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.
Analgesia ; Analgesics, Opioid ; Animals ; Bias (Epidemiology) ; Drug-Related Side Effects and Adverse Reactions ; GTP-Binding Proteins ; Intracellular Signaling Peptides and Proteins ; Ligands ; Mice ; Mice, Knockout ; Nausea ; Patient Safety ; Pharmacokinetics ; Receptors, Opioid ; Receptors, Opioid, mu ; Respiratory Insufficiency ; Vomiting

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.
Breakthrough Pain ; Breast ; Cementoplasty ; Colon ; Early Ambulation ; Humans ; Joints ; Karnofsky Performance Status ; Kidney ; Life Expectancy ; Liver ; Lung ; Medical Records ; Neoplasm Metastasis ; Retrospective Studies

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.
Antibodies, Monoclonal ; Biomarkers ; Bone Density ; Bone Resorption ; Compliance ; Denosumab* ; Diphosphonates* ; Half-Life ; Hematopoietic Stem Cells ; Hypersensitivity ; Hypocalcemia ; Jaw ; Miners ; Musculoskeletal Pain ; NF-kappa B ; Osteoblasts ; Osteoclasts ; Osteonecrosis ; Osteoporosis ; Osteoprotegerin ; RANK Ligand

BACKGROUND AND OBJECTIVES: Laryngotracheal stenosis (LTS) in burned patients with inhalation injury have features distinct from other stenosis after intubation or tracheotomy. However, the risk factors for LTS in burned patients with inhalation injury have not been thoroughly assessed. The aim of this study is to identify the risk factors for and evaluate the pattern of LTS in burned patients with inhalation injury. SUBJECTS AND METHOD: From May 2005 to April 2007, 227 burned patients with inhalation injury treated at the Hangang Sacred Heart Hospital, Hallym University Medical Center were investigated retrospectively. The risk factors analyzed for LTS in burned patients with inhalation injury were gender, age, duration of intubation, size of the endotracheal tube, previous tracheotomy, number of intubations, severity of inhalation injury. RESULTS: Among 81 patients who survived and could be followed up until the study period, 10 (12%) patients developed LTS. The stenosis involved the subglottis.cervical trachea (5), subglottis.cervical tracheal and glottis (1), glottis (4). According to Myer-Cotton classification, there were 6 (60%) patients with grade III, IV stenoses on subglottis.cervical trachea. The number of intubations and previous tracheotomy were found to be risk factors for the development of LTS in burned patients with inhalation injury. CONCLUSION: LTS by inhalation injury is usually shown on web at the anterior and posterior glottic areas or circumferential narrowing of the subglottis. Repeated endotracheal intubations and previous tracheotomy in patients with inhalation injury may increase the prevalence of LTS.
Academic Medical Centers ; Burns ; Burns, Inhalation ; Constriction, Pathologic ; Glottis ; Heart ; Humans ; Inhalation ; Intubation ; Intubation, Intratracheal ; Laryngostenosis ; Prevalence ; Retrospective Studies ; Risk Factors ; Trachea ; Tracheal Stenosis ; Tracheotomy

OBJECTIVES: To compare the velopharyngeal function, swallowing and speech of the conventional and modified radial forearm free flap (RFFF) for soft palate reconstruction. METHODS: Retrospective clinical study. Twenty-eight patients who underwent oropharyngeal reconstruction with RFFF were divided into two groups: 10 patients had conventional folded RFFF and 18 patients underwent modified method. RESULTS: The average speech intelligibility score in modified RFFF group was 8.0+/-2.4, and 6.2+/-2.2 in conventional RFFF group (P<0.05). The nasalance was 27.4+/-7.8% in modified group and 38.6+/-2.7% in conventional group during no nasal passage reading and 43.6+/-7.3% in modified group, 55.2+/-7.6% in conventional group during high nasal passage reading (P<0.05). The subjective swallowing functional score was 2.8 in modified group and 2.1 in conventional group. CONCLUSION: The speech assessment and nasalance demonstrate a more favorable outcome in modified group than conventional group.
Deglutition ; Forearm ; Free Tissue Flaps ; Humans ; Oropharyngeal Neoplasms ; Palate, Soft ; Retrospective Studies ; Speech Intelligibility

BACKGROUND AND OBJECTIVES: Inhalation injuries can produce a wide spectrum of negative clinical effects. Respiratory failure remains one of the leading causes of death in burned patients with inhalation injury. Despite advances in understanding of inhalation injury, few studies have focused on histopathologic findings of tracheal mucosa. The purpose of this study is to investigate histopathologic changes of tracheal mucosa in burned patients with inhalation injury. SUBJECTS AND METHOD: Tracheotomy was performed on 31 patients who was admitted to the Hospital center from May 2005 to March 2006. Thirty-one patients were divided into two groups : patients with inhalation injury (group I)(n=16), patients without inhalation injury (group II)(n=15). Tracheal mucosa were taken out during the tracheotomy. The tracheal mucosa were read blindly by one pathologist. RESULTS: Histopathologic examination showed the following finding in the tracheal mucosa of all patients in the group I : epithelial ulceration. Different findings were observed in the group I as time passed by after inhalation injury, such as interstitial edema, inflammatory cell infiltration, capillary dilatation, and increased fibrosis. No abnormal findings were observed in the tracheal mucosa in the group II. CONCLUSION: Inhalation injuries cause histopathologic damages to tracheal mucosa. The different histopathologic findings of tracheal mucosa that take place in time following inhalation injuries suggest to process an inflammatory reaction. The study in related to clinical features should be needed due to tracheal mucosa injury may produce respiratory complications.
Burns* ; Burns, Inhalation ; Capillaries ; Cause of Death ; Dilatation ; Edema ; Fibrosis ; Humans ; Inhalation* ; Mucous Membrane* ; Respiratory Insufficiency ; Trachea ; Tracheotomy ; Ulcer

BACKGROUND AND OBJECTIVES: Pharyngocutaneous fistula after total laryngectomy is one of the most common complication in the immediate postoperative period. The objective of this study is to evaluate the variable predisposing factors after total laryngectomy and to investigate the management of pharyngocutaneous fistula. SUBJECTS AND METHOD: One hundred fifty cases who had been performed total laryngectomy were investigated retrospectively. Fifteen of 150 cases (10.0%) developed pharyngocutaneous fistula after total laryngectomy. We analyzed clinical parameters such as age, sex, smoking, alcohol intake, DM (diabetes mellitus), hypertension, liver disease, postoperative hemoglobin, albumin etc. RESULTS: Smoking, DM, hypertension, postoperative hemoglobin, postoperative albumin were significant factors associated with pharyngocutaneous fistula. Nine patients were managed with conservative treatment and six patients underwent surgical reconstruction by using pectoralis major myocutaneous flap. The average duration of oral feeding was 30 postoperative days in conservative treatment group and 83 postoperative days in surgical intervention group. CONCLUSION: Pharyngocutaneous fistula may be preventable by correcting the predisposing factors. We must consider the initial size of fistula and the response of conservative treatment to determine methodology and timing of surgical management.
Causality ; Fistula* ; Humans ; Hypertension ; Laryngectomy* ; Liver Diseases ; Myocutaneous Flap ; Postoperative Period ; Retrospective Studies ; Smoke ; Smoking

BACKGROUND AND OBJECTIVES: The hepatocyte growth factor (HGF)/c-Met signal pathway may play various roles in carcinogenesis of several organs. However, studies about this pathway in head and neck cancers, especially oral cavity and oropharyngeal squamous cell carcinoma (SCC), are very rare. Our objectives are to evaluate the relationship between the mRNA and protein expression of HGF and c-met genes in oral cavity and oropharyngeal carcinomas. SUBJECTS AND METHOD: In this study, we examined the mRNA expression of HGF and c-Met by means of the immunohistochemistry (IHC) method and reverse transcription polymerase chain reaction (RT-PCR) in 40 cases of surgically resected oral cavity and oropharyngeal SCC and 10 cases of low grade dysplasia. RESULTS: Using RT-PCR, HGF mRNA amplification was detected in 67.5% and 10% of carcinoma and dysplasia. c-Met mRNA over-expression was detected in 57.5% and 20% of carcinoma and dysplasia. Using IHC, HGF and c-Met protein over-expression was detected in 55% and 62.5% in carcinoma, but not detected in dysplasia. CONCLUSION: These results suggest that HGF/c-Met signal pathway may be associated with the development of oral cavity and oropharyngeal SCC.
Carcinogenesis ; Carcinoma, Squamous Cell* ; Gene Expression* ; Head ; Hepatocyte Growth Factor* ; Hepatocytes* ; Immunohistochemistry ; Mouth* ; Neck ; Oropharynx ; Polymerase Chain Reaction ; Reverse Transcription ; RNA, Messenger ; Signal Transduction

BACKGROUND AND OBJECTIVES: Galectin-3 is a beta-galactoside binding protein, of which the major function is not fully elucidated in malignant tumor. However, galectin-3 is expressed in epithelial cells and contributes to the progression of cancer. Although galectin-3 is expressed in a variety of tissues and plays important roles in malignant transformation or tumor progression, the study on its expression related to clinicopathological parameters in thyroid tumor is rare. So, the present study aims to find out the clinical significance of galectin-3 in thyroid tumor. SUBJECTS AND METHOD: We assessed mRNA and protein expressions of the galectin-3 gene by means of the RT-PCR method and immunohistochemical staining in 100 cases of thyroid tumors (50 papillary carcinomas, 10 follicular carcinomas, 20 follicular adenomas, 20 nodular hyperplasia). The expression of galectin-3 is compared with the clinical prognostic factors of thyroid papillary cancer. RESULTS: Using RT-PCR, galectin-3 mRNA was detected in 41 (82%) in papillary carcinoma, 6 (60%) in follicular carcinoma, 8 (40%) in follicular adenoma and 9 (45%) in nodular hyperplasia cases. Using immunohistochemical staining, galectin-3 protein expressions were detected in 46 (92%), 7 (70%), 3 (15%) and 1 (5%). The expressions of the galectin-3 mRNA and protein were significantly recognized in thyroid papillary carcinoma. However, the galectin-3 mRNA and protein over-expression is not significantly correlated with the clinical prognostic factors of thyroid papillary carcinoma. CONCLUSION: These results suggest that galectin-3 expression may be associated with thyroid papillary carcinoma development.
Adenoma ; Carcinoma, Papillary ; Carrier Proteins ; Epithelial Cells ; Galectin 3* ; Hyperplasia ; RNA, Messenger ; Thyroid Gland*

BACKGROUND AND OBJECTIVES: In radical neck dissection, sacrifice of the spinal accessory nerve creates a definite deficit of the shoulder function. To demonstrate the presence of motor input from the spinal accessory and the cervical plexus to the trapezius muscle, intra-operative motor nerve conduction study was performed. SUBJECTS AND METHOD: Twenty-four patients were studied on completion of the operation. In each patient, the entire length of the spinal accessory nerve, the upper cervical plexus and some cervical plexus branches running to the trapezius were preserved independently. Compound muscle action potentials were measured for each part of the trapezius muscle on stimulation of the spinal accessory, C2, C3 and C4 nerves. RESULTS: By stimulating the spinal nerve, evoked responses were obtained from all 24 patients in the upper, middle and lower trapezius. C2 contributions were seen in 2 out of 24 patients, supplying all three parts of the muscle in 0. C3 contributions were seen in 11 out of 24 patients, supplying all three parts of the muscle in 8. C4 contributions were seen in 20 out of 24 patients, supplying all three parts of the muscle in 16. CONCLUSION: The spinal accessory nerve provides the most important and consistent motor input and C2, C3 and C4 also provide motor input to the trapezius muscle. But they were not consistently present and did not innervate all three parts of the trapezius muscle. Compared with other studies, it is interesting to note that C4 gives more consistent motor input to the trapezius muscle than other cervical branches.
Accessory Nerve ; Action Potentials ; Cervical Plexus ; Humans ; Neck Dissection ; Neural Conduction ; Running ; Shoulder ; Spinal Nerves ; Superficial Back Muscles*