Bile pigment, bilirubin, and biliverdin concentrations may change as a results of biliary tract cancer (BTC) altering the mechanisms of radical oxidation and heme breakdown. We explored whether changes in bile pigment components could help distinguish BTC from benign biliary illness by evaluating alterations in patients with BTC. We collected bile fluid from 15 patients with a common bile duct stone (CBD group) and 63 individuals with BTC (BTC group). We examined the bile fluid’s bilirubin, biliverdin reductase (BVR), heme oxygenase (HO-1), and bacterial taxonomic abundance. Serum bilirubin levels had no impact on the amounts of bile HO-1, BVR, or bilirubin. In comparison to the control group, the BTC group had considerably higher amounts of HO-1, BVR, and bilirubin in the bile. The areas under the curve for the receiver operating characteristic curve analyses of the BVR and HO-1 were 0.832 (p<0.001) and 0.891 (p<0.001), respectively. Firmicutes was the most prevalent phylum in both CBD and BTC, according to a taxonomic abundance analysis, however the Firmicutes/Bacteroidetes ratio was substantially greater in the BTC group than in the CBD group. The findings of this study showed that, regardless of the existence of obstructive jaundice, biliary carcinogenesis impacts heme degradation and bile pigmentation, and that the bile pigment components HO-1, BVR, and bilirubin in bile fluid have a diagnostic significance in BTC. In tissue biopsies for the diagnosis of BTC, particularly for distinguishing BTC from benign biliary strictures, bile pigment components can be used as additional biomarkers.

Purpose: : This study aims to investigate the status of delirium intervention in adult intensive care unit (ICU) patients and the perception of this delirium by medical staff. Methods: : This retrospective study involves 185 patients, whereas, a descriptive survey is conducted with 197 medical staff members. Results: : The delirium group includes 100 patients (54.1%). The incidence of delirium is 64.9% in the medical ICU, 65.9% in the surgical ICU, 42.4% in the neuro ICU, and 46.5% in the cardiac ICU. The percentages of delirium prevention intervention differs between the two groups: 65.0% in the delirium group and 95.3% in the non-delirium group. The medical staff recognize that delirium is a common problem in the ICU (100.0%) and requires active medical intervention (98.5%). Conclusion : The length of stay at the ICU is longer in the delirium group than in the non-delirium group. It is necessary to standardize delirium prevention and treatment protocols to be equally applicable to all ICU patients.

Background/Aims: Cigarette smoking is an important modifiable risk factor in kidney disease progression. However, the underlying mechanisms for this are lacking. This study aimed to assess whether nicotine (NIC), a major toxic component of cigarette smoking, would exacerbates tacrolimus (TAC)-induced renal injury. Methods: Sprague-Dawley rats were treated daily with NIC, TAC, or both drugs for 4 weeks. The influence of NIC on TAC-caused renal injury was examined via renal function, histopathology, oxidative stress, mitochondria, endoplasmic reticulum (ER) stress, and programmed cell death (apoptosis and autophagy). Results: Both NIC and TAC significantly impaired renal function and histopathology, while combined NIC and TAC treatment aggravated these parameters beyond the effects of either alone. Increased oxidative stress, ER stress, mitochondrial dysfunction, proinf lammatory and profibrotic cytokine expressions, and programmed cell death from either NIC or TAC were also aggravated by the two combined. Conclusions Our observations suggest that NIC exacerbates chronic TAC nephrotoxicity, implying that smoking cessation may be beneficial for transplant smokers taking TAC.

Thrombotic microangiopathy (TMA) is defined by specific clinical characteristics, including microangiopathic hemolytic anemia, thrombocytopenia, and pathologic evidence of endothelial cell damage, as well as the resulting ischemic end-organ injuries. A variety of clinical scenarios have features of TMA, including infection, pregnancy, malignancy, autoimmune disease, and medications. These overlapping manifestations hamper differential diagnosis of the underlying pathogenesis, despite recent advances in understanding the mechanisms of several types of TMA syndrome. Atypical hemolytic uremic syndrome (aHUS) is caused by a genetic or acquired defect in regulation of the alternative complement pathway. It is important to consider the possibility of aHUS in all patients who exhibit TMA with triggering conditions because of the incomplete genetic penetrance of aHUS. Therapeutic strategies for aHUS are based on functional restoration of the complement system. Eculizumab, a monoclonal antibody against the terminal complement component 5 inhibitor, yields good outcomes that include prevention of organ damage and premature death. However, there remain unresolved challenges in terms of treatment duration, cost, and infectious complications. A consensus regarding diagnosis and management of TMA syndrome would enhance understanding of the disease and enable treatment decision-making.

BACKGROUND: The clinical outcomes and safety of thoracic epidural catheterization in anesthetized adult patients has not yet been established. The purpose of this study was to compare clinical differences between epidural catheterization performed before and after anesthesia for postoperative pain control. METHODS: The medical records of 549 patients who received thoracic epidural catheterization before (awake group, n = 303) or after (anesthetized group, n = 246) induction of anesthesia for major abdominal surgery were reviewed retrospectively. RESULTS: The catheter insertion time (1.6 ± 1.5 vs. 1.1 ± 1.2 min; 95% confidence interval [95% CI], 0.3–0.8; effect size, 0.368; P < 0.001) and number of attempts required for successful epidural catheterization (1 [1, 3] vs. 1 [1, 2], P = 0.003) were increased in the awake group. The incidence rates of dural puncture, vascular injury and postoperative paresthesia were similar between the two groups. The median surgical site numerical rating scale pain score (0 = no pain, 10 = worst pain imaginable) was lower in the awake group than in the anesthetized group (3 vs. 4 on postoperative day 1, P < 0.001; and 2 vs. 3 on postoperative day 3, P = 0.002). Serious complications, including meningitis, epidural abscess, epidural hematoma, spinal cord injury, and paraplegia, were not observed in either group. CONCLUSIONS: Successful epidural catheterization before induction of anesthesia required more attempts versus after anesthesia. Overall complication rates of thoracic epidural catheterization were similar regardless of the timing of the procedure.
Adult ; Analgesia, Epidural ; Anesthesia ; Catheterization* ; Catheters* ; Epidural Abscess ; Hematoma, Epidural, Spinal ; Humans ; Incidence ; Medical Records ; Meningitis ; Pain, Postoperative ; Paraplegia ; Paresthesia ; Postoperative Complications ; Punctures ; Retrospective Studies* ; Vascular System Injuries

PURPOSE: Temsirolimus is effective in the treatment for metastatic non-clear cell renal cell carcinoma (nccRCC) with poor prognosis. We aim to investigate the efficacy and tolerability of temsirolimus in treatment of naïve Asian patients with metastatic/recurrent nccRCC. MATERIALS AND METHODS: From January 2008 to July 2017, data of treatment-naïve, metastatic/recurrent nccRCC patients, who were treated with temsirolimus according to the standard protocol, were collected. The primary end-point was progression-free survival (PFS). Secondary end points were overall survival (OS), objective response rate (ORR), and tolerability of temsirolimus. RESULTS: Forty-four metastatic/recurrent nccRCC patients, 10 from prospective and 34 from retrospective groups, were enrolled; 24 patients (54%) were papillary type, and other histology subtypes included 11 chromophobes (25%), two collecting ducts (5%), one Xp11.2 translocation (2%), and six others (14%). The median PFS and OS were 7.6 months and 17.6 months, res-pectively. ORR was 11% and disease control rate was 83%. Patients with prior nephrectomy had longer PFS (hazard ratio [HR], 0.16; 95% confidence interval [CI], 0.06 to 0.42; p < 0.001) and OS (HR, 0.15; 95% CI, 0.05 to 0.45; p < 0.001). Compared to favorable/intermediate prognosis group, poor prognosis group had shorter median PFS (4.7 months vs. 7.6 months [HR, 2.91; 95% CI, 1.39 to 6.12; p=0.005]) and median OS (9.2 months vs. 17.6 months [HR, 2.84; 95% CI, 1.23 to 6.56; p=0.015]). CONCLUSION: Temsirolimus not only benefits poor-risk nccRCC patients, but it is also effective in favorable or intermediate-risk group in Asians. Temsirolimus was well-tolerated with manageable adverse events.
Asian Continental Ancestry Group ; Carcinoma, Renal Cell ; Disease-Free Survival ; Humans ; Nephrectomy ; Prognosis ; Prospective Studies ; Retrospective Studies

BACKGROUND: Endovascular management of wide-necked aneurysms often requires assisted-techniques with adjunctive devices. Wide-necked aneurysm can be defined with a dome-to-neck ratio or aspect ratio; however, clinical definitions of wide-necked aneurysms vary. This study aimed to determine the most useful definition of wide-necked aneurysm to predict the need for an adjunctive device.METHODS: Among 552 cases of aneurysms, 343 (62.1%) and 209 (37.9%) cases of unruptured and ruptured aneurysms, respectively, were treated in a single institution. For each aneurysm, the (1) dome-to-neck ratio, (2) aspect ratio, and (3) K-ratio (defined as [dome height+maximum dome width]/[2×maximum neck width]) were measured. We statistically analyzed patient data to determine which of the three ratios was most predictive of the need for adjunctive devices.RESULTS: Among 552 cases of aneurysms, 277 (50.2%) and 275 (49.8%) cases were treated with and without adjunctive techniques, respectively. The mean dome-to-neck ratio, aspect ratio, and K-ratio were 1.17±0.39, 1.58±0.61, and 1.37±0.47, respectively. The K-ratio was the strongest predictor of the use of adjunctive devices (P<0.001), and 1.3 was the most appropriate K-ratio cut-off value (sensitivity, 72.9%; specificity, 63.6%).CONCLUSIONS: K-ratio was the most useful predictor of the need for adjunctive devices in the treatment of endovascular aneurysms. These results suggest that the K-ratio may be used to define wide-necked aneurysms requiring complicated management via adjunctive devices.
Aneurysm ; Aneurysm, Ruptured ; Humans ; Intracranial Aneurysm ; Neck ; Sensitivity and Specificity

BACKGROUND/AIMS: Evidence suggests that Shen-Kang (SK), a traditional Chinese herbal medicine, protects against various types of renal injury. In this study, we evaluated whether SK treatment confers renoprotection in a rat model of chronic tacrolimus (TAC) nephropathy. METHODS: Rats were treated daily with TAC (1.5mg/kg, subcutaneously) and SK (450 mg/kg, intravenously) for 4 weeks. The effects of SK on TAC-induced renal injury were assessed by measuring renal function, urine albumin excretion, histopathology, inflammatory cell infiltration, expression of profibrotic (transforming growth factor β1 [TGF-β1] and TGF-β inducible gene-h3 [βig-h3]) and proinflammatory cytokines, oxidative stress, and apoptotic cell death. RESULTS: Administration of SK preserved glomerular integrity (fractional mesangial area and Wilms tumor 1-positive glomeruli), attenuated tubulointerstitial fibrosis, and reduced the number of ectodermal dysplasia 1-positive cells, and this was paralleled by improved urine albumin excretion and renal dysfunction. At the molecular level, SK treatment suppressed expression of TGF-β1/Smad2/3, βig-h3, and proinflammatory cytokines. Oxidative stress and apoptotic cell death were significantly decreased with SK treatment, and apoptosis-related genes were regulated toward cell survival (active caspase-3 and the B-cell lymphoma-2/Bcl2-associated X [Bcl-2/Bax] ratio). CONCLUSIONS SK protects against TAC-induced renal injury.

PURPOSE: Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. MATERIALS AND METHODS: Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. RESULTS: In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). CONCLUSION: Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.
Aspartate Aminotransferases ; Biliary Tract Neoplasms ; Biliary Tract* ; Bilirubin ; Carcinoembryonic Antigen ; Drug Therapy* ; Humans ; Leukocytes ; Methods ; Propensity Score* ; Retrospective Studies ; Sample Size ; Survival Analysis

Retinal pigment epithelium (RPE) is a major component of the eye. This highly specialized cell type facilitates maintenance of the visual system. Because RPE loss induces an irreversible visual impairment, RPE generation techniques have recently been investigated as a potential therapeutic approach to RPE degeneration. The microRNA-based technique is a new strategy for producing RPE cells from adult stem cell sources. Previously, we identified that antisense microRNA-410 (anti-miR-410) induces RPE differentiation from amniotic epithelial stem cells. In this study, we investigated RPE differentiation from umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) via anti-miR-410 treatment. We identified miR-410 as a RPE-relevant microRNA in UCB-MSCs from among 21 putative human RPE-depleted microRNAs. Inhibition of miR-410 induces overexpression of immature and mature RPE-specific factors, including MITF, LRAT, RPE65, Bestrophin, and EMMPRIN. The RPE-induced cells were able to phagocytize microbeads. Results of our microRNA-based strategy demonstrated proof-of-principle for RPE differentiation in UCB-MSCs by using anti-miR-410 treatment without the use of additional factors or exogenous transduction.
Adult Stem Cells ; Antigens, CD147 ; Humans ; Mesenchymal Stromal Cells* ; MicroRNAs ; Microspheres ; Retinal Pigment Epithelium* ; Retinaldehyde* ; Stem Cells ; Umbilical Cord* ; Vision Disorders