Characteristics Associated with Survival in Patients Receiving Continuous Deep Sedation in a Hospice Care Unit / 한국호스피스완화의료학회지

Continuous deep sedation (CDS) is an extreme form of palliative sedation to relieve refractory symptoms at the end of life. In this study, we shared our experiences with CDS and examined the clinical characteristics associated with survival in patients with terminal cancer who received CDS. We conducted a chart audit of 106 consecutive patients with terminal cancer who received CDS at a single hospice care unit between January 2014 and December 2016. Survival was defined as the first day of admission to the date of death. The associations between clinical characteristics and survival were presented as hazard ratios and 95% confidence intervals using a Cox proportional hazard model. The mean age of participants was 65.2 years, and 33.0% (n=35) were women. Diazepam was the most commonly administered drug, and haloperidol or lorazepam were also used if needed. One sedative was enough for a majority of the patients. Stepwise multivariate analysis identified poor functioning, a high Palliative Prognostic Index score, hyperbilirubinemia, high serum ferritin levels, and a low number of sedatives as independent poor prognostic factors. Our experiences and findings are expected to be helpful for shared decision-making and further research on palliative sedation.

Clinical Practice Guideline for Care in the Last Days of Life / 한국호스피스완화의료학회지

A clinical practice guideline for patients in the dying process in general wards and their families, developed through an evidence-based process, is presented herein. The purpose of this guideline is to enable a peaceful death based on an understanding of suitable management of patients’ physical and mental symptoms, psychological support, appropriate deci-sion-making, family care, and clearly-defined team roles. Although there are limits to the available evidence regarding medical issues in patients facing death, the final recommendations were determined from expert advice and feedback, considering values and preferences related to medical treatment, benefits and harms, and applicability in the real world. This guideline should be applied in a way that takes into account specific health care environments, including the resources of medical staff and differences in the available resources of each institution. This guideline can be used by all medical institutions in South Korea.

LJ-2698, an Adenosine A3 Receptor Antagonist, Alleviates Elastase-Induced Pulmonary Emphysema in Mice

Emphysema, a major component of chronic obstructive pulmonary disease (COPD), is a leading cause of human death worldwide. The progressive deterioration of lung function that occurs in the disease is caused by chronic inflammation of the airway and destruction of the lung parenchyma. Despite the main impact of inflammation on the pathogenesis of emphysema, current therapeutic regimens mainly offer symptomatic relief and preservation of lung function with little therapeutic impact. In the present study, we aimed to discover novel therapeutics that suppress the pathogenesis of emphysema. Here, we show that LJ-2698, a novel and highly selective antagonist of the adenosine A3 receptor, a G protein-coupled receptor involved in various inflammatory diseases, significantly reversed the elastase-induced destructive changes in murine lungs. We found that LJ-2698 significantly prevented elastase-induced airspace enlargement, resulting in restoration of pulmonary function without causing any obvious changes in body weight in mice. LJ-2698 was found to inhibit matrix metalloproteinase activity and pulmonary cell apoptosis in the murine lung. LJ-2698 treatment induced increases in anti-inflammatory cytokines in macrophages at doses that displayed no significant cytotoxicity in normal cell lines derived from various organs. Treatment with LJ-2698 significantly increased the number of anti-inflammatory M2 macrophages in the lungs. These results implicate the adenosine A3 receptor in the pathogenesis of emphysema. Our findings also demonstrate the potential of LJ-2698 as a novel therapeutic/preventive agent in suppressing disease development with limited toxicity.

Hydroxyapatite Nanorod-Modified Sand Blasted Titanium Disk for Endosseous Dental Implant Applications

BACKGROUND: Sand blasted titanium (Ti) is commonly used in designing endosseous dental implants due to its biocompatibility and ability to form bonds with bone tissues. However, titanium implants do not induce strong interactions with teeth bones. To increase strong interactions between Ti disk implants and teeth bones, the L-glutamic acid grafted hydroxyapatite nanorods (nHA) were immobilized on albumin modified Ti disk implants (Ti-Alb). METHODS: For modification of Ti disk implants by nHA, the L-glutamic acid grafted nHA was synthesized and then immobilized on albumin modified Ti disk implants. Fourier transformed infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron microscope; energy dispersive spectroscopy and confocal laser scanning microscopy were used to confirm the modification of Ti disk implants. The bioactivity of nHA-modified Ti disk implants was evaluated by seeding MC3T3-E1 cells on Ti-nHA implants. RESULTS: Characterization techniques have confirmed the successful modification of Ti disk implants by L-glutamic acid grafted nHA. The nHA-modified Ti disk implants have shown enhanced adhesion, proliferation and cytotoxicity of MC3T3-E1 cells in comparison to pristine Ti implants. CONCLUSION: The modification of Ti implants by L-glutamic acid grafted nHA has produced highly osteogenic Ti disk plants in comparison to pristine Ti disk implants due to the formation of bioactive surfaces by hydroxyapatite nano rods on Ti disk implants. Ti-nHA disk implants showed enhanced adhesion, proliferation, and MC3T3-E1 cells viability in comparison to pristine Ti disk implants. Thus nHA might be to be useful to enhance the osseointegration of Ti implants with teeth bones.

Factors Related with Utilizing Hospice Palliative Care Unit among Terminal Cancer Patients in Korea between 2010 and 2014: a Single Institution Study

BACKGROUND: Establishing and designating specialized hospice palliative care units (HPCUs) has been an important part of national policy to promote hospice palliative care in Korea in the recent decade. However, few studies have sought to identify patterns and barriers for utilizing HPCU over the period of national policy implementation. We aimed to investigate factors related with utilizing HPCU for terminal cancer patients after consultation with a palliative care team (PCT). METHODS: We reviewed medical records for 1,028 terminal cancer patients who were referred to the PCT of the National Cancer Center in 2010 and 2014. We compared the characteristics of the patients who decided to utilize HPCU and those who did not. We also analyzed factors influencing choices for a medical institution and reasons for not selecting an HPCU. RESULTS: The patients' mean age was 61.0 ± 12.2, with lung cancer patients (24.3%) comprising the largest percentage of these patients. The percentage of referred patients who utilized an HPCU was 53.9% in 2014, increasing from 44.6% in 2010. Older age and awareness of terminal illness were found to be positively associated with utilization of an HPCU. The most common reason for not selecting an HPCU was “refusing hospice facility” (34.9%), followed by “near death,”“poor accessibility to an HPCU,” and “caregiving problems.” CONCLUSION: Compared to 2010, HPCU utilization by terminal cancer patients increased in 2014. Improving awareness of terminal condition among patients and family members and earlier discussion of end-of-life care would be important to promote utilization of HPCU.

Antitumor Effect of KX-01 through Inhibiting Src Family Kinases and Mitosis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: KX-01 is a novel dual inhibitor of Src and tubulin. Unlike previous Src inhibitors that failed to show clinical benefit during treatment of breast cancer, KX-01 can potentially overcome the therapeutic limitations of current Src inhibitors through inhibition of both Src and tubulin. The present study further evaluates the activity and mechanism of KX-01 in vitro and in vivo. MATERIALS AND METHODS: The antitumor effect of KX-01 in triple negative breast cancer (TNBC) cell lines was determined by MTT assay. Wound healing and immunofluorescence assays were performed to evaluate the action mechanisms of KX-01. Changes in the cell cycle and molecular changes induced by KX-01 were also evaluated. A MDA-MB-231 mouse xenograft model was used to demonstrate the in vivo effects. RESULTS: KX-01 effectively inhibited the growth of breast cancer cell lines. The expression of phospho-Src and proliferative-signaling molecules were down-regulated in KX-01-sensitive TNBC cell lines. In addition, migration inhibition was observed by wound healing assay. KX-01-induced G2/M cell cycle arrest and increased the aneuploid cell population in KX-01-sensitive cell lines. Multi-nucleated cells were significantly increased after KX-01 treatment. Furthermore, KX-01 effectively delayed tumor growth in a MDA-MB-231 mouse xenograft model. CONCLUSION: KX-01 effectively inhibited cell growth and migration of TNBC cells. Moreover, this study demonstrated that KX-01 showed antitumor effects through the inhibition of Src signaling and the induction of mitotic catastrophe. The antitumor effects of KX-01 were also demonstrated in vivo using a mouse xenograft model.

Do Korean Doctors Think a Palliative Consultation Team Would Be Helpful to Their Terminal Cancer Patients? / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Hospice and palliative care services (HPC) are not commonly utilized in Korea; however, palliative care teams (PCTs) have been found to be effective at addressing the shortcomings in HPC. In this study, we attempted to outline unmet palliative care needs of terminal cancer patients and the potential benefits of PCTs as perceived by doctors in Korea. MATERIALS AND METHODS: We surveyed 474 doctors at 10 cancer-related academic conferences from June to November 2014 with a self-report questionnaire to assess their perceptions of end-of-life care needs and the expected effects of PCTs on caring for terminal cancer patients. Among those surveyed, 440 respondents who completed the entire questionnaire were analyzed. RESULTS: In all domains, fewer participants reported satisfaction with palliative care services than those reporting needs (p < 0.001). The surveyed participants also reported difficulties with a shortage of time for treatment, psychological burden, lack of knowledge regarding hospice care, lengths of stay, and palliative ward availability. Multivariate logistic regression analysis revealed that female doctors (odds ratio [OR], 2.672; 95% confidence interval [CI], 1.035 to 6.892), doctors who agreed that referring my patients to a HPC means I must give up on my patient (OR, 3.075; 95% CI, 1.324 to 7.127), and doctors who had no experience with HPC education (OR, 3.337; 95% CI, 1.600 to 7.125) were associated with higher expected effectiveness of PCT activities. CONCLUSION: The PCT activities were expected to fill the doctor’s perceived unmet HPC needs of terminal cancer patients and difficulties in communications.

Effects of Vitamin and Antioxidant Supplements in Prevention of Bladder Cancer: a Meta-Analysis of Randomized Controlled Trials

This study aimed to investigate the effects of vitamin and antioxidant supplements in the prevention of bladder cancer using a meta-analysis of randomized controlled trials (RCTs). Fourteen RCTs were included in the final analysis. In a fixed-effect meta-analysis, vitamin and antioxidant supplements showed no preventive effect for bladder cancer (relative risk [RR] = 1.04; 95% confidence interval [CI] 0.92–1.17; I² = 39.7%). Also, there was no preventive effect of these supplements in the subgroup meta-analyses by various factors such as type of supplements, type of cancer prevention, methodological quality, providers of supplements, type of control group, and number of participants. Among the subgroup analyses by type of supplements, beta-carotene supplementation alone marginally increased the risk of bladder cancer (RR = 1.44; 95% CI 1.00–2.09; I² = 0.0%; n = 3). The current meta-analysis found that vitamin and antioxidant supplements have no preventive effect against bladder cancer.

Autophagy Regulates Formation of Primary Cilia in Mefloquine-Treated Cells

Primary cilia have critical roles in coordinating multiple cellular signaling pathways. Dysregulation of primary cilia is implicated in various ciliopathies. To identify specific regulators of autophagy, we screened chemical libraries and identified mefloquine, an anti-malaria medicine, as a potent regulator of primary cilia in human retinal pigmented epithelial (RPE) cells. Not only ciliated cells but also primary cilium length was increased in mefloquine-treated RPE cells. Treatment with mefloquine strongly induced the elongation of primary cilia by blocking disassembly of primary cilium. In addition, we found that autophagy was increased in mefloquine-treated cells by enhancing autophagic flux. Both chemical and genetic inhibition of autophagy suppressed ciliogenesis in mefloquine-treated RPE cells. Taken together, these results suggest that autophagy induced by mefloquine positively regulates the elongation of primary cilia in RPE cells.

Malignant mesothelioma mistaken for tuberculous pleurisy / 영남의대학술지

Malignant mesothelioma is a common, primary tumor that can invade pleura, and is associated with previous exposure to asbestos. However, it poses considerable difficulties regarding its diagnosis and treatment, and thus, accurate history taking with respect to exposure to asbestos, and radiologic and pathologic examinations are essential. In addition, the involvement of a multidisciplinary team is recommended in order to ensure prompt and appropriate management using a framework based on radiotherapy, chemotherapy, surgery, and symptom palliation with end-of-life care. Because lymphocyte-dominant, exudative pleural effusion can occur in malignant mesothelioma, adenosine deaminase values may be elevated, which could be mistaken for tuberculous pleurisy, and lead to an incorrect diagnosis and suboptimal treatment. The authors describe a case of malignant mesothelioma initially misdiagnosed as tuberculous pleurisy. As evidenced by the described case, malignant mesothelioma should be considered during the differential diagnosis of patients with lymphocyte-dominant, exudative pleural effusion with a pleural lung lesion.

Endoscopic Ultrasound-Guided Transesophageal Drainage of a Mediastinal Pancreatic Pseudocyst / 대한췌담도학회지

Pancreatic pseudocyst is a common complication of acute/chronic pancreatitis, but extension of a pancreatic pseudocyst into the mediastinum is a rare occurrence. In this report, we described a case of a 62-year-old male with necrotizing pancreatitis presenting with chest pain and dysphagia caused by a mediastinal pseudocyst. Endoscopic retrograde pancreatography revealed pancreatic duct disruption and leaks. A mediastinal pseudocyst was successfully drained by endoscopic ultrasound (EUS)-guided transesophageal approach. Chest pain and dysphagia disappeared swiftly with drainage. Associated pancreatic pseudocyst at tail was managed by EUS-guided cystogastrostomy and pleural effusion was controlled by percutaneous drainage, respectively. In a follow-up period of 3 months, there has been no recurrence of symptoms and signs. Although currently EUS-guided transesophageal approach was done in the selected cases, this procedure is technically feasible, less invasive and more effective than surgical approach.

Comparative study on medical fees: caesarean section, cataract, and appendectomy surgeries among OECD countries

The question has been raised whether the medical fee schedule is very low in Korea. However, studies that empirically address this matter on a national scale are rare. This study attempted to determine the level of Korea's medical fees for caesarean section (C-section), cataract, and appendectomy surgeries by comparing and analyzing them with other Organization for Economic Cooperation and Development (OECD) countries' medical cost data obtained from other studies. There are two ways to compare the level of medical fees: one is a direct comparison, which obtains each country's medical fee schedule and compares them with each other. Another is indirect comparison, a method which compares data such as physician income. For direct comparison, fees were calculated using data provided by the OECD and Health Insurance Review and Assessment. For indirect comparison by physician income, data obtained from Korea Employment Information Services were used to represent Korean physician income. When compared with other OECD countries, the results suggest that, overall, the Korean fee schedule could be low, based on the fees for C-section, cataract, and appendectomy surgeries. The study results also confirm that Korean physicians' average earnings ranked relatively low among OECD countries. These results are meaningful in that they empirically support the contention that Korean medical fees could be low. In addition, under what is known as national health insurance, in which the medical fee schedule is determined by a single payer, an empirical analysis on medical fee levels, as in this study, has substantial political implications because it may be utilized for medical fee schedule negotiation in the near future. An attempt to directly research fees and the range of services of OECD countries is still needed in order to provide more established data.

Down-Regulation of Survivin by Nemadipine-A Sensitizes Cancer Cells to TRAIL-Induced Apoptosis

The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor family of cytokines. TRAIL selectively induces apoptotic cell death in various tumors and cancer cells, but it has little or no toxicity in normal cells. Agonism of TRAIL receptors has been considered to be a valuable cancer-therapeutic strategy. However, more than 85% of primary tumors are resistant to TRAIL, emphasizing the importance of investigating how to overcome TRAIL resistance. In this report, we have found that nemadipine-A, a cell-permeable L-type calcium channel inhibitor, sensitizes TRAIL-resistant cancer cells to this ligand. Combination treatments using TRAIL with nemadipine-A synergistically induced both the caspase cascade and apoptotic cell death, which were blocked by a pan caspase inhibitor (zVAD) but not by autophagy or a necrosis inhibitor. We further found that nemadipine-A, either alone or in combination with TRAIL, notably reduced the expression of survivin, an inhibitor of the apoptosis protein (IAP) family of proteins. Depletion of survivin by small RNA interference (siRNA) resulted in increased cell death and caspase activation by TRAIL treatment. These results suggest that nemadipine-A potentiates TRAIL-induced apoptosis by down-regulation of survivin expression in TRAIL resistant cells. Thus, combination of TRAIL with nemadipine-A may serve a new therapeutic scheme for the treatment of TRAIL resistant cancer cells, suggesting that a detailed study of this combination would be useful.

Fatal Rhabdomyolysis in a Patient with Liver Cirrhosis after Switching from Simvastatin to Fluvastatin

HMG-CoA reductase inhibitors (statins) are widely used to treat hypercholesterolemia. Among the adverse effects associated with these drugs are statin-associated myopathies, ranging from asymptomatic elevation of serum creatine kinase to fatal rhabdomyolysis. Fluvastatin-induced fatal rhabdomyolysis has not been previously reported. We describe here a patient with liver cirrhosis who experienced fluvastatin-induced fatal rhabdomyolysis. This patient had been treated with simvastatin (20 mg/day) for coronary artery disease and was switched to fluvastatin (20 mg/day) 10 days before admission. He was also taking aspirin, betaxolol, candesartan, lactulose, and entecavir. Rhabdomyolysis was complicated and continued to progress. He was treated with massive hydration, urine alkalization, intravenous furosemide, and continuous renal replacement therapy for acute renal failure, but eventually died due to rhabdomyolysis complicated by hepatic failure. In conclusion, fluvastatin should be used with caution in patients with liver cirrhosis, especially with other medications metabolized with CYP2C9.

Study of serum levels of estradiol, progesterone and ?hCG compare ectopic pregnancy with normal pregnancy / 대한산부인과학회잡지

No abstract available.