Upregulation of NADH/NADPH oxidase 4 by angiotensin II induces podocyte apoptosis

Angiotensin II induces glomerular and podocyte injury via systemic and local vasoconstrictive or non-hemodynamic effects including oxidative stress. The release of reactive oxygen species (ROS) from podocytes may participate in the development of glomerular injury and proteinuria. We studied the role of oxidative stress in angiotensin II-induced podocyte apoptosis. Methods: Mouse podocytes were incubated in media containing various concentrations of angiotensin II at different incubation times and were transfected with NADH/NADPH oxidase 4 (Nox4) or angiotensin II type 1 receptor for 24 hours. The changes in intracellular and mitochondrial ROS production and podocyte apoptosis were measured according to the presence of angiotensin II. Results: Angiotensin II increased the generation of mitochondrial superoxide anions and ROS levels but suppressed superoxide dismutase activity in a dose- and time-dependent manner that was reversed by probucol, an antioxidant. Angiotensin II increased Nox4 protein and expression by a transcriptional mechanism that was also reversed by probucol. In addition, the suppression of Nox4 by small interfering RNA (siRNA) reduced the oxidative stress induced by angiotensin II. Angiotensin II treatment also upregulated AT1R protein. Furthermore, angiotensin II promoted podocyte apoptosis, which was reduced significantly by probucol and Nox4 siRNA and also recovered by angiotensin II type 1 receptor siRNA. Conclusion: Our findings suggest that angiotensin II increases the generation of mitochondrial superoxide anions and ROS levels via the upregulation of Nox4 and angiotensin II type 1 receptor. This can be prevented by Nox4 inhibition and/or antagonizing angiotensin II type 1 receptor as well as use of antioxidants.

The Childbirth Experience and Life Satisfaction among Women with Disabilities

Purpose@#The aim of this study was to show the association between the childbirth experience and life satisfaction among women with disabilities and estimate the moderating effect of family strengths and social support. @*Methods@#The target sample included disabled married women aged 20-49 years. We used the Disability and Life Dynamics Panel 2018. The total number of participants was 220. Three groups were defined based on the childbirth experience: women who had never given birth (13.6%), those who gave birth before the onset of disability (73.2%), and those who gave birth after the onset of disability (13.2%). We identified differences in general characteristics, family strengths, social support, and life satisfaction across the 3 groups and examined the moderating effect of family strengths and social support for the childbirth experience and life satisfaction. @*Results@#Women who gave birth after the onset of disability were in better health, exhibiting longer disability retention periods. The multiple regression analysis revealed that among women who gave birth after the onset of disability, life satisfaction was significantly higher than that of women without the childbirth experience because of the moderating effect of family strengths. However, social support had no significant effect on the childbirth experience and life satisfaction. @*Conclusion@#We empirically analyzed the status of childbirth before and after the onset of disability using representative survey data. The findings indicate a positive moderating effect of family strengths on the level of life satisfaction among women with disabilities.

Comparison of laxative effects of fermented soybeans (Cheonggukjang) containing toxins and biogenic amines against loperamide-induced constipation mouse model

BACKGROUND/OBJECTIVES@#(Cheonggukjang) is a traditional fermented soybean paste with significant health-promoting effects. On the other hand, there have been insufficient studies on the safety and efficacy of (Cheonggukjang), which is produced using traditional methods containing toxins and biogenic amines (BAs). This study compared the laxative effect of (Cheonggukjang), containing high or low levels of toxins and BAs (HTBC or LTBC) in a loperamide (Lop)-induced constipation mouse model.MATERIALS/METHODS: To induce constipation, Lop (5 mg/kg) was administered orally to ICR mice twice a day for 4 days, and the dose was increased to 8 mg/kg after a 3-day rest period. (Cheonggukjang) (500 mg/kg, HTBC, or LTBC respectively) was administered for four weeks before the Lop treatment. @*RESULTS@#The number of stools, fecal weight, water contents, gastrointestinal transit, and histological alterations were recovered significantly in the HTBC or LTBC groups. HTBC and LTBC administration did not induce significant changes in body weight, dietary intake, and behavior. The opioid-receptor downstream signaling pathway in colon tissues was also evaluated. The c-Kit, stem cell kinase, and mitogen-activated protein kinases subfamilies, including extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinases, and p38, were all downregulated in the HTBC or LTBC-administered mice colon compared to the Lop group. @*CONCLUSION@#These results show that (Cheonggukjang), containing high levels of toxins and BAs, have a similar laxative effect in a mouse model of Lop-induced constipation.

A Comparative Study on the Nursing Dependency of Suspected COVID-19 Patients and General Patients in the Emergency Department / 임상간호연구

Purpose@#This study was conducted to investigate the nursing needs and workload of nurses according to nursing dependency for effective placement of nursing staff in the emergency department (ED). @*Methods@#In June 2020, 256 adult patients who visited the ED were classified as two groups, suspected COVID-19 patients and general patients. The participants’electronic medical records were analyzed using descriptive statistics, t-test, x 2 -test, and Fisher's exact test using the SPSS. @*Results@#The patient dependence score showed a significant difference between the two groups, with an average of 13.99±1.85 for the suspected COVID-19 patient group and 10.58±2.10 for the general patient group (t=12.42, p<.001). There were statistically significant differences in communication (t=3.28, p=.001), mobility (t=3.29, p=.001), nutrition, elimination, and personal care (t=7.34, p<.001) among the six domains of nursing dependency. In the domains of environment, safety, health, and social needs, the dependency score was 3 for all suspected COVID-19 patients and 1 for all general patients. @*Conclusion@#The results of this study confirmed that infection control activities of emergency patients who need isolation affect the patients’ nursing dependency on nursing care.

Autophagy inhibition by cudraxanthone D regulates epithelial–mesenchymal transition in SCC25 cells

Cudraxanthone D (CD) is a natural xanthone compound derived from the root barks of Cudrania tricuspidata . However, the biological functions of CD in human metabolism have been rarely reported until now. Autophagy is the self-degradation process related to cancer cell metastasis. Here, we elucidated the effects of CD on human oral squamous cell carcinoma (OSCC) cells’ metastatic ability. We confirmed that CD effectively decreased the proliferation and viability of SCC25 human OSCC cells in time- and dose-dependent manners. Also, the metastasis phenotype of the SCC25 cell (migration, invasion, and epithelial–mesenchymal transition [EMT]) was inhibited by CD. To further investigate the mechanism by which CD inhibited the metastatic capacity, we detected the relationship between EMT and autophagy in the SCC25 cells. The results revealed that CD inhibited the metastasis of the SCC25 cells by attenuating autophagy. Thus, our findings produced a potential novel agent for the treatment of human OSCC metastasis.

A Comparative Study on the Nursing Dependency of Suspected COVID-19 Patients and General Patients in the Emergency Department / 임상간호연구

Purpose@#This study was conducted to investigate the nursing needs and workload of nurses according to nursing dependency for effective placement of nursing staff in the emergency department (ED). @*Methods@#In June 2020, 256 adult patients who visited the ED were classified as two groups, suspected COVID-19 patients and general patients. The participants’electronic medical records were analyzed using descriptive statistics, t-test, x 2 -test, and Fisher's exact test using the SPSS. @*Results@#The patient dependence score showed a significant difference between the two groups, with an average of 13.99±1.85 for the suspected COVID-19 patient group and 10.58±2.10 for the general patient group (t=12.42, p<.001). There were statistically significant differences in communication (t=3.28, p=.001), mobility (t=3.29, p=.001), nutrition, elimination, and personal care (t=7.34, p<.001) among the six domains of nursing dependency. In the domains of environment, safety, health, and social needs, the dependency score was 3 for all suspected COVID-19 patients and 1 for all general patients. @*Conclusion@#The results of this study confirmed that infection control activities of emergency patients who need isolation affect the patients’ nursing dependency on nursing care.

Autophagy inhibition by cudraxanthone D regulates epithelial–mesenchymal transition in SCC25 cells

Cudraxanthone D (CD) is a natural xanthone compound derived from the root barks of Cudrania tricuspidata . However, the biological functions of CD in human metabolism have been rarely reported until now. Autophagy is the self-degradation process related to cancer cell metastasis. Here, we elucidated the effects of CD on human oral squamous cell carcinoma (OSCC) cells’ metastatic ability. We confirmed that CD effectively decreased the proliferation and viability of SCC25 human OSCC cells in time- and dose-dependent manners. Also, the metastasis phenotype of the SCC25 cell (migration, invasion, and epithelial–mesenchymal transition [EMT]) was inhibited by CD. To further investigate the mechanism by which CD inhibited the metastatic capacity, we detected the relationship between EMT and autophagy in the SCC25 cells. The results revealed that CD inhibited the metastasis of the SCC25 cells by attenuating autophagy. Thus, our findings produced a potential novel agent for the treatment of human OSCC metastasis.

Semantic Network Analysis of Iussues Related to Mental Illness in Korea Media: Focusing on the Five Major Media from 2016 to 2018 / 신경정신의학

OBJECTIVES: This study examined the trend of press reports on mental illness in Korea to help set a desirable direction for future press reports on the subject.METHODS: This study adopted the method of semantic network analysis to analyze the trend of press reporting on mental illness in Korea. The study analyzed 1253 newspaper articles from 2016 to 2018 published by the five major Korean press: The Kyunghyang Shinmun, The Dong-A Ilbo, The Chosun Ilbo, The JoongAng Ilbo, and The Hankyoreh.RESULTS: The number of articles on mental illness is on the decline year by year, with 465 articles in 2016, 406 in 2017, and 382 in 2018. According to keyword analysis, the order of the words of the highest frequency is as follows: treatment (659), patients (486), mental health (466), incidents (436), and children and adolescents (413). In terms of the Degree Centrality, Closeness Centrality, and Betweenness Centrality, the following words are commonly ranked within the top 10 on the lists: treatment, children and adolescents, patient, mental health, depressive disorder, family, suicide, and counselling.CONCLUSION: The press should pay more attention to mental illness, and its reporting should guarantee accuracy, objectivity, fairness, diversity, and social responsibility. In addition, reports on mental illness need to provide balanced health information, considering the readers, from basic information on mental illness to detailed treatment methods. Establishing reporting guidelines for mental illness would help reduce harm and prejudice related to mental illness and increase access to treatment.

Quantitative analysis of proteins related to chemoresistance to paclitaxel and carboplatin in human SiHa cervical cancer cells via iTRAQ / 부인종양

Objective@#This study aimed to identify proteins related to paclitaxel and carboplatin chemoresistance in cervical cancer. @*Methods@#Quantitative proteomic analysis was performed on normal SiHa cells and those treated with paclitaxel and carboplatin for 14 days, with isobaric tags for relative and absolute quantitation (iTRAQ) analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to identify related processes and differentially expressed proteins. @*Results@#A total of 67 and 96 differentially expressed proteins were identified in the paclitaxel- and carboplatin- treated groups, respectively. GO and KEGG enrichment analyses identified 53 (43 upregulated and 10 downregulated) and 85 differentially expressed proteins (70 upregulated and 15 downregulated) in the paclitaxel- and carboplatin-treated groups, respectively. The cell counting kit-8 results revealed that APOA1 was overexpressed in both the paclitaxel- and carboplatin- resistant SiHa cells compared with the control cells. Immunohistochemistry showed that APOA1 was highly expressed in the paclitaxel- and carboplatin- resistant squamous cell carcinoma of the cervix. @*Conclusion@#This study is the first to use iTRAQ to identify paclitaxel- and carboplatin- resistance proteins in cervical cells. We identified several proteins previously unassociated with paclitaxel and carboplatin resistance in cervical cancer, thereby expanding our understanding of paclitaxel and carboplatin resistance mechanisms. Moreover, these findings indicate that the APOA1 protein could serve as a potential marker for monitoring and predicting paclitaxel and carboplatin resistance levels.

Piperlongumine suppressed osteoclastogenesis in RAW264.7 macrophages

Piperlongumine (PL) is a natural product found in long pepper (Piper longum). The pharmacological effects of PL are well known, and it has been used for pain, hepatoprotection, and asthma in Oriental medicine. No studies have examined the effects of PL on bone tissue or bone-related diseases, including osteoporosis. The current study investigated for the first time the inhibitory effects of PL on osteoclast differentiation, bone resorption, and osteoclastogenesis-related factors in RAW264.7 macrophages stimulated by the receptor activator for nuclear factor-κB ligand (RANKL). Cytotoxicity was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and osteoclast differentiation and bone resorption were confirmed by tartrate-resistant acid phosphatase (TRAP) staining and pit formation analysis. Osteoclast differentiation factors were confirmed by western blotting. PL exhibited toxicity in RAW264.7 macrophages, inhibiting osteoclast formation and bone resorption, in addition to inhibiting the expression of osteoclastogenesis-related factors, such as tumor necrosis factor receptor-associated factor 6 (TRAF6), c-Fos, and NFATc1, in RANKL-stimulated RAW264.7 macrophages. These findings suggest that PL is suitable for the treatment of osteoporosis, and it serves as a potential therapeutic agent for various bone diseases.

Comparison of Attention-Deficit/Hyperactivity Disorder Practice in Adults According to a Training Background in Child Psychiatry

OBJECTIVES: Awareness of attention-deficit/hyperactivity disorder (ADHD) in adults has significantly increased; however, clinical data specific to the Korean population are insufficient. Clinical experience of ADHD may differ based on whether psychiatrists have received pediatric psychiatry-specific training. In order to prepare a practice parameter for adult ADHD patients in Korea, we examined questionnaire data to observe how pediatric psychiatry training could affect clinical practice for adults with ADHD. METHODS: A questionnaire about the diagnosis and treatment process was distributed to both general psychiatrists (GPsy) and child and adolescent psychiatrists (CAP) at the summer and winter workshop meetings of Korean Academy of Child and Adolescent Psychiatry. RESULTS: In total, 142 psychiatrists participated in the survey (86 GPsy, 56 CAP). GPsy and CAP preferred pharmacotherapy (GPsy 82.40%, CAP 64.30%) as the primary treatment option and answered that the clinical psychiatric interview is the most necessary step in diagnostic assessment (GPsy 22.16%, CAP 19.00%). The GPsy responded with an optimal and average treatment duration that was shorter than that reported by CAP. CONCLUSION: Identification of the initial presenting symptom as the correct diagnosis and the optimal duration of pharmacotherapy differed between GPsy and CAP in practice, whereas concepts in diagnosis and treatment of ADHD in adults were similar for both groups. These results suggest the urgent need for the Continuing Medical Education program for psychiatrists treating adults with ADHD.

Transduced Tat-aldose Reductase Protects Hippocampal Neuronal Cells against Oxidative Stress-induced Damage

Aldose reductase (AR) protein, a member of the NADPH-dependent aldo-keto reductase family, reduces a wide range of aldehydes and enhances cell survival by inhibition of oxidative stress. Oxidative stress is known as one of the major pathological factor in ischemia. Since the precise function of AR protein in ischemic injury is fully unclear, we examined the function of AR protein in hippocampal neuronal (HT-22) cells and in an animal model of ischemia in this study. Cell permeable Tat-AR protein was produced by fusion of protein transduction domain in Tat for delivery into the cells. Tat-AR protein transduced into HT-22 cells and significantly inhibited cell death and regulated the mitogen-activate protein kinases (MAPKs), Bcl-2, Bax, and Caspase-3 under oxidative stress condition. In an ischemic animal model, Tat-AR protein transduced into the brain tissues through the blood-brain barrier (BBB) and drastically decreased neuronal cell death in hippocampal CA1 region. These results indicate that transduced Tat-AR protein has protective effects against oxidative stress-induced neuronal cell death in vitro and in vivo, suggesting that Tat-AR protein could be used as potential therapeutic agent in ischemic injury.

Influence of Caring Burden and the Way of Coping on Burnout in Caregivers of Cancer Patients / 한국직업건강간호학회지

PURPOSE@#The aims of this study were to identify the effects of caring burden and the way of coping on burnout in caregivers of cancer patients.@*METHODS@#One-hundred and forty family caregivers of cancer patients who visited the cancer center at one tertiary hospital in metropolitan city B were included. The data collection was conducted from August 1st to October 1st, 2018, using a structured, self-reported questionnaire. The collected data were analyzed using descriptive statistics, t-test, one-way ANOVA, Pearson correlation coefficients, and multiple regression.@*RESULTS@#In the multiple regression analysis, the subject's gender (β=.12, p=.028) and caring burden (β=.74, p<.001) had a significant effect on burnout. The explanatory power of the subject's gender, education level, religion, caring time, number of family caregivers, monthly income, economic burden, expectation for treatment, caring burden, the way of aggressive coping, and the way of passive coping with burnout was 63.8% (F=23.28, p<.001).@*CONCLUSION@#Reducing the caring burden in family caregivers of cancer patients will ultimately contribute to reducing burnout, thereby contributing to an improvement in the psychological well-being and quality of life of family members, as well as positively contributing to the recovery of patients.

Influence of Caring Burden and the Way of Coping on Burnout in Caregivers of Cancer Patients / 산업간호학회지

PURPOSE: The aims of this study were to identify the effects of caring burden and the way of coping on burnout in caregivers of cancer patients. METHODS: One-hundred and forty family caregivers of cancer patients who visited the cancer center at one tertiary hospital in metropolitan city B were included. The data collection was conducted from August 1st to October 1st, 2018, using a structured, self-reported questionnaire. The collected data were analyzed using descriptive statistics, t-test, one-way ANOVA, Pearson correlation coefficients, and multiple regression. RESULTS: In the multiple regression analysis, the subject's gender (β=.12, p=.028) and caring burden (β=.74, p<.001) had a significant effect on burnout. The explanatory power of the subject's gender, education level, religion, caring time, number of family caregivers, monthly income, economic burden, expectation for treatment, caring burden, the way of aggressive coping, and the way of passive coping with burnout was 63.8% (F=23.28, p<.001). CONCLUSION: Reducing the caring burden in family caregivers of cancer patients will ultimately contribute to reducing burnout, thereby contributing to an improvement in the psychological well-being and quality of life of family members, as well as positively contributing to the recovery of patients.

Luteolin Induces Apoptosis via Mitochondrial Pathway and Inhibits Invasion and Migration of Oral Squamous Cell Carcinoma by Suppressing Epithelial-Mesenchymal Transition Induced Transcription Factors

Oral squamous cell carcinoma (OSCC) is the most common type of oral malignancy. Numerous therapies have been proposed for its cure. Research is continually being conducted to develop new forms of treatment as current therapies are associated with numerous side-effects. Luteolin, a common dietary flavonoid, has been demonstrated to possess strong anti-cancer activity against various human cancer cell lines. Nevertheless, research into luteolin-based anticancer activity against oral cancer remains scarce. Thus, the objective of this study was to assess the effect of luteolin as an anti-cancer agent. After treatment with luteolin, Ca9-22 and CAL-27 oral cancer cells showed condensed nuclei and enhanced apoptotic rate with evidence of mitochondria-mediated apoptosis. Epithelialmesenchymal transition (EMT) is closely related to tumor migration and invasion. Luteolin suppressed cancer cell invasion and migration in the current study. Elevated expression of E-cadherin, an adherens junction protein, was evident in both cell lines after luteolin treatment. Luteolin also significantly inhibited transcription factors (i.e., N-cadherin, Slug, Snail, Twist, and ZEB-1) that regulated expression of tumor suppressors such as E-cadherin based on Western blot analysis and quantitative PCR. Thus, luteolin could induce mitochondrial apoptosis and inhibit cancer cell invasion and migration by suppressing EMT-induced transcription factors.

Interleukin-13 Increases Podocyte Apoptosis in Cultured Human Podocytes

PURPOSE: Podocytes are important architectures that maintain the crucial roles of glomerular filtration barrier functions. Despite this structural importance, however, the mechanisms of the changes in podocytes that can be an important pathogenesis of minimal change nephrotic syndrome (MCNS) are not clear yet. The aim of this study was to investigate whether apoptosis is induced by interleukin (IL)-13 in cultured human podocytes. METHODS: Human podocytes were treated with different IL-13 doses and apoptotic cells were analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL assay) and fluorescence-activated cell sorting (FACS). RESULTS: The IL-13 increased the number of TUNEL-positive cells in a dose-dependent manner at 6 and 18 hours (P<0.05 and P<0.05, respectively). The apoptosis rate was appeared to be increased slightly in the IL-13-stimulated podocytes (8.63%, 13.02%, and 14.46%; 3, 10 and 30 ng/mL, respectively) than in the control cells (7.66%) at 12 hours by FACS assay. CONCLUSION: Our study revealed that IL-13 expression may increase podocyte apoptosis. Blocking the IL-13 signal pathway can potentially play an important role in regulating the apoptosis of podocytes.

Comparison of Dietary Behaviors and Blood Clinical Indices in Underweight, Normal Weight, Normal Weight Obese and Obese Female College Students / 대한지역사회영양학회지

OBJECTIVES: Normal weight obesity (NWO) is defined as excessive body fat in the context of a normal body mass index (BMI). This condition carries a greater risk of developing noncommunicable chronic disease and has been associated with early inflammation. This study was conducted to compare the anthropometric measurements, eating behaviors, and blood clinical indices among four groups: underweight, normal, normal weight obesity and obesity. METHODS: The subjects included 215 female college students. A questionnaire was administered regarding general characteristics, dietary behaviors, food consumption frequency. Anthropometric measurements and blood clinical indices were also investigated. RESULTS: The average BMI, body fat percentage, waist circumference, fat-free mass, and muscle mass were highest in the obesity group (p < 0.05). Most subjects had tried to lose weight and perceived that their health was worse than before they became college students. The ratio of students in the NWO group who thought their health was very poor was significantly higher than in the other three groups (p < 0.05). The obesity and NWO groups seemed to eat more and their eating speed was significantly faster than the other groups (pv0.001). The consumption frequency of caffeinated beverages was significantly higher in the NWO group than in the other three groups (p < 0.01). WBC was significantly higher in the obesity group (p < 0.05). Serum levels of TG and total cholesterol were also significantly higher in the obesity group (p < 0.05). Serum GPT was significantly higher in the obesity group (p < 0.05) while BUN level was highest in the NWO group (p < 0.05). CONCLUSIONS: The obesity group showed the most health problems while the NWO group seemed relatively healthy. However, NWO can lead to problems such as metabolic syndrome and cardiovascular disease in later life if poor dietary habits are maintained. Therefore, education in appropriate eating habits is needed for these subjects.

Comparison of Dietary Behaviors and Blood Clinical Indices in Underweight, Normal Weight, Normal Weight Obese and Obese Female College Students / 대한지역사회영양학회지

OBJECTIVES: Normal weight obesity (NWO) is defined as excessive body fat in the context of a normal body mass index (BMI). This condition carries a greater risk of developing noncommunicable chronic disease and has been associated with early inflammation. This study was conducted to compare the anthropometric measurements, eating behaviors, and blood clinical indices among four groups: underweight, normal, normal weight obesity and obesity. METHODS: The subjects included 215 female college students. A questionnaire was administered regarding general characteristics, dietary behaviors, food consumption frequency. Anthropometric measurements and blood clinical indices were also investigated. RESULTS: The average BMI, body fat percentage, waist circumference, fat-free mass, and muscle mass were highest in the obesity group (p < 0.05). Most subjects had tried to lose weight and perceived that their health was worse than before they became college students. The ratio of students in the NWO group who thought their health was very poor was significantly higher than in the other three groups (p < 0.05). The obesity and NWO groups seemed to eat more and their eating speed was significantly faster than the other groups (pv0.001). The consumption frequency of caffeinated beverages was significantly higher in the NWO group than in the other three groups (p < 0.01). WBC was significantly higher in the obesity group (p < 0.05). Serum levels of TG and total cholesterol were also significantly higher in the obesity group (p < 0.05). Serum GPT was significantly higher in the obesity group (p < 0.05) while BUN level was highest in the NWO group (p < 0.05). CONCLUSIONS: The obesity group showed the most health problems while the NWO group seemed relatively healthy. However, NWO can lead to problems such as metabolic syndrome and cardiovascular disease in later life if poor dietary habits are maintained. Therefore, education in appropriate eating habits is needed for these subjects.

Low serum bilirubin level predicts the development of chronic kidney disease in patients with type 2 diabetes mellitus

BACKGROUND/AIMS: We evaluated whether serum bilirubin levels can predict the development of chronic kidney disease (CKD) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a retrospective observational longitudinal study of patients presenting at the Pusan National University Hospital. A total of 349 patients with T2DM and preserved kidney function (estimated glomerular filtration rate ≥ 60 mL/min/1.73 m²) were enrolled. The main outcome was the development of CKD stage 3 or greater. The patients were divided into four groups according to the quartiles of the total serum bilirubin levels at baseline. RESULTS: The group with the lowest range of total serum bilirubin level (Q1) showed the highest cumulative incidence of CKD stage 3 or greater than that of the other lower quartiles (Q1 vs. Q4; hazard ratio [HR], 6.75; 95% confidence interval [CI], 1.54 to 29.47; p = 0.011). In multivariate analysis, the risk of developing CKD stage 3 or greater was higher in the second lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q2 vs. Q4; HR, 9.36; 95% CI, 1.33 to 65.73; p = 0.024). In the normoalbuminuria subgroup (n = 236), multivariate analysis showed that the risk of developing CKD stage 3 or greater was higher in the lowest quartile of the serum bilirubin level than that in the highest quartile of the serum bilirubin level (Q1 vs. Q4; HR, 7.36; 95% CI, 1.24 to 35.82; p = 0.019). CONCLUSIONS: Serum bilirubin might be an early clinical marker for predicting the progression of CKD in patients with T2DM and preserved renal function.

Risk Factors of and Treatments for Pharyngocutaneous Fistula Occurring after Oropharynx and Hypopharynx Reconstruction

BACKGROUND: A pharyngocutaneous fistula is a common and difficult-to-manage complication after head and neck reconstruction. It can lead to serious complications such as flap failure, carotid artery rupture, and pharyngeal stricture, and may require additional surgery. Previous radiotherapy, a low serum albumin level, and a higher T stage have been proposed as contributing factors. We aimed to clarify the risk factors for pharyngocutaneous fistula in patients who underwent flap reconstruction and to describe our experiences in treating pharyngocutaneous fistula. METHODS: Squamous cell carcinoma cases that underwent flap reconstruction after cancer resection from 1995 to 2013 were analyzed retrospectively. We investigated several significant clinical risk factors. The treatment modality was selected according to the size of the fistula and the state of the surrounding tissue, with options including conservative management, direct closure, flap surgery, and pharyngostoma formation. RESULTS: A total of 127 cases (18 with fistulae) were analyzed. A higher T stage (P=0.048) and tube-type reconstruction (P=0.007) increased fistula incidence; other factors did not show statistical significance (P>0.05). Two cases were treated with conservative management, 1 case with direct closure, 4 cases with immediate reconstruction using a pectoralis major musculocutaneous flap, and 11 cases with direct closure (4 cases) or additional flap surgery (7 cases) after pharyngostoma formation. CONCLUSIONS: Pharyngocutaneous fistula requires global management from prevention to treatment. In cases of advanced-stage cancer and tube-type reconstruction, a more cautious approach should be employed. Once it occurs, an accurate diagnosis of the fistula and a thorough assessment of the surrounding tissue are necessary, and aggressive treatment should be implemented in order to ensure satisfactory long-term results.