Publications by authors named "Kyung Hoon Kim"

113 Publications

Platycodin D attenuates airway inflammation via suppression Th2 transcription factor in a murine model of acute asthma.

J Asthma 2021 Jun 23:1-11. Epub 2021 Jun 23.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Bronchial asthma is a common chronic inflammatory condition of the airway tissue. Platycodin D (PLD) has antiinflammatory effects in a mouse model of allergic asthma. In this work, the anti-asthma potential of PLD was studied by investigation of its effect to suppress airway inflammation and mucin production, a murine model of asthma and the possible mechanisms. Mice were randomly assigned to five experimental groups: control, ovalbumin (OVA), OVA+ICS (intranasal fluticasone), OVA+PLD and OVA+PLD/ICS. Airway histological studies were evaluated by the H&E staining; IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid were evaluated by ELISA; GATA3 and IRF4 mRNA of airway were measured by RT-PCR and their protein level were measured by Western blotting. Our study showed that PLD suppressed eosinophilic inflammation and mucin production in bronchial mucosa. Moreover, PLD inhibited production of Th2 cytokines such as IL-4, IL-5, and IL-13. Protein production of GATA3 and IRF4, were also decreased in PLD treated OVA asthma model. Taken together, our results provided evidence that PLD inhibits the airway inflammation via suppression of Th2 transcription factor production. These findings suggest that PLD may effectively ameliorate the progression of asthma. These results suggest that PLD could be used as a therapy for allergic asthma.
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http://dx.doi.org/10.1080/02770903.2021.1941084DOI Listing
June 2021

3D Hierarchical Nanotopography for On-Site Rapid Capture and Sensitive Detection of Infectious Microbial Pathogens.

ACS Nano 2021 03 27;15(3):4777-4788. Epub 2021 Jan 27.

Division of Nano-Bio Sensors/Chips Development, National NanoFab Center (NNFC), Daejeon 34141, Republic of Korea.

Effective capture and rapid detection of pathogenic bacteria causing pandemic/epidemic diseases is an important task for global surveillance and prevention of human health threats. Here, we present an advanced approach for the on-site capture and detection of pathogenic bacteria through the combination of hierarchical nanostructures and a nuclease-responsive DNA probe. The specially designed hierarchical nanocilia and network structures on the pillar arrays, termed 3D bacterial capturing nanotopographical trap, exhibit excellent mechanical reliability and rapid (<30 s) and irreversible bacterial capturability. Moreover, the nuclease-responsive DNA probe enables the highly sensitive and extremely fast (<1 min) detection of bacteria. The bacterial capturing nanotopographical trap (b-CNT) facilitates the on-site capture and detection of notorious infectious pathogens ( O157:H7, , , and ) from kitchen tools and food samples. Accordingly, the usefulness of the b-CNT is confirmed as a simple, fast, sensitive, portable, and robust on-site capture and detection tool for point-of-care testing.
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http://dx.doi.org/10.1021/acsnano.0c09411DOI Listing
March 2021

Influence of Fluorine Doping of Activated Carbon Fibers on Their Water Vapor Adsorption Characteristics.

Front Chem 2020 6;8:593756. Epub 2021 Jan 6.

Department of Chemistry, Royal Military Academy, Brussels, Belgium.

The characterization of fluorinated carbon fibers by water sorption has been broadly investigated in this work. In brief, a pitch-based activated carbon fiber (ACF) was submitted to a fluorination process under different conditions of partial pressure (F:N ratio) and temperature. This led to samples with varied fluorine content and C-F type bonding. The effect of the fluorination treatment on the textural properties of the ACF was studied by means of nitrogen and carbon dioxide adsorption at -196 and 0°C, respectively, while the changes induced in the surface chemistry of the materials were analyzed by XPS. Also, the affinity and stability of the materials toward water was evaluated by single and cycling isotherms. The obtained results show that a mild fluorination not only can preserve most of the textural properties of the parent ACF, but enhance the water uptake at the first stages of the water sorption process, together with a shift in the upswing of the water isotherms toward lower relative humidities. This indicates that fluorination under certain conditions can actually enhance the surface hydrophilicity of carbon materials with specific properties. On the contrary, higher partial pressures led to highly fluorinated fibers with lower porosity and more hydrophobic character. Moreover, they presented a lower chemical stability as demonstrated by a change in the shape of the water isotherms after two consecutive measurements. The kinetics of water sorption in the ACFs provided further insights into the different sorption phenomena involved. Hence, water sorption can definitely help to tailor the water affinity, stability and performance of fluorinated porous carbon materials under humid conditions.
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http://dx.doi.org/10.3389/fchem.2020.593756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7821472PMC
January 2021

The Association between Dynamic Changes in Serum Presepsin Levels and Mortality in Immunocompromised Patients with Sepsis: A Prospective Cohort Study.

Diagnostics (Basel) 2021 Jan 2;11(1). Epub 2021 Jan 2.

Department of Laboratory Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea.

Presepsin is a subtype of soluble CD14 that is increased in the blood of septic patients. We investigated the role of dynamic changes in serum presepsin levels in critically ill, immunocompromised patients with sepsis. This is a prospective cohort study that included 119 adult patients admitted to the intensive care unit (ICU). Presepsin level was measured on day 1 and day 3 after ICU admission. The primary outcome was in-hospital mortality. In immunocompromised patients, presepsin levels on day 1 were higher in patients with sepsis than those in patients without sepsis. The area under the curve (AUC) of presepsin for diagnosing sepsis in immunocompromised patients was 0.87, which was comparable with that of procalcitonin (AUC, 0.892). Presepsin levels on day 3 were higher in patients who died in the hospital than in those who survived. In immunocompromised patients who died in the hospital, presepsin levels on day 3 were significantly higher than those on day 1. In the multivariate analysis, ΔPresepsin+ alone was independently correlated with in-hospital mortality in immunocompromised patients. These findings suggest that dynamic changes in presepsin levels between day 1 and day 3 are associated with in-hospital mortality in patients with sepsis, especially in immunocompromised patients.
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http://dx.doi.org/10.3390/diagnostics11010060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823693PMC
January 2021

Mirogabalin: could it be the next generation gabapentin or pregabalin?

Korean J Pain 2021 Jan;34(1):4-18

Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.

Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.
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http://dx.doi.org/10.3344/kjp.2021.34.1.4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783847PMC
January 2021

Efficacy and safety of high-dose budesonide/formoterol in patients with bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplant.

J Thorac Dis 2020 Aug;12(8):4183-4195

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Seoul St Mary's Hospital, The Catholic University of Korea, Seoul, Korea.

Background: Bronchiolitis obliterans syndrome (BOS) is a rare, progressive and irreversible airway disease associated with significant mortality after allogeneic hematopoietic stem-cell transplantation (HSCT). In this study, we investigated the therapeutic effect of high-dose budesonide/formoterol (320/9 µg bid) in patients with BOS after HSCT already using low-dose budesonide/formoterol (160/4.5 µg bid).

Methods: After a retrospective chart review, patients who were initially treated with budesonide/formoterol 160/4.5 µg bid and increased their dose to 320/9 µg bid between March 2009 and February 2019 were enrolled. Pulmonary function test (PFT) and COPD assessment test (CAT) were performed before and after changing the drug dose. Efficacy was assessed within 3 months after increasing the drug dose; the primary variable was changes in forced expiratory volume in 1 second (FEV1) and CAT score. Safety was assessed as the incidence of pneumonia within 3 months after increasing the drug dose.

Results: Seventy-seven patients were treated with budesonide 160 µg plus formoterol 4.5 µg twice a day for more than 3 months and the dose was increased to budesonide 320 µg plus 9.0 µg twice a day. After treatment with high-dose ICS/LABA (budesonide 320 µg plus formoterol 9.0 µg twice a day for 12 weeks), there were no significant differences in FEV1 (before treatment 1.59 L after treatment 1.65 L, P=0.182) or FVC (before treatment 2.93 L after treatment 2.96 L, P=0.519) compared to before starting the high dose treatment. There were no significant differences in the total CAT score. Of all patients, 34.2% of patients had an increase in FEV1 ≥100 mL and 35.3% of patients showed a decrease ≥2 points in CAT score. In safety assessment, there were no significant differences between the two periods.

Conclusions: Our study failed to show superior effect of high-dose budesonide/formoterol (320/9 µg) compared with low-dose. However, high-dose budesonide/formoterol was safe and there was no lung function deterioration.
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http://dx.doi.org/10.21037/jtd-19-3475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475605PMC
August 2020

All about pain pharmacology: what pain physicians should know.

Korean J Pain 2020 Apr;33(2):108-120

Department of Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

From the perspective of the definition of pain, pain can be divided into emotional and sensory components, which originate from potential and actual tissue damage, respectively. The pharmacologic treatment of the emotional pain component includes antianxiety drugs, antidepressants, and antipsychotics. The anti-anxiety drugs have anti-anxious, sedative, and somnolent effects. The antipsychotics are effective in patients with positive symptoms of psychosis. On the other hand, the sensory pain component can be divided into nociceptive and neuropathic pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are usually applied for somatic and visceral nociceptive pain, respectively; anticonvulsants and antidepressants are administered for the treatment of neuropathic pain with positive and negative symptoms, respectively. The NSAIDs, which inhibit the cyclo-oxygenase pathway, exhibit anti-inflammatory, antipyretic, and analgesic effects; however, they have a therapeutic ceiling. The adverse reactions (ADRs) of the NSAIDs include gastrointestinal problems, generalized edema, and increased bleeding tendency. The opioids, which bind to the opioid receptors, present an analgesic effect only, without anti-inflammatory, antipyretic, or ceiling effects. The ADRs of the opioids start from itching and nausea/vomiting to cardiovascular and respiratory depression, as well as constipation. The anticonvulsants include carbamazepine, related to sodium channel blockade, and gabapentin and pregabalin, related to calcium blockade. The antidepressants show their analgesic actions mainly through inhibiting the reuptake of serotonin or norepinephrine. Most drugs, except NSAIDs, need an updose titration period. The principle of polypharmacy for analgesia in case of mixed components of pain is increasing therapeutic effects while reducing ADRs, based on the origin of the pain.
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http://dx.doi.org/10.3344/kjp.2020.33.2.108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136290PMC
April 2020

Effects of Intraoperative Low-Dose Ketamine on Persistent Postsurgical Pain after Breast Cancer Surgery: A Prospective, Randomized, Controlled, Double-Blind Study.

Pain Physician 2020 01;23(1):37-47

Department of Statistics, Pusan National University, Busan, Republic of Korea.

Background: Compared to acute postsurgical pain, studies regarding the role of ketamine in persistent postsurgical pain (PPSP) are limited.

Objectives: The aim of this clinical trial was to test if intraoperative low-dose ketamine without postoperative infusion would reduce PPSP development after breast cancer surgery.

Study Design: We used a randomized, double-blinded, placebo study design.

Setting: This study was conducted at Pusan National University Hospital, Republic of Korea, between December 2013 and August 2016.

Methods: A total of 184 patients scheduled for breast cancer surgery were randomly assigned to either the control or ketamine group. Before skin incision, a bolus (0.5 mg/kg of ketamine or placebo), followed by a continuous infusion (0.12 mg/kg/h of ketamine or placebo), was administered until the end of the surgery. The patients were interviewed via telephone 1, 3, and 6 months after surgery. The first question was whether the patient had surgery-related pain. If answered affirmatively, questions from the Numeric Rating Scale for pain at rest (NRSr) and for coughing (NRSd) were also asked. Our primary outcome was the incidence of PPSP at 3 months after surgery.

Results: For PPSP analysis, 168 patients were included. The number of patients who experienced pain was significantly lower in the ketamine group at 3 months (86.9% in the control group vs 69.0% in the ketamine group, P = .005) postoperatively. However, the NRSr and NRSd did not differ between the groups throughout the follow-up.

Limitations: There were no postoperative low-dose ketamine infusion groups to compare due to hospital regulations. Dosage of ketamine was too low to reduce the severity of PPSP. And by using propofol and remifentanil for anesthesia, different results can be deduced with volatile anesthetics. Data from written questionnaires would have been more specific than telephone interviews for long-term assessment.

Conclusions: Though intraoperative low-dose ketamine without postoperative infusion significantly reduced the incidence of PPSP up to 3 months after breast cancer surgery, it failed to reduce clinically significant PPSP and improve patients' quality of life.

Key Words: Analgesia, breast cancer, chronic pain, ketamine, mastectomy, morphine, pain, postoperative, propofol.
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January 2020

Stem cell therapy in pain medicine.

Korean J Pain 2019 Oct;32(4):245-255

Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.

Stem cells are attracting attention as a key element in future medicine, satisfying the desire to live a healthier life with the possibility that they can regenerate tissue damaged or degenerated by disease or aging. Stem cells are defined as undifferentiated cells that have the ability to replicate and differentiate themselves into various tissues cells. Stem cells, commonly encountered in clinical or preclinical stages, are largely classified into embryonic, adult, and induced pluripotent stem cells. Recently, stem cell transplantation has been frequently applied to the treatment of pain as an alternative or promising approach for the treatment of severe osteoarthritis, neuropathic pain, and intractable musculoskeletal pain which do not respond to conventional medicine. The main idea of applying stem cells to neuropathic pain is based on the ability of stem cells to release neurotrophic factors, along with providing a cellular source for replacing the injured neural cells, making them ideal candidates for modulating and possibly reversing intractable neuropathic pain. Even though various differentiation capacities of stem cells are reported, there is not enough knowledge and technique to control the differentiation into desired tissues . Even though the use of stem cells is still in the very early stages of clinical use and raises complicated ethical problems, the future of stem cells therapies is very bright with the help of accumulating evidence and technology.
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http://dx.doi.org/10.3344/kjp.2019.32.4.245DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813895PMC
October 2019

A Staged Treatment of Symptomatic Lumbar Intraspinal Synovial Cysts.

Pain Physician 2019 09;22(5):E451-E456

Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea.

Background: Lumbar intraspinal synovial cyst (LISC) refers to a cyst that arises from the zygapophyseal joint capsule of the lumbar spine and contains serous or gelatinous fluid. In cases of LISCs resistant to conservative treatments, various minimally invasive percutaneous spinal techniques (MIPSTs) may be applied prior to open surgery.

Objectives: The outcomes of 3-staged MIPSTs for the treatment of symptomatic LISCs resistant to conservative treatments were evaluated.

Study Design: An institutional review board approved retrospective chart review.

Setting: University hospital inpatients referred to our pain clinic.

Methods: Review of charts of all patients who underwent MIPSTs for symptomatic LISCs resistant to conservative treatments during a time period of 13 years at a university hospital pain clinic. Patients with symptomatic LISCs resistant to conservative treatments were treated with 3-staged MIPSTs, including image-guided intraarticular aspiration, cyst distention and rupture, and injection of corticosteroids (ARI), endoscopic cyst enucleation (ECE), and endoscopic superior facetectomy (ESF) by a single pain specialist. A symptom-free period after each intervention was evaluated. Recurrence was defined as the same recurrent symptomatic radicular pain with confirmation of the LISC on magnetic resonance imaging. All patients with a minimum follow-up time of 3 years were included.

Results: Of the 40 patients who underwent ARI, 3 patients failed to complete a follow-up and 19 patients (51.4%) who had recurring symptoms received ECE. Ten patients (52.6%) who had re-recurring symptoms after ECE received ESF. There was no recurrence after ESF.

Limitations: This retrospective and observational study with a limited number of patients does not represent a high level of evidence.

Conclusions: This information provided the recurrence rate after each intervention. Half of the patients who went on to receive ARI experienced recurrence, whereas half of the patients with recurrence who received ECE experienced re-recurrence. ESF treatment resulted in no recurrence within the 3-year study period.

Key Words: Conservative treatment, endoscopic surgical procedures, facet joint, intraarticular injection, minimally invasive surgical procedures, needle biopsy, nerve root compression, radiculopathy, synovial cysts.
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September 2019

Impacts of whey protein on starch digestion in rumen and small intestine of steers.

J Anim Sci Technol 2019 03 31;61(2):98-108. Epub 2019 Mar 31.

Department of Animal Science and Technology, Sanghuh College of Life Sciences, Konkuk University, Seoul 05029, Korea.

Four Korean native steers (511 ± 17.2 kg; 2 × 2 replicated crossover design) fitted with duodenal cannulas were used to investigate the influence of oral administration of soluble whey protein (WP; 82.29% crude protein) on ruminal fermentation, gastrointestinal (GI) hormone secretion in the blood, pancreatic α-amylase activity in the duodenum, and disappearance rate in each segment of the GI tract. Steers were orally fed the basal diet (control; TMR [total mixed ration] 9 kg/d) or the basal diet with enriched WP (400 g/d) for 14 days. The apparent crude protein disappearance rate in the rumen of the WP was higher than in control ( < 0.05). However, no difference between groups was observed in the apparent crude protein disappearance rate in the intestine and the apparent starch disappearance rates in the rumen, GI tract. The level of cholecystokinin, secretin, and ghrelin in serum and pancreatic α-amylase activity in the duodenum of the WP also did not change. The changes in the level of blood urea nitrogen related to protein metabolism were higher in the WP than in the control ( < 0.05). However, the levels of total protein, lipid, carbohydrate and mineral metabolites did not change. Consequently, we suggest that the oral administration of WP in steers assisted in ruminal fermentation due to the population increase of microbes in the rumen but did not improve the starch digestion rate in the small intestine because GI hormone secretion in the blood and pancreatic α-amylase activity did not change.
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http://dx.doi.org/10.5187/jast.2019.61.2.98DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582930PMC
March 2019

Nonclinical safety evaluation of erenumab, a CGRP receptor inhibitor for the prevention of migraine.

Regul Toxicol Pharmacol 2019 Aug 11;106:224-238. Epub 2019 May 11.

Amgen Research, One Amgen Center Dr., Thousand Oaks, CA, 91320, USA.

Calcitonin gene-related peptide (CGRP) and its receptor have been implicated as a key mediator in the pathophysiology of migraine. Thus, erenumab, a monoclonal antibody antagonist of the CGRP receptor, administered as a once monthly dose of 70 or 140 mg has been approved for the preventive treatment of migraine in adults. Due to the species specificity of erenumab, the cynomolgus monkey was used in the pharmacology, pharmacokinetics, and toxicology studies to support the clinical program. There were no effects of erenumab on platelets in vitro (by binding, activation or phagocytosis assays). Specific staining of human tissues with erenumab did not indicated any off-target binding. There were no erenumab-related findings in a cardiovascular safety pharmacology study in cynomolgus monkeys or in vitro in human isolated coronary arteries. Repeat-dose toxicology studies conducted in cynomolgus monkeys at dose levels up to 225 mg/kg (1 month) or up to 150 mg/kg (up to 6 months) with twice weekly subcutaneous (SC) doses showed no evidence of erenumab-mediated adverse toxicity. There were no effects on pregnancy, embryo-fetal or postnatal growth and development in an enhanced pre-postnatal development study in the cynomolgus monkey. There was evidence of placental transfer of erenumab based on measurable serum concentrations in the infants up to 3 months post birth. The maternal and developmental no-observed-effect level (NOEL) was the highest dose tested (50 mg/kg SC Q2W). These nonclinical data in total indicate no safety signal of concern to date and provide adequate margins of exposure between the observed safe doses in animals and clinical dose levels.
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http://dx.doi.org/10.1016/j.yrtph.2019.05.013DOI Listing
August 2019

Successful removal of permanent spinal cord stimulators in patients with complex regional pain syndrome after complete relief of pain.

Korean J Pain 2019 Jan 2;32(1):47-50. Epub 2019 Jan 2.

Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea.

Background: It is uncommon for patients who have received a permanent implant to remove the spinal cord stimulator (SCS) after discontinuation of medication in complex regional pain syndrome (CRPS) due to their completely painless state. This study evaluated CRPS patients who successfully removed their SCSs.

Methods: This 10-year retrospective study was performed on patients who had received the permanent implantation of an SCS and had removed it 6 months after discontinuation of stimulation, while halting all medications for neuropathic pain. Age, sex, duration of implantation, site and type of CRPS, and their return to work were compared between the removal and non-removal groups.

Results: Five (12.5%, M/F = 4/1) of 40 patients (M/F = 33/7) successfully removed the permanent implant. The mean age was younger in the removal group (27.2 ± 6.4 vs. 43.5 ± 10.7 years, < 0.01). The mean duration of implantation in the removal group was 34.4 ± 18.2 months. Two of 15 patients (13.3%) and 3 of 25 patients (12%) who had upper and lower extremity pain, respectively, had removed the implant. The implants could be removed in 5 of 27 patients (18.5%) with CRPS type 1 ( < 0.01). All 5 patients (100%) who removed their SCS returned to work, while only 5 of 35 (14.3%) in the non-removal group did ( < 0.01).

Conclusions: Even though this study had limited data, younger patients with CRPS type 1 could remove their SCSs within a 5-year period and return to work with complete pain relief.
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http://dx.doi.org/10.3344/kjp.2019.32.1.47DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333578PMC
January 2019

Antipsychotics for patients with pain.

Korean J Pain 2019 Jan 2;32(1):3-11. Epub 2019 Jan 2.

Department of Anesthesia and Pain Medicine, Pusan National University, Busan, Korea.

Going back to basics prior to mentioning the use of antipsychotics in patients with pain, the International Association for the Study of Pain (IASP) definition of pain can be summarized as an unpleasant experience, composed of sensory experience caused by actual tissue damage and/or emotional experience caused by potential tissue damage. Less used than antidepressants, antipsychotics have also been used for treating this unpleasant experience as adjuvant analgesics without sufficient evidence from research. Because recently developed atypical antipsychotics reduce the adverse reactions of extrapyramidal symptoms, such as acute dystonia, pseudo-parkinsonism, akathisia, and tardive dyskinesia caused by typical antipsychotics, they are expected to be used more frequently in various painful conditions, while increasing the risk of metabolic syndromes (weight gain, diabetes, and dyslipidemia). Various antipsychotics have different neurotransmitter receptor affinities for dopamine (D), 5-hydroxytryptamine (5-HT), adrenergic (α), histamine (H), and muscarinic (M) receptors. Atypical antipsychotics antagonize transient, weak D receptor bindings with strong binding to the 5-HT receptor, while typical antipsychotics block long-lasting, tight D receptor binding. On the contrary, antidepressants in the field of pain management also block the reuptake of similar receptors, mainly on the 5-HT and, next, on the norepinephrine, but rarely on the D receptors. Antipsychotics have been used for treating positive symptoms, such as delusion, hallucination, disorganized thought and behavior, perception disturbance, and inappropriate emotion, rather than the negative, cognitive, and affective symptoms of psychosis. Therefore, an antipsychotic may be prescribed in pain patients with positive symptoms of psychosis during or after controlling all sensory components.
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http://dx.doi.org/10.3344/kjp.2019.32.1.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333575PMC
January 2019

Propofol promotes osteoclastic bone resorption by increasing DC-STAMP expression.

J Dent Anesth Pain Med 2018 Dec 28;18(6):349-359. Epub 2018 Dec 28.

Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea.

Background: Propofol is an intravenous anesthetic which has antioxidant effects due to its similarity in molecular structure to α-tocopherol. It has been reported that α-tocopherol increases osteoclast fusion and bone resorption. Here, we investigated the effects of propofol on signaling pathways of osteoclastogenic gene expression, as well as osteoclastogenesis and bone resorption using bone marrow-derived macrophages (BMMs).

Methods: BMMs were cultured with macrophage colony-stimulating factor (M-CSF) alone or M-CSF plus receptor activator of nuclear factor kappa B ligand (RANKL) in the presence of propofol (0-50 µM) for 4 days. Mature osteoclasts were stained for tartrate-resistant acid phosphatase (TRAP) and the numbers of TRAP-positive multinucleated osteoclasts were counted. To examine the resorption activities of osteoclasts, a bone resorption assay was performed. To identify the mechanism of action of propofol on the formation of multinucleated osteoclasts, we focused on dendritic cell-specific transmembrane protein (DC-STAMP), a protein essential for pre-osteoclastic cell fusion.

Results: Propofol increased the formation of TRAP-positive multinucleated osteoclasts. In addition, the bone resorption assay revealed that propofol increased the bone resorption area on dentin discs. The mRNA expression of DC-STAMP was upregulated most strongly in the presence of both RANKL and propofol. However, SB203580, a p38 inhibitor, significantly suppressed the propofol/RANKL-induced increase in mRNA expression of DC-STAMP.

Conclusion: We have demonstrated that propofol enhances osteoclast differentiation and maturation, and subsequently increases bone resorption. Additionally, we identified the regulatory pathway underlying osteoclast cell-cell fusion, which was enhanced by propofol through p38-mediated DC-STAMP expression.
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http://dx.doi.org/10.17245/jdapm.2018.18.6.349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323039PMC
December 2018

The Effects of Thoracic Epidural Analgesia during Percutaneous Radiofrequency Ablation for Hepatocellular Carcinoma.

Pain Res Manag 2018 19;2018:4354912. Epub 2018 Nov 19.

Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Busan, Republic of Korea.

Background: Percutaneous radiofrequency ablation (PRFA) is a useful and safe treatment for hepatocellular carcinoma (HCC). Pain management, during and after PRFA, is a critical component of patient care.

Objectives: This study reviewed the efficacy of thoracic epidural analgesia, during and after PRFA, for patients with HCC.

Study Design: A retrospective, observational chart review.

Setting: Tertiary medical center/teaching hospital.

Methods: Patients who had undergone PRFA for HCC in the past 5 years were divided into two groups, based on the type of anesthesia administered: thoracic epidural anesthesia group (Group E) and local anesthesia with monitored anesthesia care group (Group C). We retrospectively reviewed changes in the numeric rating scale (NRS) score during and after PRFA, opioid consumption, length of the procedure, length of hospital stay, changes in blood pressure during PRFA, and the incidence of adverse events.

Results: The NRS score in Group E was significantly lower than that in Group C ( < 0.05). The opioid consumption in Group E was lower than that in Group C after PRFA ( < 0.05). The procedure time was shorter in Group E ( < 0.05). Neither of the groups showed significant difference with respect to the length of hospital stay and the incidence of respiratory depression, fever, and blood pressure elevation. The incidence of nausea, vomiting, and voiding difficulty was higher in Group E.

Limitations: This study is limited by its retrospective design.

Conclusions: Thoracic epidural analgesia was associated with shorter procedure times, lower postprocedural pain, and lower opioid consumption during and after PRFA for HCC.
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http://dx.doi.org/10.1155/2018/4354912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276420PMC
February 2019

Treatment of Chemotherapy-Induced Peripheral Neuropathy: Systematic Review and Recommendations.

Pain Physician 2018 11;21(6):571-592

University of Texas, MD Anderson Cancer Center, Houston, TX.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a commonly encountered disease entity following chemotherapy for cancer treatment. Although only duloxetine is recommended by the American Society of Clinical Oncology (ASCO) for the treatment of CIPN in 2014, the evidence of the clinical outcome for new pharmaceutic therapies and non-pharmaceutic treatments has not been clearly determined.

Objective: To provide a comprehensive review and evidence-based recommendations on the treatment of CIPN.

Study Design: A systematic review of each treatment regimen in patients with CIPN.

Methods: The literature on the treatment of CIPN published from 1990 to 2017 was searched and reviewed. The 2011 American Academy of Neurology Clinical Practice Guidelines Process Manual was used to grade the evidence and risk of bias. We reviewed and updated the recommendations of the ASCO in 2014, and evaluated new approaches for treating CIPN.

Results: A total of 26 treatment options in 35 studies were identified. Among these, 7 successful RCTs, 6 failed RCTs, 18 prospective studies, and 4 retrospective studies were included. The included studies examined not only pharmacologic therapy but also other modalities, including laser therapy, scrambler therapy, magnetic field therapy and acupuncture, etc. Most of the included studies had small sample sizes, and short follow-up periods. Primary outcome measures were highly variable across the included studies. No studies were prematurely closed owing to its adverse effects.

Limitations: The limitations of this systematic review included relatively poor homogeneous, with variations in timing of treatment, primary outcomes, and chemotherapeutic agents used.

Conclusion: The evidence is considered of moderate benefit for duloxetine. Photobiomodulation, known as low level laser therapy, is considered of moderate benefit based on the evidence review. Evidence did not support the use of lamotrigine and topical KA (4% ketamine and 2% amitriptyline). The evidence for tricyclic antidepressants was inconclusive as amitriptyline showed no benefit but nortriptyline had insufficient evidence. Further research on CIPN treatment is needed with larger sample sizes, long-term follow-up, standardized outcome measurements, and standardized treatment timing.

Key Words: Chemotherapy-induced neuropathy, peripheral neuropathy, chemotherapy-tumor, neuropathic pain, chronic pain, toxicology, treatment, reduction of pain, level of evidence.
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November 2018

Development of a BiTE-mediated CD8 cytotoxic T-lymphocyte activity assay to assess immunomodulatory potential of drug candidates in Cynomolgus macaque.

J Immunotoxicol 2018 12;15(1):119-125

a Comparative Biology and Safety Sciences , Amgen Inc. , South San Francisco , CA , USA.

The immunotoxic potential of drug candidates is assessed through the examination of results from a variety of studies and endpoints. While the functional assessment of CD8 cytotoxic T-lymphocytes (CTL) is well-characterized in the clinic, the lack of a robust macaque CTL functional assay has been an important hurdle in evaluating and accurately quantifying cell-mediated CD8 T-cell effector responses in the nonclinical setting. This paper describes the development of an assay to measure CTL activity in peripheral blood mononuclear cells (PBMC) isolated from Cynomolgus macaques. A human EGFR/CD3 Bispecific T-cell Engager (BiTE) was used to mount a robust CD8 T-cell response in the presence of target-expressing cells. Upon target engagement, degranulation of CD107a and production of interferon (IFN)-γ both reliably indicated a robust functional response in CD8 T-cells. The BiTE-mediated stimulation method proved to be favorable when compared to other methods of stimulation in the absence of target cells. These studies demonstrated acceptable longitudinal variability of the functional assay and sensitivity to dexamethasone-mediated immunosuppression. Taken together, the results indicated an assay leveraging CD3-bispecific antibodies and target-expressing cells can provide a robust approach to the in vitro or ex vivo assessment of CTL function in Cynomolgus macaques. Because the impairment of CTL activity by immunomodulators is recognized to be an important contributor to decreased antiviral defense and increased carcinogenicity risk, we believe that this novel assay to be a valuable addition to the immunotoxicology assessment of therapeutic drug candidates.
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http://dx.doi.org/10.1080/1547691X.2018.1486342DOI Listing
December 2018

Can oliceridine (TRV130), an ideal novel µ receptor G protein pathway selective (µ-GPS) modulator, provide analgesia without opioid-related adverse reactions?

Korean J Pain 2018 Apr 2;31(2):73-79. Epub 2018 Apr 2.

Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea.

All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to µ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the β-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the β-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the µ receptor G protein pathway selective (µ-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased µ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.
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http://dx.doi.org/10.3344/kjp.2018.31.2.73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904350PMC
April 2018

TRPV1 Blocking Alleviates Airway Inflammation and Remodeling in a Chronic Asthma Murine Model.

Allergy Asthma Immunol Res 2018 May;10(3):216-224

Division of Pulmonology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea.

Purpose: Asthma is a chronic inflammatory airway disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. There is emerging interest in the involvement of the transient receptor potential vanilloid 1 (TRPV1) channel in the pathophysiology of asthma. This study examined whether TRPV1 antagonism alleviates asthma features in a murine model of chronic asthma.

Methods: BALB/c mice were sensitized to and challenged by ovalbumin to develop chronic asthma. Capsazepine (TRPV1 antagonist) or TRPV1 small interfering RNA (siRNA) was administered in the treatment group to evaluate the effect of TPV1 antagonism on AHR, airway inflammation, and remodeling.

Results: The mice displayed increased AHR, airway inflammation, and remodeling. Treatment with capsazepine or TRPV1 siRNA reduced AHR to methacholine and airway inflammation. Type 2 T helper (Th2) cytokines (interleukin [IL]-4, IL-5, and IL-13) were reduced and epithelial cell-derived cytokines (thymic stromal lymphopoietin [TSLP], IL-33, and IL-25), which regulate Th2 cytokine-associated inflammation, were also reduced. Airway remodeling characterized by goblet cell hyperplasia, increased α-smooth muscle action, and collagen deposition was also alleviated by both treatments.

Conclusions: Treatment directed at TRPV1 significantly alleviated AHR, airway inflammation, and remodeling in a chronic asthma murine model. The TRPV1 receptor can be a potential drug target for chronic bronchial asthma.
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http://dx.doi.org/10.4168/aair.2018.10.3.216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911440PMC
May 2018

Extraspinal Percutaneous Osteoplasty for the Treatment of Painful Bony Metastasis.

J Korean Med Sci 2018 Feb 19;33(8):e61. Epub 2018 Feb 19.

Department of Anesthesia and Pain Medicine, Pusan National University School of Medicine, Yangsan, Korea.

Background: Extraspinal percutaneous osteoplasties (POPs) are novel techniques for the treatment of painful bony metastasis, which is often the cause of both persistent and incidental breakthrough pain. This retrospective study explored the efficacy and complications of extraspinal POPs.

Methods: The origin of the cancer metastasis, performed POP sites, necessity of adjacent joint injections, pain and Karnofsky Performance Scale (KPS) scores, complications related to the POPs, and life expectancy were evaluated from the medical records from 2009 to 2016.

Results: A total of 47 (M/F = 28/19) patients had received 54 POPs, including costoplasty, scapuloplasty, ilioplasty, humeroplasty, ischioplasty, femoroplasty, sternoplasty, and puboplasty, in order of frequency. The most common sites for the origin of the cancer, in order of frequency, were the lung, liver, breast, colon, and kidney. All patients receiving POPs including scapuloplasty, ilioplasty, humeroplasty, and femoroplasty needed adjacent joint injections before or after the POPs. Pain due to metastatic lesions was reduced significantly immediately after the POPs and the reduction was sustained until the end of their lives. The median KPS was increased from 35.4% to 67.7% immediately after the POPs. There were no complications related to the procedures. The mean life expectancy after performing the POPs, for 35 patients which died afterwards, was 99.3 days, ranging from 1 to 767 days.

Conclusion: Even though pain in the isolated POP sites may be difficult to measure due to overlapping systemic pain, the POPs provided immediate local pain relief, and the patients showed better physical performance without procedure-related complications.
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http://dx.doi.org/10.3346/jkms.2018.33.e61DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809751PMC
February 2018

Risk factors for the discontinuation of roflumilast in patients with chronic obstructive pulmonary disease.

Int J Chron Obstruct Pulmon Dis 2017 4;12:3449-3456. Epub 2017 Dec 4.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul.

Introduction: Roflumilast is a phosphodiesterase-4 inhibitor, which can decrease exacerbation in patients with chronic obstructive pulmonary disease (COPD). However, adverse effects are a major barrier to medication use, and little is known regarding the risk factors for discontinuation of roflumilast in COPD patients.

Method: A search of the clinical databases identified all patients who were prescribed roflumilast between December 2012 and April 2015 in the four hospitals of The Catholic University of Korea, Korea. The study subjects were limited to patients who had taken 500 μg of roflumilast. We studied the factors associated with drug discontinuation and drug adverse events by univariate and multivariate analyses.

Results: Among 154 eligible patients, 54 (35.1%) discontinued their roflumilast prescription. Most patients were elderly, male, current or former smokers, and had moderate-to-severe airflow limitation. Low-body mass index (BMI) patients were more likely to undergo drug discontinuation (1-unit decrease in BMI: odds ratio [OR] =1.165, =0.006; BMI <23 kg/m: OR =2.960, =0.004). Fifty-five patients (35.7%) had adverse events. Loss of appetite, diarrhea, nausea, headache, and weight loss were the most frequent adverse events. Low-BMI patients were more likely to experience adverse events (1-unit decrease in BMI: OR =1.151, =0.010; BMI <23 kg/m: OR =2.644, =0.009).

Conclusions: The patient discontinuation and adverse events rates in this study were higher than in previous randomized controlled studies. Discontinuation of roflumilast in ethnic Koreans is more likely to occur in low-BMI patients. In a clinical setting, low-BMI patients can more easily discontinue roflumilast; clinicians should, therefore, provide greater care for these patients.
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http://dx.doi.org/10.2147/COPD.S143967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720347PMC
September 2018

Adding Intra-Articular Growth Hormone to Platelet Rich Plasma under Ultrasound Guidance in Knee Osteoarthritis: A Comparative Double-Blind Clinical Trial.

Anesth Pain Med 2016 Dec 19;6(6):e41719. Epub 2016 Oct 19.

Department of Anesthesiology and Pain Medicine, Pusan National University, Korea.

Introduction: Intra-articular injections of platelet rich plasma (PRP) for the treatment of knee osteoarthritis have been shown to reduce pain and improve joint function. The aim of this study is to examine the joint function by adding intra-articular growth hormone to platelet rich plasma. This study was performed on the individuals with knee osteoarthritis and under ultrasound guidance.

Methods: Fifty four patients who were scheduled for ultra-sound guided intra-articular injection were enrolled in the study. The patients were randomly allocated to groups P (platelet rich plasma) and PS (platelet rich plasma and Somatropin). Group P and PS were injected with 5 mL of platelet rich plasma, and 4 IU growth hormone (Somatropin) added to platelet rich plasma, respectively. Intra-articular injection was performed in two steps; the onset of study and one month after. Knee joint function based on Western Ontario and McMaster osteoarthritis index (WOMAC) score at the baseline, 1 and 2 month later, and complications were evaluated.

Results: WOMAC score in both groups has been significantly reduced after injections (P = 0.030). WOMAC score reduction in group PS in first month was significantly higher than group P, but in second month 2, the difference between two groups was not significant (P = 0.235). No complication was observed.

Conclusions: These results showed that adding growth hormone to platelet rich plasma for intra-articular injection improved function of the osteoarthritic knee joint in short period of time.
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http://dx.doi.org/10.5812/aapm.41719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560632PMC
December 2016

Percutaneous Endoscopic Debridement and Drainage with Four Different Approach Methods for the Treatment of Spinal Infection.

Pain Physician 2017 09;20(6):E933-E940

Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea.

Background: The incidence of spinal infection seems to be increasing in recent years. Percutaneous endoscopic debridement and drainage (PEDD) has become an effective alternative to extensive open surgery.

Objective: This study reviewed the charter of patients who received PEDD using 4 different approach methods to evaluate the clinical results.

Study Design: An Institutional Review Board (IRB)-approved retrospective chart review.

Setting: University hospital inpatient referred to our pain clinic.

Methods: A retrospective patient chart analysis of PEDD procedures in spinal infections over a 7-year period was done for the evaluation of structural location, symptoms and signs, etiologic agents, and outcomes.

Results: Seventeen patients (11 men and 6 women, mean age 70.4 ± 11.1 years) with spinal infections received PEDD. According to the structural localization of the spinal infections, 6 cases of spondylodiscitis alone, 5 cases of spondylodiscitis with a psoas abscess, one case of spondylodiscitis with an epidural abscess, 4 cases of spondylodiscitis with epidural and psoas abscesses, and one case of spondylodiscitis with a facet joint abscess were found. All patients had preoperative symptoms of unremitting backache and febrile sensation, and signs of paravertebral muscle tenderness and limitation of spine motion. The most common etiologic bacteria were Staphylococcus aureus. Most patients (14/17) improved; the 2 failed patients received a second PEDD after recurrence, and the other received open surgery without re-PEDD. Both the numeric rating scale and Oswestry disability index scores were significantly reduced after PEDD. No complications related to PEDD were found.

Limitation: This study is limited by its retrospective design.

Conclusions: PEDD using 4 different routes brought immediate pain relief and reduced disability in treating spinal infections, especially in elderly patients with comorbid underlying disorders.Key words: Percutaneous discectomy, psoas abscess, spinal epidural abscess, spondylodiscitis, surgical endoscopy.
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September 2017

Fabrication of newspaper-based potentiometric platforms for flexible and disposable ion sensors.

J Colloid Interface Sci 2017 Dec 12;508:167-173. Epub 2017 Aug 12.

Department of Chemical Engineering, Kangwon National University, Samcheok 25913, Republic of Korea. Electronic address:

Paper-based materials have attracted a great deal of attention in sensor applications because they are readily available, biodegradable, inexpensive, and mechanically flexible. Although paper-based sensors have been developed, but important obstacles remian, which include the retention of chemical and mechanical stabilities when paper is wetted. Herein, we develop a simple and scalable process for fabrication of newspaper-based platforms by coating of parylene C and patterning of metal layers. As-prepared parylene C-coated newspaper (PC-paper) provides low-cost, disposable, and mechanically and chemically stable electrochemical platforms for the development of potentiometric ion sensors for the detection of electrolyte cations, such as, H and K. The pH and K sensors produced show near ideal Nernstian sensitivity, good repeatability, good ion selectivity, and low potential drift. These disposable, flexible ion sensors based on PC-paper platforms could provide new opportunities for the development of point-of-care testing sensors, for diagnostics, healthcare, and environment testing.
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http://dx.doi.org/10.1016/j.jcis.2017.08.036DOI Listing
December 2017

Earlier treatment improves the chances of complete relief from postherpetic neuralgia.

Korean J Pain 2017 Jul 30;30(3):214-219. Epub 2017 Jun 30.

Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea.

Background: As herpes zoster progresses via postherpetic neuralgia (PHN) to well-established PHN, it presents its recalcitrant nature to the treatment. At this point, the well-established PHN is fixed as a non-treatable, but manageable chronic painful neuropathic disorder. This study evaluated the incidence of complete relief from PHN according to PHN duration at their first visit, and the other factors influencing it.

Methods: A retrospective chart review was performed on patients with PHN at a university-based pain clinic over 7 years. The responders were defined as patients who had complete relief from pain after 1 year of active treatment. Age, sex, PHN duration at their first visit, dermatomal distribution, and underlying disorders were compared in the responder and non-responder groups. Responders were also compared according to these factors.

Results: Among 117 PHN patients (M/F = 48/69), 35 patients (29.9%) had complete relief from PHN. Mean ages were 64.3 ± 10.6 and 66.9 ± 10.7 years, numbers of male to female patients were 11/24 and 37/45, and mean durations of PHN at their first visit were 8.5 ± 6.3 and 15.3 ± 10.7 months in the responder and non- responder groups, respectively. In addition, PHN patients who visited the clinic before 9 months showed a better result. Dermatomal distribution and underlying disorders did not show significant differences.

Conclusions: Almost 30% of PHN patients received complete relief. Those who sought treatment in a pain clinic before 9 months received a better result.
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http://dx.doi.org/10.3344/kjp.2017.30.3.214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5532529PMC
July 2017

Surface-Modified Mesh Filter for Direct Nucleic Acid Extraction and its Application to Gene Expression Analysis.

Adv Healthc Mater 2017 Oct 17;6(20). Epub 2017 Jul 17.

Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.

Rapid and convenient isolation of nucleic acids (NAs) from cell lysate plays a key role for onsite gene expression analysis. Here, this study achieves one-step and efficient capture of NA directly from cell lysate by developing a cationic surface-modified mesh filter (SMF). By depositing cationic polymer via vapor-phase deposition process, strong charge interaction is introduced on the surface of the SMF to capture the negatively charged NAs. The NA capturing capability of SMF is confirmed by X-ray photoelectron spectroscopy, fluorescent microscopy, and zeta potential measurement. In addition, the genomic DNAs of Escherichia Coli O157:H7 can be extracted by the SMF from artificially infected food, and fluorescent signal is observed on the surface of SMF after amplification of target gene. The proposed SMF is able to provide a more simplified, convenient, and fast extraction method and can be applied to the fields of food safety testing, clinical diagnosis, or environmental pollutant monitoring.
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http://dx.doi.org/10.1002/adhm.201700642DOI Listing
October 2017

Epidural Dexamethasone Influences Postoperative Analgesia after Major Abdominal Surgery.

Pain Physician 2017 05;20(4):261-269

Yeungnam University School of Medicine and College of Medicine, Korea.

Background: Epidurally administered dexamethasone might reduce postoperative pain. However, the effect of epidural administration of dexamethasone on postoperative epidural analgesia in major abdominal surgery has been doubtful.

Objectives: To investigate the effects and optimal dose of epidural dexamethasone on pain after major abdominal surgery.

Study Design: A prospective randomized, double-blind study.

Setting: University hospital.

Methods: One hundred twenty ASA physical status I and II men, scheduled for gastrectomy, were enrolled. Patients were randomly assigned to receive one of 3 treatment regimens (n = 40 in each group): dexamethasone 5 mg (1 mL) with normal saline (1 mL) (group D) or dexamethasone 10 mg (2 mL) (group E) or 2 mL of normal saline (group C) mixed with 8 mL of 0.375% ropivacaine as a loading dose. After the surgery, 0.2% ropivacaine - fentanyl 4 ?g/mL was epidurally administered for analgesia. The infusion was set to deliver 4 mL/hr of the PCEA solution, with a bolus of 2 mL per demand and 15 minutes lockout time. The infused volume of PCEA, intensity of postoperative pain using visual analogue scale (VAS) during rest and coughing, incidence of postoperative nausea and vomiting (PONV), usage of rescue analgesia and rescue antiemetic, and side effects such as respiratory depression, urinary retention, and pruritus were recorded at 2, 6, 12, 24, and 48 hours after the end of surgery.

Results: The resting and effort VAS was significantly lower in group E compared to group C at every time point through the study period. On the contrary, only the resting VAS in group D was lower at 2 hours and 6 hours after surgery. Total fentanyl consumption of group E was significantly lower compared to other groups. There was no difference in adverse effect such as hypotension, bradycardia, PONV, pruritis, and urinary retention among groups.

Limitations: Use of epidural PCA with basal rate might interrupt an accurate comparison of dexamethasone effect. Hyperglycemia and adrenal suppression were not evaluated.

Conclusions: Epidural dexamethasone was effective for reducing postoperative pain. Especially, an epidural dexamethasone dose of 10 mg was more effective than a lower dose in patients undergoing gastrectomy which was associated with moderate to severe postoperative pain.
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May 2017

Can denosumab be a substitute, competitor, or complement to bisphosphonates?

Korean J Pain 2017 Apr 31;30(2):86-92. Epub 2017 Mar 31.

Department of Anesthesia and Pain Medicine, School of Medicine, Pusan National University, Yangsan, Korea.

Osteoblasts, originating from mesenchymal cells, make the receptor activator of the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to control differentiation of activated osteoclasts, originating from hematopoietic stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature osteoclasts, bone resorption increases. On the contrary, when OPG binds to the RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL resulting in inhibition of osteoclastogenesis and reduction of bone resorption. Bisphosphonates (BPs), which bind to the bone mineral and occupy the site of resorption performed by activated osteoclasts, are still the drugs of choice to prevent and treat osteoporosis. The merits of denosumab are reversibility targeting the RANKL, lack of adverse gastrointestinal events, improved adherence due to convenient biannual subcutaneous administration, and potential use with impaired renal function. The known adverse reactions are musculoskeletal pain, increased infections with adverse dermatologic reactions, osteonecrosis of the jaw, hypersensitivity reaction, and hypocalcemia. Treatment with 60 mg of denosumab reduces the bone resorption marker, serum type 1 C-telopeptide, by 3 days, with maximum reduction occurring by 1 month. The mean time to maximum denosumab concentration is 10 days with a mean half-life of 25.4 days. In conclusion, the convenient biannual subcutaneous administration of 60 mg of denosumab can be considered as a first-line treatment for osteoporosis in cases of low compliance with BPs due to gastrointestinal trouble and impaired renal function.
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http://dx.doi.org/10.3344/kjp.2017.30.2.86DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5392661PMC
April 2017

Prediction of endotracheal tube size for pediatric patients from the epiphysis diameter of radius.

Korean J Anesthesiol 2017 Feb 25;70(1):52-57. Epub 2016 Oct 25.

Department of Anesthesia and Pain Medicine, Pusan National University Yangsan Hospital and School of Medicine, Yangsan, Korea.

Background: Using a too big or a too small size of an endotracheal tube in pediatric patients would result in tracheal injury or insufficient ventilation. Determining the appropriate endotracheal tube size is important because using an inappropriate size can cause complications. This study was performed to predict the appropriate endotracheal tube size by measuring the transverse diameter of the epiphysis of the distal radius under the assumption that the growth rates of cartilages in the entire body are close to each other.

Methods: Fifty-eight children aged 3 to 10 years who required general anesthesia were intubated with an uncuffed endotracheal tube. The tube size was considered to be appropriate when leaks occurred at inspiratory peak pressures between 10 to 25 mmHg. The transverse diameters of the epiphysis were measured with an ultra-sonogram at the distal radius and the proximal phalanx of the third finger and the fifth finger. Correlations and prediction probabilities of measurements were evaluated. The number needed to harm (NNH), which indicates the number of patients who need to be intubated for one patient who needs tube exchange, was investigated.

Results: The Spearman's correlation coefficient between the endotracheal tube size and the epiphysis of the distal radius was 0.814, which was the biggest coefficient. For epiphysis of the proximal phalanx of the third finger and the fifth finger, the correlation coefficient was 0.704 and 0.701, respectively. If the Cole's formula was applied for selection of the tube size, the NNH would be 7.

Conclusions: The appropriate endotracheal tube size could be predicted by means of the epiphyseal transverse diameter of the distal radius rather than the circumference measurements of the phalanx.
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http://dx.doi.org/10.4097/kjae.2017.70.1.52DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5296388PMC
February 2017
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