, 2.13; 95% confidence interval, 1.08–4.19; P = 0.029). FE(γ-GT) was significantly lower in patients with elevated serum enzyme levels. The liver fraction for AP isoenzyme profile did not increase in patients with elevated serum AP. CONCLUSION: Our results demonstrated that elevated serum AP and γ-GT levels are associated with complicated pyelonephritis and renal impairment. Lower FE(γ-GT) levels in patients with elevated serum enzymes may be the result of decreased urinary excretion of these enzymes.
Alkaline Phosphatase ; gamma-Glutamyltransferase ; Humans ; Isoenzymes ; Length of Stay ; Liver ; Multivariate Analysis ; Pyelonephritis ; Transferases

BACKGROUND: Controversies exist whether arteriovenous fistula (AVF) placement is preferred over arteriovenous graft (AVG) for elderly patients. Current guidelines did not offer specific recommendations. Thus, this study was conducted to analyze the all-cause mortality and primary patency associated with various vascular access (VA) types according to age group. METHODS: This retrospective observational study investigated the Korean insurance claims data of chronic kidney disease patients who began hemodialysis between January 2008 and December 2016. We investigated all-cause mortality associated with initial VA in incident hemodialysis patients and primary patency between AVF and AVG according to age group. RESULTS: The proportion of patients with a tunneled dialysis catheter (TDC) that was first placed for VA increased from 18.4% in 2008 to 52.3% in 2016. Incident hemodialysis patients with a TDC or AVG for the initial VA had significantly higher mortality risk than patients with an AVF, except for patients over 85 years, who showed no significant difference in all-cause mortality regardless of VA type. In the patency analysis on initial AV access, AVG had significantly poorer primary patency than AVF in all age groups. CONCLUSION: AVF had better patency than AVG in all age groups; however, the benefit of AVF attenuated in the older age groups. The mortality rate between AVF and AVG was not significantly different in patients over 85 years. Therefore, a “patient-first” approach should be emphasized over a “fistula-first” approach in AV access creation for incident hemodialysis patients older than 85 years.
Administrative Claims, Healthcare ; Aged ; Arteriovenous Fistula ; Catheters ; Dialysis ; Humans ; Insurance ; Mortality ; National Health Programs ; Observational Study ; Renal Dialysis ; Renal Insufficiency, Chronic ; Retrospective Studies ; Transplants

BACKGROUND/AIMS: A high body mass index (BMI) is known to correlate with better survival in patients on hemodialysis (HD). However, the impacts of body composition and sarcopenia on survival have not been well studied in this population. METHODS: One hundred and forty-two prevalent HD patients were recruited and followed prospectively for up to 4.5 years. Low muscle mass (measured using a portable, whole-body, bioimpedance spectroscopic device) was defined as a lean tissue index (LTI) two standard deviations (SD) or more below the normal gender-specific mean for young people. Low muscle strength was a handgrip strength (HGS) of less than 30 kg in males and less than 20 kg in females. Sarcopenia was considered present when both LTI and HGS were reduced. RESULTS: The mean age was 59.8 ± 13.1 years; 57.0% were male and 47.2% had diabetes. Forty-seven patients (33.1%) had sarcopenia. During follow-up, 28 patients (19.7%) died, and low LTI (adjusted hazard ratio [HR], 2.77; 95% confidence interval [CI], 1.10 to 6.97) and low HGS (HR 5.65; 95% CI, 1.99 to 16.04) were independently associated with mortality. Sarcopenia was a significant predictor for death (HR, 6.99; 95% CI, 1.84 to 26.58; p = 0.004) and cardiovascular events (HR, 4.33; 95% CI, 1.51 to 12.43; p = 0.006). CONCLUSIONS Sarcopenia was strongly associated with long-term mortality and cardiovascular events in HD patients. Assessment of muscle strength and muscle mass may provide additional prognostic information to survival in patients with end-stage renal disease.