Ultrasonographic diagnosis and surgical outcomes of adnexal masses in children and adolescents.

This study aimed to evaluate the incidence, clinical diagnosis, surgical treatment, and histopathological findings of adnexal masses in children and adolescents. This retrospective study included patients aged < 20 years who were diagnosed with adnexal masses between January 2005 and December 2018 at the Konkuk University Medical Center. Adnexal masses were diagnosed in 406 patients. The mean age of patients was 17.3 years at the time of diagnosis. The primary presenting symptoms and signs were abdominal pain (81.4%), mass per abdomen (13.7%), dysmenorrhea (3.4%), incidental finding (2%), and abdominal distention (0.5%). In total, 204 patients underwent surgery for adnexal masses, and 202 patients were observed without surgery. Histopathological examination revealed 110 benign neoplasms, 72 non-neoplastic lesions, 3 ectopic pregnancies, 3 tubo-ovarian abscesses, 7 borderline malignant tumors, and 9 non-epithelial ovarian malignant tumors. Abdominal pain was the most common reason for hospital visits and surgery in adolescents and young women with adnexal masses. The ultrasonographic diagnosis was consistent with the histopathological diagnosis. In recent years, the use of minimally invasive surgery such as laparoscopy and robotic, has increased in young patients with adnexal masses.

Silicon Carbide Nanostructures as Potential Carbide Material for Electrochemical Supercapacitors: A Review.

Silicon carbide (SiC) is a very promising carbide material with various applications such as electrochemical supercapacitors, photocatalysis, microwave absorption, field-effect transistors, and sensors. Due to its enticing advantages of high thermal stability, outstanding chemical stability, high thermal conductivity, and excellent mechanical behavior, it is used as a potential candidate in various fields such as supercapacitors, water-splitting, photocatalysis, biomedical, sensors, and so on. This review mainly describes the various synthesis techniques of nanostructured SiC (0D, 1D, 2D, and 3D) and its properties. Thereafter, the ongoing research trends in electrochemical supercapacitor electrodes are fully excavated. Finally, the outlook of future research directions, key obstacles, and possible solutions are emphasized.

Hemodialysis with Cohort Isolation to Prevent Secondary Transmission during a COVID-19 Outbreak in Korea.

BACKGROUND: Health care-associated infections during previous coronavirus epidemics involving severe acute respiratory syndrome and Middle East respiratory syndrome resulted from human-to-human transmission in hemodialysis (HD) facilities. The effect of a strategy of HD with cohort isolation-separate dialysis sessions for close contacts of patients with confirmed coronavirus disease 2019 (COVID-19)-on the prevention of secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in HD units is unknown. METHODS: Our multicenter cohort study of an HD with cohort isolation strategy enrolled close contacts of patients with confirmed COVID-19, including patients on HD and health care workers in HD units. Close contacts had been identified by epidemiologic investigation and tested negative on an immediate screening test for SARS-CoV-2. RESULTS: As of March 14, 11 patients on HD and 7 health care workers from 11 HD centers were diagnosed as having COVID-19. The immediate screening test was performed in 306 people, and among them, 302 close contacts with negative test results were enrolled. HD with cohort isolation was performed among all close contacts for a median of 14 days in seven centers. During cohort isolation, nine patients showed symptoms but tested negative for SARS-CoV-2. Two health care workers in the HD units (0.66% of the total group) were diagnosed at the termination test for SARS-CoV-2. CONCLUSIONS: The transmission of COVID-19 can be controlled without closure of HD centers by implementing preemptive activities, including early detection with rapid testing, cohort isolation, collaboration between institutions, and continuous monitoring of infection. Our strategy and experience may provide helpful guidance for circumstances involving the rapid spread of infectious diseases such as COVID-19.

Renal hemosiderosis secondary to intravascular hemolysis after mitral valve repair: A case report.

RATIONALE: Renal hemosiderosis is a disease in which hemosiderin deposits in the renal cortex as a form of iron overload. However, cases of renal hemosiderosis due to intravascular hemolysis following mitral valve repair have been rarely reported. PATIENT CONCERNS: We present the case of a 62-year-old woman who developed asymptomatic urinary abnormalities including microscopic hematuria and proteinuria due to renal hemosiderosis following a mitral valve repair surgery performed two years earlier. DIAGNOSES: A percutaneous renal biopsy showed no specific glomerular abnormality, tubular atrophy, or interstitial fibrosis but extensive deposition of hemosiderin in the proximal tubule. The patient was diagnosed with renal hemosiderosis and chronic intravascular hemolysis following mitral valve repair. INTERVENTIONS: Our patient refused a mitral valve repeat surgery and hence was treated with oral iron preparations, N-acetylcysteine, and a ß-receptor blocker. OUTCOMES: Moderate mitral regurgitation with the regurgitant blood striking against the annuloplasty ring was confirmed on follow-up echocardiography. After the 24-month follow-up period, hemolytic anemia persisted, but there was no significant decline of renal function. LESSONS: For cases of chronic intravascular hemolysis accompanied with asymptomatic urinary abnormalities, a renal biopsy is required to exclude underlying kidney pathology and predict potential renal insufficiency.

Efficacy and Safety of CKD-11101 (Proposed Biosimilar of Darbepoetin-Alfa) Compared with Darbepoetin-Alfa in Patients on Hemodialysis: A Randomized, Double-Blinded, Parallel-Group Phase III Study.

BACKGROUND: Darbepoetin-alfa is an erythropoiesis-stimulating agent (ESA) with a long elimination half-life that achieves better hemoglobin (Hb) stability than short-acting ESAs. OBJECTIVE: We aimed to evaluate the efficacy and safety of intravenous CKD-11101 (a biosimilar of darbepoetin-alfa) compared with those of darbepoetin-alfa in hemodialysis patients. METHODS: The study was performed in 24 centers in Korea between June 2015 and June 2017. The study subjects were randomized in a double-blind manner. The follow-up duration was 24 weeks, which consisted of 20 weeks of maintenance and 4 weeks of evaluation period. All patients underwent a stabilization period to achieve a target baseline Hb of 10-12 g/dL before randomization. Following randomization, patients received darbepoetin-alfa or CKD-11101 weekly or biweekly. RESULTS: A total of 403 patients were randomized into two groups, and a total of 325 patients (80.6%) completed the investigation. The differences between the two groups in terms of change in the average Hb level from baseline to evaluation were not significant. The average administered dose of ESA was similar between the groups. There was no difference in the proportion of patients who maintained the target Hb during the evaluation period [60.4% vs. 66.2% in the CKD-11101 and darbepoetin-alfa groups, respectively (p = 0.3038)]. In addition, the safety analysis, consisting of adverse events and adverse drug reactions, showed comparable results between the two groups. CONCLUSION: The changes in the level of Hb, dose of erythropoietin, and achievement rate of the target Hb during the study period were comparable between the groups. CKD-11101 has an equivalent efficacy and safety compared with darbepoetin-alfa in patients undergoing hemodialysis.

Effect of adjuvant therapy on the risk of recurrence in early-stage leiomyosarcoma: A meta-analysis.

OBJECTIVES: To assess the effect of adjuvant chemotherapy (AC) or radiotherapy (AR) on the risk of recurrence in surgically treated patients with early-stage uterine leiomyosarcoma (uLMS). METHODS: We searched the PubMed, EMBASE, and MEDLINE, and Cochrane databases for publications up to March 2019, which compared patients with early-stage uLMS who received AC or AR with those who did not. The primary endpoint was recurrence rate. Random- or fixed-effects models were used for pooled estimates of the effect of adjuvant treatments on recurrence rates. Subgroup analyses were conducted based on study design, surgical staging, AC regimen (gemcitabine/docetaxel regimen), and type of AR. RESULTS: Three randomized trials and 9 observational studies (9 studies for AC vs. observation, n = 496; 9 studies for AR vs. observation, n = 425) were included. The meta-analysis indicated that AC did not decrease the risk of recurrence compared with observation (odds ratio [OR] = 0.65, 95% confidence interval [CI] = 0.37-1.15, P = 0.14; P = 0.09 and I2 = 42.1). Similarly, AR did not decrease the risk of recurrence compared with observation (OR = 1.11, 95% CI = 0.56-2.21, P = 0.76; P = 0.10 and I2 = 40.4). Meta-regression analyses revealed no significant association between median follow-up time and recurrence. In subgroup analyses (study design, surgical staging, gemcitabine/docetaxel regimen, type of AR), neither AC nor AR decreased the risk of recurrence significantly. CONCLUSION: AC, including gemcitabine/docetaxel regimen, or AR did not reduce the recurrence rate in patients with early-stage uLMS.

A case report on the acute and late complications associated with carbon monoxide poisoning: Acute kidney injury, rhabdomyolysis, and delayed leukoencephalopathy.

RATIONALE: Acute kidney injury (AKI), rhabdomyolysis, and delayed leukoencephalopathy after carbon monoxide (CO) poisoning are very rare. We report a case presenting with AKI, rhabdomyolysis, and delayed leukoencephalopathy after CO poisoning. PATIENT CONCERNS: The patient was admitted to our emergency department due to loss of consciousness after CO exposure during a suicide attempt. DIAGNOSES: Laboratory findings revealed elevated carboxyhemoglobin, serum creatinine, and serum muscle enzyme levels. Initially, this patient was diagnosed with AKI and rhabdomyolysis due to CO poisoning. A month after the CO poisoning, she showed neuropsychiatric symptoms. Brain magnetic resonance imaging showed white-matter hyperintensity on the T2 flair image. Therefore, she was diagnosed with delayed leukoencephalopathy after CO poisoning. INTERVENTIONS: At the same time as diagnosis of AKI and rhabdomyolysis, the normobaric oxygen and hydration therapies were performed. A month later, rehabilitation was started due to delayed leukoencephalopathy. OUTCOMES: Her renal function and muscle enzyme levels were completely restored with alert mental status. She could walk with the aid of a walker at last visit. LESSONS: This case shows that we should consider about rare acute and late complications such as AKI, rhabdomyolysis, and delayed leukoencephalopathy after CO poisoning.

Efficacy and safety of CKD-11101 (darbepoetin-alfa proposed biosimilar) compared with NESP in anaemic chronic kidney disease patients not on dialysis.

OBJECTIVE: To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP® in treatment of anaemia in patients with chronic kidney disease not on dialysis. CLINICAL TRIAL REGISTRATION: NCT03431623. METHOD: In this multi-centre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24 weeks, during which patients were treated every 2 weeks. All patients who completed the EEP were treated with CKD-11101 every 2 weeks for the first 4 weeks and every 4 weeks for the safety evaluation period (SEP), which was from 24 weeks to 52 weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb. RESULTS: The mean Hb level was increased in both groups during the EEP (both p < 0.001). The difference in mean Hb level change between the two groups was 0.01 g/dL (95% CI = -0.213-0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was -1.40 mcg (95% CI = -6.859-4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group). CONCLUSION: CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.

The Quality of Life of Hemodialysis Patients Is Affected Not Only by Medical but also Psychosocial Factors: a Canonical Correlation Study.

BACKGROUND: The quality of life (QoL) of patients with end-stage renal disease (ESRD) is very poor, plausibly due to both psychosocial and medical factors. This study aimed to determine the relationship among psychosocial factors, medical factors, and QoL in patients with ESRD undergoing hemodialysis (HD). METHODS: In total, 55 male and 47 female patients were evaluated (mean age, 57.1 ± 12.0 years). The QoL was evaluated using the Korean version of World Health Organization Quality of Life Scale-Abbreviated Version. The psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, Pittsburgh Sleep Quality Index, and Zarit Burden Interview. The medical factors were assessed using laboratory examinations. Correlation and canonical correlation analyses were performed to investigate the association patterns. RESULTS: The QoL was significantly correlated with the psychosocial factors, and to a lesser extent with the medical factors. The medical and psychosocial factors were also correlated. The canonical correlation analysis indicated a correlation between QoL and psychosocial factors (1st canonical correlation = 0.696, P < 0.001; 2nd canonical correlation = 0.421, P = 0.191), but not medical factors (1st canonical correlation = 0.478, P = 0.475; 2nd canonical correlation = 0.419, P = 0.751). The medical and psychosocial factors were also correlated (1st canonical correlation = 0.689, P < 0.001; 2nd canonical correlation = 0.603, P = 0.009). CONCLUSION: Psychosocial factors influence QoL in patients with ESRD, and should thus be carefully considered when caring for these patients in clinical practice.

Protein kinase C beta II upregulates intercellular adhesion molecule-1 via mitochondrial activation in cultured endothelial cells.

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of PKCßII on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral PKCßII gene transfer and pharmacological inhibitors, the role of PKCßII on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by PKCßi (10 nM), a selective inhibitor of PKCßII. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by PKCßi. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of PKCßII inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of PKCßII using adenoviral PKCßII increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, PKCßII-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that PKCßII plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of PKCßII-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.

Hypersensitivity pneumonitis associated with azathioprine therapy in a patient with granulomatosis with polyangiitis.

Granulomatosis with polyangiitis (GPA), an autoimmune disease characterized by inflammatory granulomas and necrotizing small-vessel vasculitis, primarily affects the respiratory tract and kidneys. Azathioprine (AZA) is a purine analog that is commonly used for maintaining GPA remission after induction therapy with cyclophosphamide. While the dose-dependent side effects of AZA are common and well known, hypersensitivity reactions such as pulmonary toxicity are rare. Here, we describe a case involving a 38-year-old man with GPA-associated pauci-immune crescentic glomerulonephritis who developed subacute hypersensitivity pneumonitis (HP) during AZA maintenance therapy. Five months after the initiation of AZA administration (100 mg/day), the patient was admitted with a 7-day history of cough, dyspnea, and fever. High-resolution computed tomography of the chest showed ill-defined centrilobular nodules and diffuse ground-glass opacities in both lung fields. Bronchoscopy with bronchoalveolar lavage was negative for infectious etiologies. A transbronchial lung biopsy specimen revealed poorly formed non-necrotizing granulomas. A chest radiograph obtained at 2 weeks after discontinuation of AZA showed normal findings. The findings from this case suggest that AZA-induced HP should be considered as a differential diagnosis when a patient with GPA exhibits fresh pulmonary lesions accompanied by respiratory symptoms during AZA therapy.

Secreted APE1/Ref-1 inhibits TNF-α-stimulated endothelial inflammation via thiol-disulfide exchange in TNF receptor.

Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) is a multifunctional protein with redox activity and is proved to be secreted from stimulated cells. The aim of this study was to evaluate the functions of extracellular APE1/Ref-1 with respect to leading anti-inflammatory signaling in TNF-α-stimulated endothelial cells in response to acetylation. Treatment of TNF-α-stimulated endothelial cells with an inhibitor of deacetylase that causes intracellular acetylation, considerably suppressed vascular cell adhesion molecule-1 (VCAM-1). During TSA-mediated acetylation in culture, a time-dependent increase in secreted APE1/Ref-1 was confirmed. The acetyl moiety of acetylated-APE1/Ref-1 was rapidly removed based on the removal kinetics. Additionally, recombinant human (rh) APE1/Ref-1 with reducing activity induced a conformational change in rh TNF-α receptor 1 (TNFR1) by thiol-disulfide exchange. Following treatment with the neutralizing anti-APE1/Ref-1 antibody, inflammatory signals via the binding of TNF-α to TNFR1 were remarkably recovered, leading to up-regulation of reactive oxygen species generation and VCAM-1, in accordance with the activation of p66(shc) and p38 MAPK. These results strongly indicate that anti-inflammatory effects in TNF-α-stimulated endothelial cells by acetylation are tightly linked to secreted APE1/Ref-1, which inhibits TNF-α binding to TNFR1 by reductive conformational change, with suggestion as an endogenous inhibitor of vascular inflammation.

Ulmus davidiana ethanol extract inhibits monocyte adhesion to tumor necrosis factor-alpha-stimulated endothelial cells.

BACKGROUND: Ulmus davidiana var. japonica Rehder (UD) has long been used in traditional folk medicine in Asia. This study is designed to investigate the antiadhesive activity of the ethanol extract of UD (UDE) and its underlying mechanisms in cultured endothelial cells. METHODS: The dried root bark of UD was extracted with 80% (v/v) ethanol. The antiadhesive activity of the UDE was investigated in cultured human umbilical vein endothelial cells and human embryonic kidney epithelial 293T (HEK 293T) cells stably transfected with pGL3-vascular cell adhesion molecule (VCAM)-1-luc. Monocyte adhesion in endothelial cells was induced by tumor necrosis factor-alpha (TNF-α), and the protective effects of UDE on monocyte-endothelial cell adhesion, VCAM-1 expression, reactive oxygen species production, and nuclear factor-κB activity were determined. RESULTS: Exposure to UDE at a concentration of 3-30 µg/mL for 24 hours produced no detectable cytotoxicity in human umbilical vein endothelial cells, but it significantly inhibited TNF-α-induced monocyte adhesion and VCAM-1 expression. TNF-α treatment of HEK 293T/VCAM-1-luc cells resulted in increased luciferase activity of the VCAM-1 promoter, which was inhibited by treatment with UDE. Additionally, TNF-α-induced reactive oxygen species generation, nuclear translocation of nuclear factor-κB, and IκBα degradation in human umbilical vein endothelial cells were effectively reduced by treatment with 30 µg/mL of UDE. CONCLUSION: Our results indicated that UDE treatment inhibited TNF-α-induced monocyte adhesion in endothelial cells, suggesting that UD may reduce vascular endothelial inflammation.

The 18-kDa Translocator Protein Inhibits Vascular Cell Adhesion Molecule-1 Expression via Inhibition of Mitochondrial Reactive Oxygen Species.

Translocator protein 18 kDa (TSPO) is a mitochondrial outer membrane protein and is abundantly expressed in a variety of organ and tissues. To date, the functional role of TSPO on vascular endothelial cell activation has yet to be fully elucidated. In the present study, the phorbol 12-myristate 13-acetate (PMA, 250 nM), an activator of protein kinase C (PKC), was used to induce vascular endothelial activation. Adenoviral TSPO overexpression (10-100 MOI) inhibited PMA-induced vascular cell adhesion molecule-1 (VCAM-1) and intracellular cell adhesion molecule-1 (ICAM-1) expression in a dose dependent manner. PMA-induced VCAM-1 expressions were inhibited by Mito-TEMPO (0.1-0.5 µM), a specific mitochondrial antioxidants, and cyclosporin A (1-5 µM), a mitochondrial permeability transition pore inhibitor, implying on an important role of mitochondrial reactive oxygen species (ROS) on the endothelial activation. Moreover, adenoviral TSPO overexpression inhibited mitochondrial ROS production and manganese superoxide dismutase expression. On contrasts, gene silencing of TSPO with siRNA increased PMA-induced VCAM-1 expression and mitochondrial ROS production. Midazolam (1-50 µM), TSPO ligands, inhibited PMA-induced VCAM-1 and mitochondrial ROS production in endothelial cells. These results suggest that mitochondrial TSPO can inhibit PMA-induced endothelial inflammation via suppression of VCAM-1 and mitochondrial ROS production in endothelial cells.

Trichostatin A Modulates Angiotensin II-induced Vasoconstriction and Blood Pressure Via Inhibition of p66shc Activation.

Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I (AT1R) inhibitor, valsartan (10 µM), but not by the AT2R inhibitor, PD123319. TSA (1~10 µM) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing AT1R. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through AT1R.

Clinical and psychosocial factors predicting health-related quality of life in hemodialysis patients.

Many patients with end-stage renal disease have significant impairment in health-related quality of life (HRQoL). Most previous studies have focused on clinical factors; however, quality of life can also be affected by psychosocial factors. The aim of this study was to identify the possible predictors of HRQoL among clinical and psychosocial factors in hemodialysis (HD) patients. The study included 101 patients who were undergoing HD. Psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, and Pittsburgh Sleep Quality Index. We also assessed laboratory and clinical factors, including albumin, Kt/V as a marker of dialysis adequacy, normalized protein catabolic rate, and duration of HD. The Euro Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D) was used to evaluate HRQoL. The mean EQ-5D index score was 0.704 ± 0.199. The following variables showed a significant association with the EQ-5D index: age (P < 0.001), depression (P < 0.001), anxiety (P < 0.001), support from friends (P < 0.001), cognitive function (P < 0.001), duration of HD (P = 0.034), triglyceride (P = 0.031), total iron-binding capacity (P = 0.036), and phosphorus (P = 0.037). Multiple regression analysis showed that age (95% confidence interval [CI] -0.008 to -0.002), anxiety (95% CI -0.025 to -0.009), and support from friends (95% CI 0.004 to 0.018) were independent predictors of impaired HRQoL. This study explored determinants of impaired HRQoL in HD patients. We found that impaired HRQoL was independently associated with age, anxiety, and support from friends. We should consider psychosocial as well as clinical factors when evaluating ways to improve HRQoL in HD patients.

Cytoplasmic localization and redox cysteine residue of APE1/Ref-1 are associated with its anti-inflammatory activity in cultured endothelial cells.

Apurinic/apyrimidinic endonuclease1/redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in base excision DNA repair and transcriptional regulation of gene expression. APE1/Ref-1 is mainly localized in the nucleus, but cytoplasmic localization has also been reported. However, the functional role of cytoplasmic APE1/Ref-1 and its redox cysteine residue are still unknown. We investigated the role of cytoplasmic APE1/Ref-1 on tumor necrosis factor-α (TNF-α)-induced vascular cell adhesion molecule-1 (VCAM-1) expressions in endothelial cells. Endogenous APE1/Ref-1 was mainly observed in the nucleus, however, cytoplasmic APE1/Ref-1 was increased by TNF-α. Cytoplasmic APE1/Ref-1 expression was not blunted by cycloheximide, a protein synthesis inhibitor, suggesting cytoplasmic translocation of APE1/Ref-1. Transfection of an N-terminus deletion mutant APE1/Ref-1(29-318) inhibited TNF-α-induced VCAM-1 expression, indicating an anti-inflammatory role for APE1/Ref-1 in the cytoplasm. In contrast, redox mutant of APE1/Ref-1 (C65A/C93A) transfection led to increased TNF-α-induced VCAM-1 expression. Our findings suggest cytoplasmic APE1/Ref-1 localization and redox cysteine residues of APE1/Ref-1 are associated with its anti-inflammatory activity in endothelial cells.

Severe lactic acidosis and acute pancreatitis associated with cimetidine in a patient with type 2 diabetes mellitus taking metformin.

An 82-year-old woman with type 2 diabetes mellitus, hypertension, and unstable angina presented with severe lactic acidosis and acute kidney injury (AKI) accompanied by acute pancreatitis. Her medical history revealed that she had taken cimetidine for two weeks while taking other medications, including metformin. Continuous veno-venous hemodiafiltration (CVVHDF) was initiated under diagnosis of lactic acidosis due to metformin and AKI caused by cimetidine-induced acute pancreatitis. In three days of CVVHDF, the levels of serum biochemical markers of lactic acidosis and AKI improved and the patient's urine output reached over 1 L/day. The pancreatitis improved over time.

Proangiogenic TIE2(+)/CD31 (+) macrophages are the predominant population of tumor-associated macrophages infiltrating metastatic lymph nodes.

Tumor-associated macrophages (TAMs) accumulate in various cancers and promote tumor angiogenesis and metastasis, and thus may be ideal targets for the clinical diagnosis of tumor metastasis with high specificity. However, there are few specific markers to distinguish between TAMs and normal or inflammatory macrophages. Here, we show that TAMs localize in green fluorescent protein-labeled tumors of metastatic lymph nodes (MLNs) from B16F1 melanoma cells but not in necrotic tumor regions, suggesting that TAMs may promote the growth of tumor cells and the progression of tumor metastasis. Furthermore, we isolated pure populations of TAMs from MLNs and characterized their gene expression signatures compared to peritoneal macrophages (PMs), and found that TAMs significantly overexpress immunosuppressive cytokines such as IL-4, IL-10, and TGF-ß as well as proangiogenic factors such as VEGF, TIE2, and CD31. Notably, immunological analysis revealed that TIE2(+)/CD31(+) macrophages constitute the predominant population of TAMs that infiltrate MLNs, distinct from tissue or inflammatory macrophages. Importantly, these TIE2(+)/CD31(+) macrophages also heavily infiltrated MLNs from human breast cancer biopsies but not reactive hyperplastic LNs. Thus, TIE2(+)/ CD31(+) macrophages may be a unique histopathological biomarker for detecting metastasis in clinical diagnosis, and a novel and promising target for TAM-specific cancer therapy.

Kienböck's disease associated with radiocephalic fistula formation in a patient with end-stage renal disease.

Kienböck's disease, which consists of osteonecrosis and collapse of the lunate bone, causes chronic pain and dysfunction of the wrist. Patients on hemodialysis are occasionally present with wrist pain, but Kienböck's disease is rarely reported in dialysis patients. This case study describes Kienböck's disease in a patient with end-stage renal disease on hemodialysis. A 39-year-old male with a 1-year history of hemodialysis presented with left wrist pain that increased progressively over 6 months. The patient had no history of trauma or any other risk factors known to be associated with Kienböck's disease. Physical examination of the wrist at the site of the arteriovenous fistula showed swelling and tenderness with decreased range of motion. Radiographic examination showed articular collapse and fracture of the body of lunate consistent with stage IIIb Kienböck's disease. An intercarpal arthrodesis with autogenous bone graft was performed.