ABSTRACT
Sedation methods for dental treatment are increasingly explored. Recently, ketofol, which is a combination of ketamine and propofol, has been increasingly used because the advantages and disadvantages of propofol and ketamine complement each other and increase their effectiveness. In this review, we discuss the pharmacology of ketamine and propofol, use of ketofol in various clinical situations, and differences in efficacy between ketofol and other sedatives.
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The prognosis of patients with chronic phase (CP) chronic myeloid leukemia (CML) has significantly improved due to the development of potent BCR::ABL1 tyrosine kinase inhibitors (TKIs). However, approximately 15‒20% of patients ultimately experience treatment failure due to resistance or intolerance to TKI therapy. As the prognosis of patients in whom multiple TKIs fail remains poor, an optimal therapeutic approach is required to treat the condition. Asciminib, an allosteric inhibitor that targets ABL1 myristoyl pocket, has been approved by the Food and Drug Administration for use in patients with CP-CML resistant or intolerant to ≥2 prior TKIs or those with T315I mutation. In a phase 1 trial, asciminib monotherapy showed a relatively favorable safety profile and potent efficacy in patients with and without the T315I mutation. In a subsequent phase 3 trial, asciminib treatment was associated with a significantly higher major molecular response rate and lower discontinuation rate than bosutinib in patients with CP-CML for whom two previous TKIs failed. Several clinical trials are being performed in various clinical settings to evaluate the role of asciminib as a frontline treatment for newly diagnosed CP-CML, either as a single agent or in combination with other TKIs as a second-line or additive treatment to improve treatment-free or deep remission. This review summarizes the incidence, available therapies, and outcomes of patients with CP-CML who experienced treatment failure, the mechanism of action, preclinical and clinical data, and ongoing trials for asciminib.
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Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/ AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.
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Background@#Upadacitinib is an oral Janus kinase1 (JAK1)-selective inhibitor, which showed a quick and significant effect on patients with atopic dermatitis in several phase 3 clinical studies. Although, an increasing number of studies have reported data on the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis, no studies have yet been published in Korea. @*Objective@#We assessed the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis in Korean patients. @*Methods@#A total of 17 patients with atopic dermatitis who received 15 mg of oral upadacitinib everyday for 16 weeks, were included in this retrospective single-center study. Based on electronic medical records, the clinical characteristics, Eczema Area and Severity Index (EASI) score, and adverse events were investigated. @*Results@#The mean EASI score was significantly reduced at 4 weeks of upadacitinib treatment (8.81±9.00) and gradually reduced at week 8 (5.70±7.38), week 12 (4.55±6.23), and week 16 (4.58±6.74) (p＜0.001). At week 16, 61.54%, 30.77%, and 15.38% of patients achieved EASI 75, EASI 90, and EASI 100 responses, respectively. There was no statistically significant difference between EASI 75 and EASI 90 by age or gender at week 16 (p＞0.05). A total of 13 people (76.5%) had adverse events, of which acne was the most common. In all patients, the symptoms were mild and self-limited, and no patient discontinued treatment. @*Conclusion@#Upadacitinib was effective and safe for Korean patients with atopic dermatitis in real-world clinical practice.
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Background@#Inflammatory dental diseases that occur during pregnancy can cause preterm labor and/or intrauterine growth restriction. Therefore, proactive treatment of dental diseases is necessary during pregnancy. Dexmedetomidine (DEX) is a widely used sedative in the dental field, but research on the effect of DEX on pregnancy is currently insufficient. In this study, we investigated the effects of co-treatment with DEX and lipopolysaccharide (LPS) on inflammatory responses in human amnion-derived WISH cells. @*Methods@#Human amnion-derived WISH cells were treated with 0.001, 0.01, 0.1, and 1 μg/mL DEX with 1 μg/mL LPS for 24 h. Cytotoxicity of WISH cells was evaluated by 3-(4,5-)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E 2 (PGE 2 ), p38, and nuclear factor kappa B (NF-κB) was examined by western blot analysis. The mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-1β and tumor necrosis factor (TNF)-α was analyzed by real-time quantitative polymerase chain reaction. @*Results@#Co-treatment with DEX and LPS showed no cytotoxicity in the WISH cells. The mRNA expression of IL-1β and TNF-α decreased after co-treatment with DEX and LPS. DEX and LPS co-treatment decreased the protein expression of COX-2, PGE 2 , phospho-p38, and phospho-NF-κB in WISH cells. @*Conclusion@#Co-treatment with DEX and LPS suppressed the expression of COX-2 and PGE 2 , as well as pro-inflammatory cytokines such as IL-1β and TNF-α in WISH cells. In addition, the anti-inflammatory effect of DEX and LPS co-treatment was mediated by the inhibition of p38/NF-κB activation.
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Background/Aims@#Recent advances in the understanding of the pathophysiology of myeloproliferative neoplasms (MPN) were not paralleled with advances in treatment options; thus many questions regarding optimal MPN management remain unanswered. Here, we report the results of descriptive survey study of Korean MPN patients and their attending physicians. @*Methods@#A total of 105 Korean patients (myelofibrosis [MF], 39; polycythemia vera [PV], 25; essential thrombocythemia [ET], 41) and 30 physicians completed the Landmark Health Survey, then data from the survey were analyzed. @*Results@#Among the MPN-Symptom Assessment Form symptoms, the most severe symptom reported was ‘fatigue or tiredness’ in MF and ET patients and ‘itching’ in PV patients. The majority of the patients agreed that MPN reduced their quality of life (QoL). Interestingly, physicians gave higher scores regarding the impact of MPN on patient’s daily and social life compared to patients themselves. For patients, the most important treatment goal was symptom improvement regardless of MPN subtype, while for physicians the highest priority for treatment was better QoL regardless of MPN subtype. Generally, both patients and physicians were satisfied with the overall treatment/management of MPN and communications. However, many patients felt there was not enough time during the appointment for discussion, while many physicians felt they lacked effective drugs to offer to their patients. @*Conclusions@#Our study suggests there are room for better-standardized monitoring of symptoms and treatment options and those continuous efforts to bridge the gap between patients and physicians are necessary for better care of MPN patients.
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Immune thrombocytopenia (ITP) is an autoimmune condition characterized by platelet destruction through antibody-mediated mechanism. ITP is one of the manifestations of a coronavirus disease, as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several cases of ITP have been described after vaccination with two mRNA-based vaccines—BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—against SARS-CoV-2. Herein, we report a case of ITP occurring after vaccination with ChAdOx1 adenovirus vector nCoV-19 (AstraZeneca) vaccine in Korea. A 66-year-old woman presented with multiple ecchymoses on both upper and lower extremities and gingival bleeding, appearing 3 days after receiving the first dose of ChAdOx1 nCoV-19. Her laboratory results showed isolated severe thrombocytopenia without evidence of combined coagulopathy. She was diagnosed with ITP and successfully treated with high-dose dexamethasone and intravenous immunoglobulin. Clinical suspicion to identify vaccinerelated ITP is important to promptly initiate appropriate treatment.
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Behçet’s disease is a chronic inflammatory disorder involving vessels of various sizes and organs, including the skin, joints, gastrointestinal tract, lungs, and cardiovascular system. The etiology of Behçet’s disease is unclear, and clinical diagnosis is important in the absence of definitive laboratory or pathological findings diagnostic of Behçet’s disease. Cardiac involvement is rare but might present as endocarditis, myocarditis, pericarditis, or intracardiac thrombosis. This report presents a case of Behçet’s disease involving the heart in a 22-year-old man with unusual manifestations of right ventricular fibrosis and intracardiac thrombosis. Cardiac magnetic resonance imaging revealed multiple intracardiac thrombi and delayed diffuse subendocardial enhancement involving the right ventricle. No peripheral eosinophilia was detected. Endomyocardial biopsy showed mixed inflammatory cell infiltrates. Based on the patient’s clinical history of oral ulcer and arthritis, a diagnosis of Behçet’s disease was made considering the clinical, radiological, and histological findings. Intracardiac thrombi and endomyocardial fibrosis are rare manifestations of Behçet’s disease, and the diagnosis is often a clinical challenge. Early diagnosis is important for appropriate management. Behçet’s disease should be considered in the differential diagnosis of patients with intracardiac thrombosis and endomyocardial fibrosis of the right chamber.
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Objectives@#Postoperative opioid use and pain are related to postoperative delirium. This study aims to compare the incidence of delirium in patients with and without patient-controlled intravenous analgesia (PCIA) among liver transplant recipients. @*Methods@#The medical records of 253 patients who received liver transplantation (LT) from January 2010 to July 2017 in a single university hospital were retrospectively reviewed. Patients were divided into two groups: the patients who had used PCIA (P group, n = 71) and those who did not use PCIA (C group, n = 182) after LT in intensive care unit (ICU). The patient data were collected, which included demographic data, and details about perioperative management and postoperative complications. @*Results@#There was no difference in the model for end-stage liver disease (MELD) score between the two groups. Postoperative delirium occurred in 10 / 71 (14.08 %) in the P group and 26 / 182 (14.29 %) in the C group after LT, respectively (P = 0.97). After propensity score matching, no differences were observed in the incidence of delirium (P = 0.359) and the time from surgery to discharge (P = 0.26) between the two groups. @*Conclusions@#Patients with PCIA after LT exhibited no relationship with postoperative delirium. Therefore, it is necessary to actively control postoperative pain using PCIA.
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Background@#Pierre Robin sequence (PRS) patients have an increased risk of difficult intubation due to anatomical airway abnormalities, and intubation simulation with a three-dimensional (3D) printed airway model before anesthesia may facilitate safe airway management. Case: We describe the case of a 6.5-year-old boy with a history of PRS (a triad of micrognathia, glossoptosis, and airway obstruction), tracheostomy, and subglottic fibrosis who required general anesthesia. Preparation for this potentially difficult intubation included estimation of endotracheal tube size using a 3D printed airway model derived from 3D computed tomography of the airway, which enabled successful endotracheal intubation via video laryngoscopy. @*Conclusions@# If general anesthesia is necessary in patients with dysmorphic features such as PRS and there is a history of tracheal pathology, the possibility of difficult intubation should always be considered and simulation of endotracheal intubation using a 3D printed model of the airway can be helpful clinically in such situations.
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Background@#This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). @*Methods@#We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000– September 2017) at our center. @*Results@#Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34 + cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. @*Conclusion@#Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.
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This study aimed to investigate whether neurotransmitter receptors in the nervous system were also expressed in oral keratinocytes. Expressions of various neurotransmitter receptor genes in immortalized mouse oral keratinocyte (IMOK) cells were examined by reverse transcriptase polymerase chain reaction. IMOK cells expressed calcitonin gene-related peptide (CGRP) receptor subunit genes Ramp1 and Ramp3 and glutamate receptor subunit genes Grina , Gria3 , Grin1 , Grin2a , and Grin2d . Moreover, IMOK cells expressed Adrb2 and Chrna5 that encode beta 2 adrenergic receptor and cholinergic receptor nicotinic alpha 5 for sympathetic and parasympathetic neurotransmitters, respectively. The expression of Bdkrb1 and Ptger4 , which encode receptors for bradykinin and prostaglandin E2 involved in inflammatory responses, was also observed at low levels. Expressions of Ramp1 and Grina in the mouse gingival epithelium were also confirmed by immunohistochemistry. When the function of neurotransmitter receptors expressed on IMOK cells was tested by intracellular calcium response, CGRP, glutamate, and cholinergic receptors did not respond to their agonists, but the bradykinin receptor responded to bradykinin. Collectively, oral keratinocytes express several neurotransmitter receptors, suggesting the potential regulation of oral epithelial homeostasis by the nervous system.
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Objectives@#Postoperative opioid use and pain are related to postoperative delirium. This study aims to compare the incidence of delirium in patients with and without patient-controlled intravenous analgesia (PCIA) among liver transplant recipients. @*Methods@#The medical records of 253 patients who received liver transplantation (LT) from January 2010 to July 2017 in a single university hospital were retrospectively reviewed. Patients were divided into two groups: the patients who had used PCIA (P group, n = 71) and those who did not use PCIA (C group, n = 182) after LT in intensive care unit (ICU). The patient data were collected, which included demographic data, and details about perioperative management and postoperative complications. @*Results@#There was no difference in the model for end-stage liver disease (MELD) score between the two groups. Postoperative delirium occurred in 10 / 71 (14.08 %) in the P group and 26 / 182 (14.29 %) in the C group after LT, respectively (P = 0.97). After propensity score matching, no differences were observed in the incidence of delirium (P = 0.359) and the time from surgery to discharge (P = 0.26) between the two groups. @*Conclusions@#Patients with PCIA after LT exhibited no relationship with postoperative delirium. Therefore, it is necessary to actively control postoperative pain using PCIA.
ABSTRACT
Background@#Pierre Robin sequence (PRS) patients have an increased risk of difficult intubation due to anatomical airway abnormalities, and intubation simulation with a three-dimensional (3D) printed airway model before anesthesia may facilitate safe airway management. Case: We describe the case of a 6.5-year-old boy with a history of PRS (a triad of micrognathia, glossoptosis, and airway obstruction), tracheostomy, and subglottic fibrosis who required general anesthesia. Preparation for this potentially difficult intubation included estimation of endotracheal tube size using a 3D printed airway model derived from 3D computed tomography of the airway, which enabled successful endotracheal intubation via video laryngoscopy. @*Conclusions@# If general anesthesia is necessary in patients with dysmorphic features such as PRS and there is a history of tracheal pathology, the possibility of difficult intubation should always be considered and simulation of endotracheal intubation using a 3D printed model of the airway can be helpful clinically in such situations.
ABSTRACT
Background@#This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). @*Methods@#We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000– September 2017) at our center. @*Results@#Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34 + cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. @*Conclusion@#Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.
ABSTRACT
This study aimed to investigate whether neurotransmitter receptors in the nervous system were also expressed in oral keratinocytes. Expressions of various neurotransmitter receptor genes in immortalized mouse oral keratinocyte (IMOK) cells were examined by reverse transcriptase polymerase chain reaction. IMOK cells expressed calcitonin gene-related peptide (CGRP) receptor subunit genes Ramp1 and Ramp3 and glutamate receptor subunit genes Grina , Gria3 , Grin1 , Grin2a , and Grin2d . Moreover, IMOK cells expressed Adrb2 and Chrna5 that encode beta 2 adrenergic receptor and cholinergic receptor nicotinic alpha 5 for sympathetic and parasympathetic neurotransmitters, respectively. The expression of Bdkrb1 and Ptger4 , which encode receptors for bradykinin and prostaglandin E2 involved in inflammatory responses, was also observed at low levels. Expressions of Ramp1 and Grina in the mouse gingival epithelium were also confirmed by immunohistochemistry. When the function of neurotransmitter receptors expressed on IMOK cells was tested by intracellular calcium response, CGRP, glutamate, and cholinergic receptors did not respond to their agonists, but the bradykinin receptor responded to bradykinin. Collectively, oral keratinocytes express several neurotransmitter receptors, suggesting the potential regulation of oral epithelial homeostasis by the nervous system.
ABSTRACT
Hemophagocytic syndrome (HPS) is a rare but potentially life-threatening disease in kidney transplant recipients, and is caused by systemic proliferation of macrophages actively phagocytizing other blood cells in the bone marrow, lymph nodes, and the spleen.Here, we report a 40-year-old male kidney transplant recipient who presented with fever, bicytopenia, and elevated liver enzymes 2 months after transplantation. Given that cytomegalovirus antigenemia and real-time polymerase chain reaction tests were positive, liver biopsy was performed under an assumption of cytomegalovirus-induced hepatitis. Hepatic histology revealed multifocal microabscess with cytomegalovirus inclusion bodies, marked Kupffer cell hyperplasia, and erythrophagocytosis by activated macrophages. As laboratory findings such as hyperferritinemia, elevated serum lactate dehydrogenase, low natural killer cell activity, and high soluble interleukin-2 receptor were also compatible with HPS, the recipient was diagnosed as having cytomegalovirus-induced hepatitis combined with reactive HPS. Following intravenous ganciclovir therapy with continuous administration of tacrolimus and corticosteroid, the symptoms resolved and laboratory findings were normalized. As far as we know, this is the first report of cytomegalovirus-induced hepatitis combined with reactive HPS in a kidney transplant recipient that is diagnosed by liver biopsy.
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Background@#Despite significant technological advances in the implantable pulse generator (IPG), complications can still occur. We report a case that unexpected extrusion of the IPG of spinal cord stimulation (SCS) was promptly identified and successfully removed without any complications. Case: After a car accident 4 years ago, a 55-year-old man who was diagnosed with complex local pain syndrome in his right leg. The SCS was inserted with 2 leads, with the IPG being implanted in the right lower abdomen region. Four years later, he developed extrusion of the IPG from his abdominal region. This unexpected extrusion may have been related to pressure necrosis caused by continued compression of pocket site where a belt was frequently tied. The IPG and the leads were successfully removed without infection occurring. @*Conclusions@#To prevent unexpected extrusion of IPG, it is necessary to consider in advance whether the pocket site is pressed against the belt.
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Purpose@#The aim of this study was to investigate celiac plexus neurolysis (CPN) for the treatment of cancerous upper abdominal pain in a tertiary university hospital in Korea. @*Methods@#At the tertiary university hospital in Korea, electronic medical records of cancer patients who underwent CPN and died in the hospital from November 2009 to June 2018 were retrospectively analyzed. @*Results@#The total number of subjects was 51. The 17 patients were from the Department of Gastroenterology (33.0%), followed by 11 patients from the Department of Hemato-oncology (21.6%), 11 patients from the Department of Anesthesia and Pain Medicine (21.6%), 9 patients from the Department of General Surgery (17.6%). The diagnosis was pancreatic cancer in 15 patients (29.4%), stomach cancer in 8 patients (15.7%), hepatobiliary cancer in 20 patients (39.2%), colon cancer in 1 patient (2.0%), esophageal cancer in 2 patient (3.9%) and intra-abdominal metastasis in 5 patients (9.8%). The mean survival time after the surgery was 66.4±55.0 days. The pain intensity before and 1 week after the procedure significantly decreased, but the amounts of opioids consumed before and 1 week after the procedure were not statistically significant. Side effects occurred after the procedure including temporary localized pain in 24 patients (47.0%), hypotension in 12 (23.5%), and diarrhea in 6 (11.8%). @*Conclusion@#CPN is an effective and safe procedure for reducing upper abdominal pain caused by cancer, and it is necessary to perform CPN within the appropriate time by establishing a system of interdepartmental cooperation.
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Background@#There are various reports on the effects of the anesthetic method on neurologic complications. A population-based study was conducted to estimate the effect of anesthetic method on the incidence of postoperative delirium in patients that underwent total hip replacement arthroplasty in South Korea. @*Methods@#The Korean National Health Insurance claims database was used to retrospectively identify and analyze 24,379 cases of total hip replacement arthroplasty, defined as patients having a claim record with the operation code ‘N0711,’ from January 2008 to December 2017. Patients were divided into two groups, a general anesthesia group (n = 9,921) and a regional anesthesia group (n = 14,458). The incidence of delirium was assessed in cases when patients used medications for delirium, such as haloperidol, chlorpromazine, olanzapine, and risperidone. @*Results@#Of the 9,921 patients receiving general anesthesia and 14,458 receiving regional anesthesia, 142 (1.43%) and 209 (0.86%) experienced postoperative delirium after total hip replacement arthroplasty, respectively. There was no significant difference between the groups (P = 0.92). In logistic regression analysis, sex (P = 0.038) and patients with acquired immune deficiency syndrome (P = 0.008) were predictors of postoperative delirium. @*Conclusions@#Our results revealed that the anesthetic method was not associated with the incidence of postoperative delirium. In addition, the results suggest that male patients and patients with acquired immune deficiency syndrome undergoing total hip replacement arthroplasty carefully managed for postoperative delirium after surgery.