• Tuberculosis and Respiratory Diseases
• /
• v.85 no.2
• /
• pp.155-164
• /
• 2022

Background: The remarkable efficacy of osimertinib in non-small cell lung cancer (NSCLC) with acquired T790M mutation has been widely documented in clinical trials and real-world practice. However, some patients show primary resistance to this drug. Even patients who initially show a favorable response have inconsistent clinical outcomes later. Therefore, the aim of this study was to identify additional clinical predictive factors for osimertinib efficacy. Methods: A prospective cohort of patients with acquired T790M positive stage IV lung adenocarcinoma treated with osimertinib salvage therapy in Hallym University Medical Center were analyzed. Results: Sixty-one eligible patients were analyzed, including 38 (62%) women and 39 (64%) who never smoked. Their mean age was 63.3 years. The median follow-up after treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) was 36.0 months (interquartile range, 24.7-50.2 months). The majority (n=45, 74%) of patients were deceased. Based on univariate analysis, low baseline neutrophil-to-lymphocyte ratios (NLR), age ≥50 years, never-smoking history, stage IVA at osimertinib initiation, and prolonged response to previous TKIs (≥10 months) were associated with a significantly longer progression-free survival (PFS). Multivariate analysis showed that never-smoking status (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.30-0.98; p=0.041) and a baseline NLR less than or equal to 3.5 (HR, 0.23; 95% CI, 0.12-0.45; p<0.001) were independently associated with a prolonged PFS with osimertinib. Conclusion: Smoking history and high NLR were independent negative predictors of osimertinib PFS in patients with advanced NSCLC developing EGFR T790M resistance after the initial EGFR-TKI treatment.

• Korean Journal of Biological Psychiatry
• /
• v.12 no.2
• /
• pp.98-106
• /
• 2005

Objectives:Donepezil is a widely used drug for the treatment of patients with Alzheimer's disease(AD). The aim of the present study was to clarify the efficacy and the characteristics of responders to donepezil. Methods:Patients with probable AD(n=80;75.7 years) and small vessel dementia(SVD)(n=18;77.8 years) who received donepezil were retrospectively analyzed using Alzheimer's registry, and three questions were asked:1) Does donepezil therapy improves cognitive symptoms in patients with dementia? 2) If donepezil improves cognitive symptoms, which items of the K-MMSE are improved? 3) What are the characteristics of responder to donepezil medication? Results:1) After donepezil medication, cognitive function measured by the K-MMSE was significantly improved in both types of dementia(AD and SVD), However, statistical differences were not found between these groups. 2) In a clinical trial of donepezil, the patients performed better than before mediation on K-MMSE items assessing orientation, recall, construction, concentration, calculation. 3) In AD, the K-MMSE score before medication was closely related with response of donepezil. Conclusion:This study suggests that donepezil improves various cognitive functions in both types of dementia, and the responsive group had significantly lower K-MMSE scores than the non-responsive group before medication.

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.1
• /
• pp.61-66
• /
• 2014

Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigallocatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.

• Journal of Korean Neurosurgical Society
• /
• v.61 no.5
• /
• pp.640-644
• /
• 2018

Objective : The purpose of this pilot study was to examine the safety and function of the newly developed cerebrospinal fluid (CSF) reservoir called the V-Port. Methods : The newly developed V-Port consists of a non-collapsible reservoir outlined with a titanium cage and a connector for the ventricular catheter to be assembled. It is designed to be better palpated and more durable to multiple punctures than the Ommaya reservoir. A total of nine patients diagnosed with leptomeningeal carcinomatosis were selected for V-Port insertion. Each patient was followed up for evaluation for a month after the operation. Results : The average operation time for V-Port insertion was 42 minutes and the average incision size was 6.6 cm. The surgical technique of V-Port insertion was found to be intuitive by all neurosurgeons who participated in the pilot study. There was no obstruction or leakage of the V-Port during intrathecal chemotherapy or CSF drainage. Also, there were no complications including post-operative intracerebral hemorrhage, infection and skin problems related to the V-Port. Conclusion : V-Port is a safe and an easy to use implantable CSF reservoir that addresses problems of other implantable CSF reservoirs. Further multicenter clinical trial is needed to prove the safety and the function of the V-Port.

• The Journal of Internal Korean Medicine
• /
• v.40 no.6
• /
• pp.1081-1100
• /
• 2019

Objectives: This study is an overview of the meta-analysis and systematic review of randomized controlled trials investigating the clinical effectiveness and safety of pharmacopuncture for patients with stroke. Methods: Core electronic databases were searched from their inception to 21 May 2019. A measurement tool to assess systematic reviews (AMSTAR 2) was applied to screen high-quality studies. The results of these studies were summarized, and additional meta-analysis was conducted. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the certainty of evidence. Results: Sixteen studies met eligibility criteria. Four were excluded owing to insufficiency of AMSTAR 2 or low data reliability. The finally selected 12 studies were about pharmacopuncture using either a single herb extract, such as Dengzhan xixin, Sanch, Ginkgo biloba, or Acanthopanax, or a mixture of herbs, such as Compound danshen, Shenxiong, Xingnaojing, or Mailuoning. Most of the patients were from China, with acute ischemic stroke. All the studies using a pharmacopuncture versus a non-pharmacopuncture design reported the significant superiority of pharmacopuncture on every outcome measure. On the other hand, in a few studies, pharmacopuncture was inferior to active control in improving neurological deficit. Few studies reported adverse events. Conclusions: It is difficult to apply the results of this study directly to Korea, because the level of evidence is generally low and the clinical settings and social acceptance of pharmacopuncture therapy differ in Korea and China. Further studies are warranted to confirm the domestic applicability of evidence generated in China and to create evidence that supports the domestic situation.

• Korean Journal of Clinical Pharmacy
• /
• v.28 no.1
• /
• pp.17-23
• /
• 2018

Objective: Opioid analgesics, for postoperative pain management, are an indispensable group of medication; however, they also have a variety of adverse drug reactions (ADR). Multimodal methods, combining non-opioid analgesics with opioid analgesics, have been investigated to increase the effects of analgesics and reduce ADR with opioid-sparing effects. The purpose of this study was to compare the effects of patient-controlled analgesia (PCA) with fentanyl alone, and PCA with fentanyl and intravenous (i.v.) propacetamol to determine the effects of pain control, cumulative opioid usage, and opioid ADR. Methods: The subjects were patients who underwent total knee arthroplasty at the Seoul Veterans hospital from January 1, 2015 to December 31, 2016. The study period was from postoperative day 0 (POD0) to day 3 (POD3), and the retrospective study was conducted using electronic medical records. Results: Pain severity was significantly low at POD1 (p = 0.017), POD2 (p = 0.003), and POD3 (p = 0.002) in the multimodal group. The fentanyl only group frequently reported both moderate and severe pain at a statistically significant level. This was consistent with the analysis of the pro re nata (PRN) intramuscular analgesia usage at the time of numerical rating scale (NRS) 4 and above. The opioid-sparing effect confirmed that the average opioid dose equivalent to i.v. morphine dose was 9.4 mg more than that used for the multimodal group in the fentanyl only group. The ADRs and length of stay between the two groups were not statistically different. Conclusion: The results of this study suggest that the combination therapy of fentanyl and i.v. propacetamol is superior to fentanyl monotherapy.

• Journal of Yeungnam Medical Science
• /
• v.11 no.1
• /
• pp.186-192
• /
• 1994

Amiodarone has a potent suppressive effect on supraventricular and ventricular dysrhythmias, so has widely used as a class III antiarrhythmic agent. However, significant side effects were noted in over 50% of patients treated. Pulmonary toxicity represents the most serious adverse raeaction limiting the clinical efficacy of this new antidysrhythmic drug. A 66-year-old male had received amiodarone 200mg/day for 7 months to control high grade ventricular premature contraction and was admitted due to dyspnea on exertion for 1 week. At the time of admission end-inspiratory crepitant rale was heard on auscultation. The roentgenogram of his chest revealed reticular and granular radioopaque densities on both lower lung fields and high resonance CT revealed interstitial fibrosis and pneumonic consolidations on the periphery of the both middle and lower lobes. Trans-bronchoscopic lung biopsy revealed nonspecific intersitial fibrosis. The laboratory findings were non-specific. We present a case of amiodarone-induced interstitial pulmonary disease clinically improved by cortico-steroid therapy.

• Clinical and Experimental Pediatrics
• /
• v.50 no.10
• /
• pp.931-937
• /
• 2007

The hemolytic uremic syndrome (HUS) is a rare disease of microangiopathic hemolytic anemia, low platelet count and renal impairment. HUS usually occurs in young children after hemorrhagic colitis by shigatoxin-producing enterohemorrhagic E. coli (D+HUS). HUS is the most common cause of acute renal failure in infants and young children, and is a substantial cause of acute mortality and morbidity; however, renal function recovers in most of them. About 10% of children with HUS do not reveal preceding diarrheal illness, and is referred to as D- HUS or atypical HUS. Atypical HUS comprises a heterogeneous group of thrombomicroangiopathy (TMA) triggered by non-enteric infection, virus, drug, malignancies, transplantation, and other underlying medical condition. Emerging data indicate dysregulation of alternative complement pathway in atypical HUS, and genetic analyses have identified mutations of several regulatory genes; i.e. the fluid phase complement regulator Factor H (CFH), the integral membrane regulator membrane cofactor protein (MCP; CD46) and the serine protease Factor I (IF). The uncontrolled activation of the complement alternative pathway results in the excessive consumption of C3. Plasma exchange or plasma infusion is recommended for treatment of, and has dropped the mortality rate. However, overall prognosis is poor, and many patients succumb to end-stage renal disease. Clinical presentations, response to plasma therapy, and outcome after renal transplantation are influenced by the genotype of the complement regulators. Thrombotic thrombocytopenic purpura (TTP), another type of TMA, occurs mainly in adults as an acquired disease accompanied by fever, neurologic deficits and renal abnormalities. However, less frequent cases of congenital or hereditary TTP associated with ADAMTS-13 (a disintegrin and metalloprotease, with thrombospondin 1-like domains 13) gene mutations have been reported, also. Recent advances in molecular genetics better allow various HUS to be distinguished on the basis of their pathogenesis. The genetic analysis of HUS is important in defining the underlying etiology, predicting the genotype-related outcome and optimizing the management of the patients.

• Tuberculosis and Respiratory Diseases
• /
• v.55 no.6
• /
• pp.631-635
• /
• 2003

Idiopathic interstitial pneumonia is a group of lung disease classified by clinical, radiological and pathologic findings. Steroid is described in many reports as an effective treatment for the idiopathic interstitial pneumonitis. For the treatment of steroid non-responders, immuno-suppressive or cytotoxic agents are used as second line drug of choice. We experienced a case of nonspecific interstitial pneumonitis who was treated initially with glucocorticoid and antibiotics without effects, but later did respond to cyclosporin treatment. This 63 year-old patient was admitted due to dyspnea, cough, and sputum production. He was started on glucocorticoid and antibiotics after he was diagnosed as having nonspecific interstitial pneumonitis by open lung biopsy. The initial steroid treatment was not effective, however, after cyclosprin treatment, the patient showed clinical and radiologic improvements.

• Tuberculosis and Respiratory Diseases
• /
• v.76 no.2
• /
• pp.66-74
• /
• 2014

Background: The increasing number of outpatients with multidrug-resistant (MDR) pathogens has led to a new category of pneumonia, termed healthcare-associated pneumonia (HCAP). We determined the differences in etiology and outcomes between patients with HCAP and those with community-acquired pneumonia (CAP) to clarify the risk factors for HCAP mortality. Methods: A retrospective study comparing patients with HCAP and CAP at Jeju National University Hospital. The primary outcome was 30-day mortality. Results: A total of 483 patients (208 patients HCAP, 275 patients with CAP) were evaluated. Patients with HCAP were older than those with CAP (median, 74 years; interquartile range [IQR], 65-81 vs. median, 69 years; IQR, 52-78; p<0.0001). Streptococcus pneumoniae was the major pathogen in both groups, and MDR pathogens were isolated more frequently from patients with HCAP than with CAP (18.8% vs. 4.9%, p<0.0001). Initial pneumonia severity was greater in patients with HCAP than with CAP. The total 30-day mortality rate was 9.9% and was higher in patients with HCAP based on univariate analysis (16.3% vs. 5.1%; odds ratio (OR), 3.64; 95% confidence interval (CI), 1.90-6.99; p<0.0001). After adjusting for age, sex, comorbidities, and initial severity, the association between HCAP and 30-day mortality became non-significant (OR, 1.98; 95% CI, 0.94-4.18; p=0.167). Conclusion: HCAP was a common cause of hospital admissions and was associated with a high mortality rate. This increased mortality was related primarily to age and initial clinical vital signs, rather than combination antibiotic therapy or type of pneumonia.