Purpose: The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial. Materials and Methods: Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×109 or 4×109 cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life. Results: Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×109 cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001). Conclusion Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by recurrent abscesses, nodules, and fistulous tracts. Recently, novel staging systems, including sonographic scoring system of hidradenitis suppurativa (SOS-HS), have been widely introduced in HS. Objective: To assess the efficacy of SOS-HS compared with Hurley staging and modified sartorius scoring (MSS) system and determine the necessity of ultrasound evaluation. Methods: A radiologist performed an ultrasound evaluation, and three dermatologists reviewed the images and videos. Clinical characteristics, including staging and demographic data, were recorded by three dermatologists. The correlation of each staging system and the significance of vascularity (Doppler mode) and lesion depth on sonography were statistically analyzed. Results: Among the 46 patients, 34.8% were classified as stage 1 and 3, and 30.4% were classified as stage 2 in the SOS-HS system, which was statistically higher than the Hurley staging (p＜0.0005). MSS score increased according to the SOS-HS stages (p＜0.0005, p=0.001). Vascularity and depth of involvement also increased with SOS-HS and Hurley staging. Conclusion Sonographic examination can be applied in HS severity assessment and documentation of the clinical characteristics of each lesion in detail. Special tools, such as Doppler mode and depth assessment, can also be useful in HS evaluation.

Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterized by recurrent abscesses, nodules, and fistulous tracts. Recently, novel staging systems, including sonographic scoring system of hidradenitis suppurativa (SOS-HS), have been widely introduced in HS. Objective: To assess the efficacy of SOS-HS compared with Hurley staging and modified sartorius scoring (MSS) system and determine the necessity of ultrasound evaluation. Methods: A radiologist performed an ultrasound evaluation, and three dermatologists reviewed the images and videos. Clinical characteristics, including staging and demographic data, were recorded by three dermatologists. The correlation of each staging system and the significance of vascularity (Doppler mode) and lesion depth on sonography were statistically analyzed. Results: Among the 46 patients, 34.8% were classified as stage 1 and 3, and 30.4% were classified as stage 2 in the SOS-HS system, which was statistically higher than the Hurley staging (p＜0.0005). MSS score increased according to the SOS-HS stages (p＜0.0005, p=0.001). Vascularity and depth of involvement also increased with SOS-HS and Hurley staging. Conclusion Sonographic examination can be applied in HS severity assessment and documentation of the clinical characteristics of each lesion in detail. Special tools, such as Doppler mode and depth assessment, can also be useful in HS evaluation.

Polymorphic ventricular tachycardia (PVT) is a fatal arrhythmia that can occur during the treadmill test. This report documents an instance of PVT by the R-on-T phenomenon during an exercise stress test in a 61-year-old male with stable angina pectoris. The subject performed the treadmill test for 581 seconds, and stopped after reaching 115% of the target heart rate. Ischemic ST changes were observed in leads II, III, aVF, and V3-V6 from stage 3. Premature ventricular complexes were noted during the recovery period, with an occurrence of pulseless PVT, reflective of the R-on-T phenomenon. Spontaneous circulation was resumed after unsynchronized cardioversion at 200 J and 2 minutes of cardiopulmonary resuscitation. Emergency coronary angiography revealed 95% stenosis of the proximal right coronary artery, which was fully dilated after percutaneous coronary intervention with a drug-eluting stent. The patient was discharged without any neurologic sequelae.

Background: In this study, we sought to evaluate whether systemic propentofylline (PPF) has antiallodynic effects in a rat model of postoperative pain, and to assess the mechanism involved. Methods: After plantar incision, rats were intraperitoneally injected with various doses of PPF to evaluate its antiallodynic effect. To investigate the involved mechanism, rats were intraperitoneally injected with yohimbine, dexmedetomidine, prazosin, naloxone, atropine or mecamylamine, following the incision of the rat hind paws, and then PPF was administered intraperitoneally. The mechanical withdrawal threshold (MWT) was evaluated using von Frey filaments at various time points and serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were measured to determine the inflammatory response level. Results: MWT was significantly increased after intraperitoneal injection of 30 mg/ kg of PPF when compared with the control group. Injection of PPF and yohimbine, atropine or mecamylamine showed significant decreases in the MWT, while injection of PPF and dexmedetomidine showed a significant increase. Systemic administration of PPF inhibited the post-incisional increase in serum level of TNF-α and IL-1β. Conclusions Systemic administration of PPF following surgery presented antiallodynic effects in a rat model of postoperative pain. The antiallodynic effects against mechanical allodynia could be mediated by α-adrenergic and cholinergic receptors.

“Clinical Practice Guideline for Stroke Rehabilitation in Korea 2016” is the 3rd edition of clinical practice guideline (CPG) for stroke rehabilitation in Korea, which updates the 2nd edition published in 2014. Forty-two specialists in stroke rehabilitation from 21 universities and 4 rehabilitation hospitals and 4 consultants participated in this update. The purpose of this CPG is to provide optimum practical guidelines for stroke rehabilitation teams to make a decision when they manage stroke patients and ultimately, to help stroke patients obtain maximal functional recovery and return to the society. The recent two CPGs from Canada (2015) and USA (2016) and articles that were published following the 2nd edition were used to develop this 3rd edition of CPG for stroke rehabilitation in Korea. The chosen articles' level of evidence and grade of recommendation were decided by the criteria of Scotland (2010) and the formal consensus was derived by the nominal group technique. The levels of evidence range from 1++ to 4 and the grades of recommendation range from A to D. Good Practice Point was recommended as best practice based on the clinical experience of the guideline developmental group. The draft of the developed CPG was reviewed by the experts group in the public hearings and then revised. “Clinical Practice Guideline for Stroke Rehabilitation in Korea 2016” consists of ‘Chapter 1; Introduction of Stroke Rehabilitation’, ‘Chapter 2; Rehabilitation for Stroke Syndrome, ‘Chapter 3; Rehabilitation for Returning to the Society’, and ‘Chapter 4; Advanced Technique for Stroke Rehabilitation’. “Clinical Practice Guideline for Stroke Rehabilitation in Korea 2016” will provide direction and standardization for acute, subacute and chronic stroke rehabilitation in Korea.
Canada ; Consensus ; Consultants ; Humans ; Korea* ; Practice Guidelines as Topic ; Rehabilitation* ; Scotland ; Specialization ; Stroke*

BACKGROUND: The recently known analgesic action mechanisms of nefopam (NFP) are similar to those of anticonvulsants and antidepressants in neuropathic pain treatment. It is difficult to prescribe high doses of oral neuropathic drugs without titration due to adverse effects. Unfortunately, there are few available intravenous analgesics for the immediate management of acute flare-ups of the chronic neuropathic pain. The aim of this study was to determine the additional analgesic effects for neuropathic pain of NFP and its adverse effects during the titration of oral medications for neuropathic pain among inpatients with postherpetic neuralgia (PHN). METHODS: Eighty inpatients with PHN were randomly divided into either the NFP or normal saline (NS) groups. Each patient received a 3-day intravenous continuous infusion of either NFP with a consecutive dose reduction of 60, 40, and 20 mg/d, or NS simultaneously while dose titrations of oral medications for neuropathic pain gradually increased every 3 days. The efficacy of additional NFP was evaluated by using the neuropathic pain symptom inventory (NPSI) score for 12 days. Adverse effects were also recorded. RESULTS: The median NPSI score was significantly lower in the NFP group from days 1 to 6 of hospitalization. The representative alleviating symptoms of pain after using NFP were both spontaneous and evoked neuropathic pain. Reported common adverse effects were nausea, dizziness, and somnolence, in order of frequency. CONCLUSIONS: An intravenous continuous infusion of NFP reduces spontaneous and evoked neuropathic pain with tolerable adverse effects during the titration of oral medications in inpatients with PHN.
Analgesics ; Anticonvulsants ; Antidepressive Agents ; Dizziness ; Hospitalization ; Humans ; Inpatients ; Nausea ; Nefopam* ; Neuralgia ; Neuralgia, Postherpetic*

A secondary aortoenteric fistula (AEF) is a direct communication between the gastrointestinal tract and the aorta in a patient who has undergone major surgery on the aorta, often an aorta graft operation. We experienced a patient who had undergone graft interposition for abdominal aortic aneurysm and was admitted due to three episodes of hematemesis and following hamatochezia. Gastroscopy, colonoscopy, and radioactive iodine scan failed to identify the bleeding site in the patient. He was diagnosed with AEF by double balloon enteroscopy and recovered after surgical intervention.
Aorta ; Aortic Aneurysm, Abdominal ; Colonoscopy ; Double-Balloon Enteroscopy ; Fistula ; Gastrointestinal Tract ; Gastroscopy ; Hematemesis ; Hemorrhage ; Humans ; Iodine ; Lymphokines ; Transplants

PURPOSE: Features of epidermal growth factor receptor (EGFR) expression in osteosarcoma and in vitro efficacies of EGFR inhibitors against osteosarcoma cells were evaluated. MATERIALS AND METHODS: Thirty biopsy samples of osteosarcoma patients were retrospectively analyzed for EGFR protein expression by immunohistochemistry. Relationships between EGFR expression and clinicopathologic characteristics and treatment outcomes were evaluated. Four osteosarcoma cell lines were analyzed for EGFR and p-EGFR expression by western blotting. Efficacies of gefitinib and BIBW2992 on osteosarcoma cells were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tyrosine kinase domains in exons 18 to 21 were sequenced and gene expression analyses of EGFR and PTEN were performed in four osteosarcoma cell lines. RESULTS: EGFR protein was expressed in 27 (90%) samples (6 low, 12 intermediate, 9 high) and in three cell lines. Intermediate or high staining for EGFR was related to a tumor volume<150 mL (p<0.001) and histologic subtype other than osteoblastic type (p=0.03). However, EGFR expression was not associated with histologic response to preoperative chemotherapy or survival. Gefitinib and BIBW 2992 did not have any significant inhibitory effect on cell viabilities. DNA sequencing analysis revealed three osteosarcoma cell lines have single base changes at codon 2361 of exon 20 (G to A), without affecting translation results. Furthermore, no mutation was found to be associated with constitutive EGFR activation. CONCLUSION: In the present study, gefitinib and BIBW2992 were not effective against osteosarcoma cells. However, as osteosarcoma cells express EGFR, further studies are necessary to explore the potential of other therapeutic agents targeting EGFR.
Biopsy ; Blotting, Western ; Cell Line ; Cell Survival ; Codon ; Epidermal Growth Factor ; Exons ; Gene Expression ; Humans ; Immunohistochemistry ; Osteoblasts ; Osteosarcoma ; Protein-Tyrosine Kinases ; Quinazolines ; Receptor, Epidermal Growth Factor ; Retrospective Studies ; Sequence Analysis, DNA ; Tetrazolium Salts ; Thiazoles

BACKGROUND/AIMS: The meaning of specialized intestinal metaplasia (SIM) in the diagnosis of Barrett's esophagus (BE) is not clear. This study was designed to determine the clinical significance of SIM in the diagnosis of Barrett's esophagus. MATERIALS AND METHODS: Biopsies were taken from 601 subjects with endoscopically suspected columnar-lined esophagus. Under light microscopy with Alcian-blue stain, SIM was identified. Demographic characteristics, gastroesophageal (GE) reflux symptoms and endoscopic findings were compared between the SIM-present group and the SIM-absent group. RESULTS: Among 601 subjects, 184 (30.6%) were confirmed by pathology to have SIM. Age over 40 years (P<0.001) and a medication history of proton pump inhibitor or H2 blocker were found more frequently in the SIM-present group (P=0.01) than in the SIM-absent group. Any of 7 GE reflux symptoms (heartburn, acid regurgitation, chest pain, hoarseness, globus sensation, cough and epigastric soreness) were more frequent in the SIM-present group than SIM-absent group (P<0.001). Specifically, heartburn, chest pain and cough were significantly more common in the SIM-present group. There was no clinically significant difference associated with endoscopic findings or other clinical characteristics. CONCLUSIONS: When subjects with endoscopically suspected BE are analyzed based on the presence or absence of SIM, the SIM-present group was significantly associated with GE reflux symptoms suggestive of frequent GE reflux. However, the presence of SIM did not correlate with endoscopic findings.
Barrett Esophagus ; Biopsy ; Chest Pain ; Cough ; Esophagus ; Gastroesophageal Reflux ; Heartburn ; Hoarseness ; Light ; Metaplasia ; Microscopy ; Prospective Studies ; Proton Pumps ; Sensation