Autophagy caused by oxidative stress promotes TGF-ß1-induced epithelial-to-mesenchymal transition in human peritoneal mesothelial cells.

Epithelial-to-mesenchymal transition (EMT) is one of the main causes of peritoneal fibrosis. However, the pathophysiological mechanisms of EMT, specifically its relationship with autophagy, are still unknown. This study aimed to evaluate the role of autophagy in transforming growth factor-beta 1 (TGF-ß1)-induced EMT in human peritoneal mesothelial cells (HPMCs). Primary cultured HPMCs were treated with TGF-ß1 (2 and 5 ng/mL) and changes in autophagy markers and the relationship between autophagy and EMT were evaluated. We also identified changes in EMT- and autophagy-related signaling pathways after autophagy and NADPH oxidase 4 (NOX4) inhibition. TGF-ß1 increased the generation of NOX4 and reactive oxygen species (ROS) in HPMCs, resulting in mitochondrial damage. Treatment with GKT137831 (20 µM), a NOX1/4 inhibitor, reduced ROS in the mitochondria of HPMC cells and reduced TGF-ß1-induced mitochondrial damage. Additionally, the indirect inhibition of autophagy by GKT137831 (20 µM) downregulated TGF-ß1-induced EMT, whereas direct inhibition of autophagy using 3-methyladenine (3-MA) (2 mM) or autophagy-related gene 5 (ATG5) gene silencing decreased the TGF-ß1-induced EMT in HPMCs. The suppressor of mothers against decapentaplegic 2/3 (Smad2/3), autophagy-related phosphoinositide 3-kinase (PI3K) class III, and protein kinase B (Akt) pathways, and mitogen-activated protein kinase (MAPK) signaling pathways, such as extracellular signal-regulated kinase (ERK) and P38, were involved in TGF-ß1-induced EMT. Autophagy and NOX4 inhibition suppressed the activation of these signaling pathways. Direct inhibition of autophagy and its indirect inhibition through the reduction of mitochondrial damage by upstream NOX4 inhibition reduced EMT in HPMCs. These results suggest that autophagy could serve as a therapeutic target for the prevention of peritoneal fibrosis in patients undergoing peritoneal dialysis.

Dual Immunoglobulin Domain-Containing Cell Adhesion Molecule Increases Early in Renal Tubular Cell Injury and Plays Anti-Inflammatory Role.

Dual immunoglobulin domain-containing cell adhesion molecule (DICAM) is a type I transmembrane protein that presents in various cells including renal tubular cells. This study evaluated the expression and protective role of DICAM in renal tubular cell injury. HK-2 cells were incubated and treated with lipopolysaccharide (LPS, 30 µg/mL) or hydrogen peroxide (H2O2, 100 µM) for 24 h. To investigate the effect of the gene silencing of DICAM, small interfering RNA of DICAM was used. Additionally, to explain its role in cellular response to injury, DICAM was overexpressed using an adenoviral vector. DICAM protein expression levels significantly increased following treatment with LPS or H2O2 in HK-2 cells. In response to oxidative stress, DICAM showed an earlier increase (2-4 h following treatment) than neutrophil gelatinase-associated lipocalin (NGAL) (24 h following treatment). DICAM gene silencing increased the protein expression of inflammation-related markers, including IL-1ß, TNF-α, NOX4, integrin ß1, and integrin ß3, in H2O2-induced HK-2 cell injury. Likewise, in the LPS-induced HK-2 cell injury, DICAM knockdown led to a decrease in occludin levels and an increase in integrin ß3, IL-1ß, and IL-6 levels. Furthermore, DICAM overexpression followed by LPS-induced HK-2 cell injury resulted in an increase in occludin levels and a decrease in integrin ß1, integrin ß3, TNF-α, IL-1ß, and IL-6 levels, suggesting an alleviating effect on inflammatory responses. DICAM was elevated in the early stage of regular tubular cell injury and may protect against renal tubular injury through its anti-inflammatory properties. DICAM has a potential as an early diagnostic marker and therapeutic target for renal cell injury.

Impact of Ring Finger Protein 20 and Its Downstream Regulation on Renal Tubular Injury in a Unilateral Nephrectomy Mouse Model Fed a High-Fat Diet.

Abnormal lipid metabolism increases the relative risk of kidney disease in patients with a single kidney. Using transcriptome analysis, we investigated whether a high-fat diet leads to abnormalities in lipid metabolism and induces kidney cell-specific damage in unilateral nephrectomy mice. Mice with unilateral nephrectomy fed a high-fat diet for 12 weeks exhibited progressive renal dysfunction in proximal tubules, including lipid accumulation, vacuolization, and cell damage. Ring finger protein 20 (RNF20) is a ligase of nuclear receptor corepressor of peroxisome proliferator-activated receptors (PPARs). The transcriptome analysis revealed the involvement of RNF20-related transcriptome changes in PPAR signaling, lipid metabolism, and water transmembrane transporter under a high-fat diet and unilateral nephrectomy. In vitro treatment of proximal tubular cells with palmitic acid induced lipotoxicity by altering RNF20, PPARα, and ATP-binding cassette subfamily A member 1 (ABCA1) expression. PPARγ and aquaporin 2 (AQP2) expression decreased in collecting duct cells, regulating genetic changes in the water reabsorption process. In conclusion, a high-fat diet induces lipid accumulation under unilateral nephrectomy via altering RNF20-mediated regulation and causing functional damage to cells as a result of abnormal lipid metabolism, thereby leading to structural and functional kidney deterioration.

In vivo imaging of renal microvasculature in a murine ischemia-reperfusion injury model using optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) provides three-dimensional structural and semiquantitative imaging of microvasculature in vivo. We developed an OCTA imaging protocol for a murine kidney ischemia-reperfusion injury (IRI) model to investigate the correlation between renal microvascular changes and ischemic damage. Mice were divided into mild and moderate IRI groups according to the duration of ischemia (10 and 35 mins, respectively). Each animal was imaged at baseline; during ischemia; and at 1, 15, 30, 45, and 60 mins after ischemia. Amplitude decorrelation OCTA images were constructed with 1.5-, 3.0-, and 5.8-ms interscan times, to calculate the semiquantitative flow index in the superficial (50-70 µm) and the deep (220-340 µm) capillaries of the renal cortex. The mild IRI group showed no significant flow index change in both the superfial and the deep layers. The moderate IRI group showed a significantly decreased flow index from 15 and 45 mins in the superficial and deep layers, respectively. Seven weeks after IRI induction, the moderate IRI group showed lower kidney function and higher collagen deposition than the mild IRI group. OCTA imaging of the murine IRI model revealed changes in superficial blood flow after ischemic injury. A more pronounced decrease in superficial blood flow than in deep blood flow was associated with sustained dysfunction after IRI. Further investigation on post-IRI renal microvascular response using OCTA may improve our understanding of the relationship between the degree of ischemic insult and kidney function.

Efficiency of a 24-hour on-call system for early recompression therapy for acute decompression sickness.

Background: Early recompression therapy is suggested for a better clinical outcome of decompression sickness (DCS) patients. This study analyzed the efficacy of our 24-hour on-call system for early recompression therapy. Methods: We conducted a single-center retrospective cohort study. They were classified into DCS Type I versus Type II, duty time versus non-duty time groups based on the time of emergency department (ED) admission, and hospitalization versus discharge groups according to clinical outcomes. Baseline characteristics, diving variables, and in-hospital course were analyzed. Results: This study investigated 341 acute DCS patients. A total of 81 and 260 patients had Type I and Type II DCS, respectively. While 198 patients accessed the center during duty time, 143 presented during non-duty time. Fifty patients were admitted, and 291 patients were discharged. Total median time from symptom onset to HBO2 therapy was 259 minutes: 240 minutes for the duty group and 292 minutes for the non-duty group (p=0.16); 251 minutes for the discharged group and 291 minutes for the hospitalized group (p<0.001). The median time from ED admission to HBO2 therapy was 65 minutes: 60 minutes for the duty group and 69 minutes for the non-duty group (p=0.23); 63.4 minutes for the discharged group and 92 minutes for the hospitalized group (p=0.05). Conclusion: The 24-hour on-call system was able to provide acute DCS patients with early recompression therapy even during non-duty time. However, in terms of the outcome of treatment of patients, quicker arrival at the hospital and swifter recompression therapy are needed.

Lymphoscintigraphy in patients with breast cancer-related lymphedema after sentinel lymph node dissection and axillary radiation therapy.

The purpose of this study was to investigate lymphoscintigraphy pattern according to the presence or absence of axillary site radiation therapy (aRTx) in breast cancer-related lymphedema (BCRL) patients who underwent sentinel lymph node dissection (SLND). The participants were patients who visited our facility from July 2014 to June 2021 due to upper extremity edema. Among them, patients who underwent SLND after the diagnosis of breast cancer were included. The participants were divided into a group without aRTx (group A) and a group with aRTx (group B). In each patient's lymphoscintigraphy, axillary lymph node uptake (ALNU), lymphatic flow delay, dermal back flow, and the presence of any collateral pathway were checked. Thirty-three patients were enrolled. In all, 27 patients were classified in Group A, and 6 patients were classified in Group B. Between the 2 groups, we found a significant difference (P value < .05) between groups at ALNU and lymphatic flow delay. However, there was no significant difference between groups at the dermal backflow and the presence of a collateral pathway (P value > .05). And 24.2% of patients who developed lymphedema after SLND showed normal lymphoscintigraphy. In this study we suggest that SLND and aRTx affects the activity of the axillary lymph node and ultimately adversely affects lymphatic flow, becoming a risk factor for lymphedema. In addition, regardless of SLND or aRTx, lymphedema may eventually occur in the patient with normal lymphoscintigraphy.

Paricalcitol Improves Hypoxia-Induced and TGF-ß1-Induced Injury in Kidney Pericytes.

Recently, the role of kidney pericytes in kidney fibrosis has been investigated. This study aims to evaluate the effect of paricalcitol on hypoxia-induced and TGF-ß1-induced injury in kidney pericytes. The primary cultured pericytes were pretreated with paricalcitol (20 ng/mL) for 90 min before inducing injury, and then they were exposed to TGF-ß1 (5 ng/mL) or hypoxia (1% O2 and 5% CO2). TGF-ß1 increased α-SMA and other fibrosis markers but reduced PDGFRß expression in pericytes, whereas paricalcitol reversed the changes. Paricalcitol inhibited the TGF-ß1-induced cell migration of pericytes. Hypoxia increased TGF-ß1, α-SMA and other fibrosis markers but reduced PDGFRß expression in pericyte, whereas paricalcitol reversed them. Hypoxia activated the HIF-1α and downstream molecules including prolyl hydroxylase 3 and glucose transporter-1, whereas paricalcitol attenuated the activation of the HIF-1α-dependent molecules and TGF-ß1/Smad signaling pathways in hypoxic pericytes. The gene silencing of HIF-1α vanished the hypoxia-induced TGF-ß1, α-SMA upregulation, and PDGFRß downregulation. The effect of paricalcitol on the HIF-1α-dependent changes of fibrosis markers was not significant after the gene silencing of HIF-1α. In addition, hypoxia aggravated the oxidative stress in pericytes, whereas paricalcitol reversed the oxidative stress by increasing the antioxidant enzymes in an HIF-1α-independent manner. In conclusion, paricalcitol improved the phenotype changes of pericyte to myofibroblast in TGF-ß1-stimulated pericytes. In addition, paricalcitol improved the expression of fibrosis markers in hypoxia-exposed pericytes both in an HIF-1α-dependent and independent manner.

Single-Dose Toxicity Study on ML171, a Selective NOX1 Inhibitor, in Mice.

BACKGROUND: ML171 is a potent nicotinamide adenine dinucleotide phosphate oxidase (NOX) inhibitor with isoform selectivity only for NOX1. This study is aimed at investigating the safety of ML171 after a single intraperitoneal (IP) injection in mice. METHODS: The toxicity of a single dose of ML171 was evaluated in 6-week-old Institute of Cancer Research (ICR) mice in a good laboratory practice (GLP) laboratory. Twenty-five mice of each sex were assigned to five groups: negative control, vehicle control, and 125, 250, and 500 mg/kg of ML171. All mice were acclimatized for one week before beginning the study. Mice received an IP injection of ML171 or vehicle. The general condition and mortality of the animals were observed. The mice were sacrificed to evaluate histopathology 14 days after the administration of ML171 or vehicle. RESULTS: Bodyweights were not significantly different in any group. Three males and one female died due to ML171 administration in the 500 mg/kg dose group. Autopsies of the surviving mice did not reveal any significant abnormalities after the injection of 125 mg/kg of ML171. However, the anterior lobe edge of the liver was thickened and adhesions between the liver and adjacent organs were observed in mice treated with 250 or 500 mg/kg of ML171. In addition, hypertrophy of centrilobular hepatocytes and inflammatory cell infiltration were observed after injection of 250 and 500 mg/kg of ML171. CONCLUSION: Our results indicate that the lethal IP injection dose of ML171 is 500 mg/kg for both males and females. Mortality were not observed for lower doses of ML171. The safe dose of single IP ML171 in ICR mice was 250 mg/kg or less. Further studies are needed to confirm the safety of ML171 in the human body.

Renoprotective Effects of Alpha-1 Antitrypsin against Tacrolimus-Induced Renal Injury.

The protective effects of alpha-1 antitrypsin (AAT) in tacrolimus (TAC)-induced renal injury was evaluated in a rat model. The TAC group rats were subcutaneously injected with 2 mg/kg TAC every day for four weeks. The TAC with AAT group was cotreated with daily subcutaneous injections of TAC and intraperitoneal injections of AAT (80 mg/kg) for four weeks. The effects of AAT on TAC-induced renal injury were evaluated using serum biochemistry, histopathology, and Western blotting. The TAC injection significantly increased renal interstitial fibrosis, inflammation, and apoptosis as compared to the control treatment. The histopathological examination showed that cotreatment of TAC and AAT attenuated interstitial fibrosis (collagen, fibronectin, and α-SMA staining), and α-SMA expression in Western blotting was also decreased. Immunohistochemical staining for inflammation (osteopontin and ED-1 staining) revealed improved interstitial inflammation in the TAC with AAT group compared to that in the TAC group. The TAC treatment increased renal apoptosis compared to the control treatment, based on the results of increased immunohistochemical staining of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), increased caspase-3 activity, and lower Bcl-2 to Bad expression ratio. However, AAT cotreatment significantly changed these markers and consequently showed decreased apoptosis. AAT protects against TAC-induced renal injury via antifibrotic, anti-inflammatory, and antiapoptotic effects.

The Crucial Role of Xanthine Oxidase in CKD Progression Associated with Hypercholesterolemia.

In the present study, we investigated the effects of xanthine oxidase (XO) inhibition on cholesterol-induced renal dysfunction in chronic kidney disease (CKD) mice, and in low-density lipoprotein (LDL)-treated human kidney proximal tubule epithelial (HK-2) cells. ApoE knockout (KO) mice underwent uninephrectomy to induce CKD, and were fed a normal diet or high-cholesterol (HC) diet along with the XO inhibitor topiroxostat (1 mg/kg/day). HK-2 cells were treated with LDL (200 µg/mL) and topiroxostat (5 µM) or small interfering RNA against xanthine dehydrogenase (siXDH; 20 nM). In uninephrectomized ApoE KO mice, the HC diet increased cholesterol accumulation, oxidative stress, XO activity, and kidney damage, while topiroxostat attenuated the hypercholesterolemia-associated renal dysfunction. The HC diet induced cholesterol accumulation by regulating the expressions of genes involved in cholesterol efflux (Nr1h3 and Abca1) and synthesis (Srebf2 and Hmgcr), which was reversed by topiroxostat. Topiroxostat suppressed the expressions of genes related to hypercholesterolemia-associated inflammation and fibrosis in the unilateral kidney. LDL stimulation evoked changes in the cholesterol metabolism, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and NF-κB pathways in HK-2 cells, which were mitigated by XO inhibition with topiroxostat or siXDH. These findings suggest that XO inhibition exerts renoprotective effects against hypercholesterolemia-associated kidney injury. XO could be a novel therapeutic target for hypercholesterolemia-associated kidney injury in uninephrectomized patients.

NOX1 Inhibition Attenuates Kidney Ischemia-Reperfusion Injury via Inhibition of ROS-Mediated ERK Signaling.

The protective effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) 1 inhibition against kidney ischemia-reperfusion injury (IRI) remain uncertain. The bilateral kidney pedicles of C57BL/6 mice were clamped for 30 min to induce IRI. Madin-Darby Canine Kidney (MDCK) cells were incubated with H2O2 (1.4 mM) for 1 h to induce oxidative stress. ML171, a selective NOX1 inhibitor, and siRNA against NOX1 were treated to inhibit NOX1. NOX expression, oxidative stress, apoptosis assay, and mitogen-activated protein kinase (MAPK) pathway were evaluated. The kidney function deteriorated and the production of reactive oxygen species (ROS), including intracellular H2O2 production, increased due to IRI, whereas IRI-mediated kidney dysfunction and ROS generation were significantly attenuated by ML171. H2O2 evoked the changes in oxidative stress enzymes such as SOD2 and GPX in MDCK cells, which was mitigated by ML171. Treatment with ML171 and transfection with siRNA against NOX1 decreased the upregulation of NOX1 and NOX4 induced by H2O2 in MDCK cells. ML171 decreased caspase-3 activity, the Bcl-2/Bax ratio, and TUNEL-positive tubule cells in IRI mice and H2O2-treated MDCK cells. Among the MAPK pathways, ML171 affected ERK signaling by ERK phosphorylation in kidney tissues and tubular cells. NOX1-selective inhibition attenuated kidney IRI via inhibition of ROS-mediated ERK signaling.

Comparison of the short-term effects of hyperbaric oxygen therapy and complex decongestive therapy on breast cancer-related lymphedema: A pilot study.

Although there have been some reports that hyperbaric oxygen therapy (HBOT) is effective in treating breast cancer-related lymphedema (BCRL), controversy regarding its therapeutic effects remains.We sought to evaluate the efficacy of HBOT in addition to conventional complex decongestive therapy (CDT) for BCRL.A prospective observational study was conducted on 10 patients with BCRL. After screening, the subjects were stratified into a CDT-only group and a CDT and HBOT combination (CDT-HBOT) group. All patients received a total of 10 treatments over 2 weeks. Changes in the circumference of the upper limbs, quality-of-life questionnaire results, and bioelectrical impedance values were compared between the 2 groups.Between both groups, there were no significant differences in demographic or clinical characteristics and in the quality-of-life outcomes for lymphedema of the limbs. The parameters measured by bioimpedance spectroscopy showed more significant improvements in the CDT-HBOT group than in the CDT-only group.In patients with BCRL, HBOT may be recommended as an adjunct treatment to the existing therapies.

Alpha-1 antitrypsin inhibits formaldehyde-induced apoptosis of human peritoneal mesothelial cells.

BACKGROUND: The alpha-1 antitrypsin (AAT) protein has an important role in the anti-inflammatory and apoptotic response. AAT inhibits not only serine proteases but also cysteine and aspartic proteases. Apoptosis results from the sequential activation of cysteine proteases of the caspase family. This study aimed to evaluate the effect of AAT on formaldehyde-induced apoptosis of human peritoneal mesothelial cells (HPMCs). METHODS: HPMCs were cultured and treated with formaldehyde (250 µM) to induce apoptosis. In the AAT group, the cultured HPMCs were pretreated with AAT (2 mg/mL) for 1 h before formaldehyde treatment. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays to determine cell viability, and flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays to detect apoptosis. The MTT assays were used to find optimal concentrations of formaldehyde and AAT. We measured caspase-3 activity and used Western blotting to estimate Bcl-2 and Bad expression. RESULTS: Flow cytometry and TUNEL assays revealed that formaldehyde exposure significantly increased apoptosis compared with the control treatment, but pretreatment with AAT significantly inhibited this effect. Compared with the control, caspase-3 activity was significantly increased and the ratio of Bcl-2 to Bad expression significantly decreased following treatment with formaldehyde. However, caspase-3 activity was significantly lower and the Bcl-2 to Bad expression ratio higher in the AAT group than in the formaldehyde-only group. CONCLUSION: AAT inhibits formaldehyde-induced apoptosis of HPMCs via a caspase-mediated pathway. These data support a potential use for AAT as a therapeutic agent for the inhibition of peritoneal cell apoptosis during peritoneal dialysis.

Successful treatment of decompression sickness complicated with acute hepatic infarction and acute kidney injury: a case report.

Decompression sickness is a disease caused by abrupt pressure change and presents various symptoms. To date, acute kidney injury associated with decompression sickness has been reported frequently, but there is no report of hepatic infarction associated with decompression sickness. We report a case of acute kidney injury and acute hepatic infarction treated with hyperbaric oxygen (HBO2) therapy and dialysis in a patient with severe decompression sickness after work diving.

Association Between Duration of Dysphagia Recovery and Lesion Location on Magnetic Resonance Imaging in Patients With Middle Cerebral Artery Infarction.

OBJECTIVE: To investigate association between lesion location on magnetic resonance imaging (MRI) performed after an infarction and the duration of dysphagia in middle cerebral artery (MCA) infarction. METHODS: A videofluoroscopic swallowing study was performed for 59 patients with dysphagia who were diagnosed as cerebral infarction of the MCA territory confirmed by brain MRI. Lesions were divided into 11 regions of interest: primary somatosensory cortex, primary motor cortex, supplementary motor cortex, anterior cingulate cortex, orbitofrontal cortex, parieto-occipital cortex, insular cortex, posterior limb of the internal capsule (PLIC), thalamus, basal ganglia (caudate nucleus), and basal ganglia (putamen). Recovery time was defined as the period from the first day of L-tube feeding to the day that rice porridge with thickening agent was prescribed. Recovery time and brain lesion patterns were compared and analyzed. RESULTS: The mean recovery time of all patients was 26.71±16.39 days. The mean recovery time was 36.65±15.83 days in patients with PLIC lesions and 32.6±17.27 days in patients with caudate nucleus lesions. Only these two groups showed longer recovery time than the average recovery time for all patients. One-way analysis of variance for recovery time showed significant differences between patients with and without lesions in PLIC and caudate (p<0.001). CONCLUSION: Injury to both PLIC and caudate nucleus is associated with longer recovery time from dysphagia.

The emerging role of xanthine oxidase inhibition for suppression of breast cancer cell migration and metastasis associated with hypercholesterolemia.

Hypercholesterolemia is reported to increase reactive oxygen species (ROS) and to promote breast cancer progression. ROS play an important role in tumor biology, and xanthine oxidase (XO) is an enzyme that generates ROS. The effects of febuxostat (FBX), an XO inhibitor, on breast cancer cell migration under LDL stimulation in vitro and metastasis of breast cancer associated with hypercholesterolemia in vivo were studied. In vitro, FBX significantly inhibited LDL-induced ROS production and cell migration. Treatment of small interfering RNA against XO was consistent with the findings of FBX treatment. In vivo, a significant increase of tumor growth and pulmonary metastasis was observed in a xenograft mouse model with 4T1 cells on a high cholesterol diet (HCD), both of which were markedly inhibited by FBX or allopurinol treatment. Moreover, ERK represented the main target-signaling pathway that was affected by FBX treatment in a xenograft mouse model on an HCD evaluated by NanoString nCounter analysis. Consistently, MEK/ERK inhibitors directly decreased the LDL-induced cell migration in vitro. In conclusion, FBX mitigates breast cancer cell migration and pulmonary metastasis in the hyperlipidemic condition, associated with decreased ROS generation and MAPK phosphorylation. The inhibition of ERK pathways is likely to underlie the XO inhibitor-mediated suppression of breast cancer cell migration.-Oh, S.-H., Choi, S.-Y., Choi, H.-J., Ryu, H.-M., Kim, Y.-J., Jung, H.-Y., Cho, J.-H., Kim, C.-D., Park, S.-H., Kwon, T.-H., Kim, Y.-L. The emerging role of xanthine oxidase inhibition for suppression of breast cancer cell migration and metastasis associated with hypercholesterolemia.

Effects of Different Bandaging Methods for Treating Patients With Breast Cancer-Related Lymphedema.

OBJECTIVE: To compare the treatment effects, satisfaction with the treatment, and performance improvement following bandage treatment using the spiral method and spica method for breast cancer-related lymphedema (BCRL). METHODS: A prospective study with 46 patients with BCRL was conducted. All patients were divided into either the spiral or spica group for non-elastic bandage therapy and received the same treatment for 2 weeks, apart from the group-specific bandaging method used. For both groups, the Quality of Life Instrument score before treatment, changes in the volume of lymphedema limb and the Disability of the Arm, Shoulder, and Hand (DASH) score before and after treatment, and treatment satisfaction after treatment were compared. The Student t-test was used to compare the parameters between the two different bandage methods. RESULTS: With respect to the treatment outcomes, total volume reduction and proximal part volume reduction after treatment were 98.0±158.3 mL and 56.0±65.4 mL in the spiral method group and 199.0±125.1 mL and 106.1±82.2 mL in the spica method group, respectively. Therefore, the spica method group showed a significantly better improvement (p<0.05). The DASH score changes after treatment showed that the spiral group score increased by 3.8±5.4 and the spica group score increased by 7.7±6.1; thus, a significantly better improvement was noted in the spica group (p<0.05). CONCLUSION: The spica method indicated better volume reduction and DASH score improvement than the spiral method. Therefore, the spica method may be more effective for treating patients with BCRL.

Implementation of Targeted Temperature Management in a Patient with Cerebral Arterial Gas Embolism.

Cerebral arterial gas embolism (CAGE) shows various manifestations according to the quantity of gas and the brain areas affected. The symptoms range from minor motor weakness, headache, and confusion to disorientation, convulsions, hemiparesis, unconsciousness, and coma. A 46-year-old man was transferred to our emergency department due to altered sensorium. Immediately after a controlled ascent from 33 m of seawater, he complained of shortness of breath and rigid extremities, lapsing into unconsciousness. He was intubated at another medical center, where a brain computerized axial tomography scan showed no definitive abnormal findings. Pneumothorax and obstructing lesions were apparent in the left thorax of the computed tomography scan. Following closed thoracostomy, we provided hyperbaric oxygen therapy (HBOT) using U.S. Navy Treatment Table (USN TT) 6A. A brain magnetic resonance imaging diffusion image taken after HBOT showed acute infarction in both middle and posterior cerebral arteries. We implemented targeted temperature management (TTM) to prevent worsening of cerebral function in the intensive care unit. After completing TTM, we repeated HBOT using USN TT5 and started rehabilitation therapy. He fully recovered from the neurological deficits. This is the first case of CAGE treated with TTM and consecutive HBOTs suggesting that TTM might facilitate salvage of the penumbra in severe CAGE.

Clinical Importance of Peak Cough Flow in Dysphagia Evaluation of Patients Diagnosed With Ischemic Stroke.

OBJECTIVE: To investigate the relationship between peak cough flow (PCF), pulmonary function tests (PFT), and severity of dysphagia in patients with ischemic stroke. METHODS: This study included patients diagnosed with ischemic stroke, who underwent videofluoroscopic swallowing study (VFSS), PCF and PFT from March 2016 to February 2017. The dysphagia severity was assessed using the videofluoroscopic dysphagia scale (VDS). Correlation analysis of VDS, PFT and PCF was performed. Patients were divided into three groups based on VDS score. One-way ANOVA of VDS was performed to analyze PCF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and age among the different groups. RESULTS: The correlation coefficients of VDS and PCF, VDS and FVC, and VDS and FEV1 were -0.836, -0.508, and -0.430, respectively, all of which were statistically significant at the level of p<0.001. The one-way ANOVA indicated statistically significant differences in PCF, FVC, FEV1, and age among the VDS groups. Statistically significant differences in VDS and age were observed between aspiration pneumoia and non-aspiration pneumonia groups. CONCLUSION: Coughing is a useful factor in evaluating the risk of aspiration in dysphagia patients. Evaluation of respiratory and coughing function should be conducted during the swallowing assessment of patients with ischemic stroke.

The Efficacy of Fentanyl Transdermal Patch as the First-Line Medicine for the Conservative Treatment of Osteoporotic Compression Fracture.

OBJECTIVE: There are no strong guidelines on how long or how we should undertake conservative treatment during the acute period of an osteoporotic vertebral compression fracture (VCF). METHODS: We treated 202 patients with conservative treatment on VCF from March 2012 to August 2015. On inclusion criteria, 75 patients (22 males and 53 females) were included in the final analysis. After admission, a transdermal fentanyl patch with low dose (12.5 µg) application was attempted in all patients. In an unresponsive patient, the fentanyl patch was increased by 25 µg. After identifying the tolerable toilet ambulation of the patient without any assistance, hospital discharge was recommended. We classified two patient groups into one favorable group and one unfavorable group and compared several clinical and radiological factors. RESULTS: Among 75 patients, the clinical outcome of 57 patients (76%) was favorable, but that of 18 patients (24%) was unfavorable. In clinical outcomes, the numeric rating scale at 6 and 12 months and Odom's criteria at 12 months was significantly different between the favorable and the unfavorable groups. The dose of the patches used showed statistically significant differences between the two groups (p=0.001). CONCLUSION: The only statistically significant affecting factor for an unfavorable outcome was the use of a higher dose fentanyl patch. Our data inferred that the unresponsiveness to a low-dose fentanyl patch could be helpful to select patients necessary for percutaneous vertebroplasty or kyphoplasty.