Efficacy of lazertinib for symptomatic or asymptomatic brain metastases in treatment-naive patients with advanced EGFR mutation-positive non-small cell lung cancer: Protocol of an open-label, single-arm phase II trial.

INTRODUCTION: Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation has a higher incidence of brain metastases than wild-type EGFR mutations. Osimertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), targets both EGFR-TKI sensitizing and T790M-resistance mutations and has a higher brain penetration rate relative to first- and second-generation EGFR-TKIs. Therefore, osimertinib has become a preferred first-line therapy for advanced EGFR mutation-positive NSCLC. However, lazertinib, an emerging EGFR-TKI, has shown higher selectivity toward EGFR mutations and improved penetration of the blood-brain barrier compared to osimertinib in preclinical studies. This trial will evaluate the efficacy of lazertinib as a first-line therapy in patients with EGFR mutation-positive NSCLC who have brain metastases, with or without additional local therapy. METHODS: This is a single-center, open-label, single-arm phase II trial. A total of 75 patients with advanced EGFR mutation-positive NSCLC will be recruited. Eligible patients will receive oral lazertinib 240 mg, once daily until disease progression or intolerable toxicity is detected. Patients with moderate to severe symptoms related to brain metastasis will simultaneously receive local therapy for the brain. The primary endpoints are progression-free survival and intracranial progression-free survival. DISCUSSION: Lazertinib, in combination with local therapy for the brain, if necessary, is expected to improve the clinical benefit in advanced EGFR mutation-positive NSCLC with brain metastases, as a first-line treatment.

Effect of Growth Stages on Anthocyanins and Polyphenols in the Root System of Sweet Potato.

The storage roots of purple-fleshed sweet potato contain a variety of anthocyanins and polyphenols. Little is known about changes in the total content and composition of anthocyanins and polyphenols in the early growth stages of the root system. In this study, we investigated the changes in anthocyanins and polyphenols in the root system of purple-fleshed sweet potato cultivars at 15, 30, 45, and 60 days after transplant (DAT). Unexpectedly, the highest percentage of acylated anthocyanins in three purple-fleshed cultivars among all growth stages was at 15 DAT. On the other hand, the total polyphenol content in the early growth stages of the root system increased rapidly toward 45 DAT, just before the beginning of storage root enlargement, and then decreased rapidly as the storage roots began to enlarge. These data indicate that the early growth stage of the root system is a critical time. This timing may present a strategy to maximize the accumulation of polyphenols with high antioxidant activity, as well as acylated anthocyanins, to protect against abiotic and biotic stresses.

Effect of remifentanil during drug-induced sleep endoscopy in patients with obstructive sleep apnea.

PURPOSE: During drug-induced sleep endoscopy (DISE) in patients with obstructive sleep apnea, the increased depth of propofol anesthesia is related to the increased collapsibility of the upper airway with dose-dependent. We examined the effect of remifentanil on propofol concentration during DISE. METHODS: In a prospective randomized trial, 56 adult patients were divided into remifentanil-propofol (n = 28) and propofol alone (n = 28) groups. Anesthesia was administered using a target-controlled infusion system. In the remifentanil-propofol group, 0.5 ng/ml remifentanil was administered prior to propofol infusion and its concentration maintained; thereafter, in the propofol alone group, normal saline was injected instead of remifentanil. Propofol was infused at a concentration of 1.5 µg/ml after the target concentration of remifentanil was reached. In both groups, the concentration of propofol was increased by 0.5 µg/ml if the degree of sedation was not sufficient. The sedation level was targeted at observer's assessment of alertness/sedation (OAA/S) scale 3. RESULTS: The mean propofol concentration was 2.87 ± 0.60 µg/ml in the remifentanil-propofol group, which was lower than that in the propofol alone group (3.38 ± 0.72 µg/ml, P < 0.001). The time until sufficient sedation to perform DISE was shorter in the remifentanil-propofol group (P < 0.001). Apnea-hypopnea index and the lowest peripheral capillary oxygen saturation (SpO2) during polysomnography showed no statistical difference between groups (P > 0.05). The lowest SpO2 and VOTE classification during DISE were also not statistically different (P > 0.05). CONCLUSIONS: Use of remifentanil during DISE reduces the target concentration of propofol required for patient sedation to perform DISE without respiratory depression.

Palonosetron-Induced Anaphylaxis During General Anesthesia: A Case Report.

Palonosetron is a 5-hydroxytryptamine-3 (5-HT-3) receptor antagonist used for preventing postoperative nausea and vomiting. Compared with ondansetron and granisetron, it is a better drug because of prolonged action and minimal side effects. Some adverse effects of palonosetron have been reported. In this report, we describe a 37-year-old male who developed severe hypersensitivity reactions to palonosetron during surgery for kidney donation. His medical history was unremarkable, except for inguinal hernia with herniorrhaphy 8 years ago. The surgery was uneventful until 2 hours 20 minutes. After palonosetron injection, his blood pressure dropped to 80/50 mm Hg, and facial edema, rash, conjunctival swelling, and wheezing developed. The patient was resuscitated by administration of ephedrine, hydrocortisone, and peniramine. Following the surgery, the patient was monitored for 3 days, and there were no subsequent anaphylactic reactions or other complications. The skin test on postoperative day 54 was positive for hypersensitivity to palonosetron. Although palonosetron is known for its safety, other hypersensitivity events have been reported. Ondansetron is another widely used 5-HT-3 antagonist, which has been reported to cause anaphylaxis. Therefore, clinicians should be aware of the possibility of patients experiencing severe adverse reactions to palonosetron.

Ability of an intentionally smaller anterior than posterior gap to reduce the sagittal tibial slope in opening wedge high tibial osteotomy.

BACKGROUND: We utilized in vivo 3- dimensional (D) computed tomography (CT) to determine whether the preoperatively planned anterior and posterior opening gap heights correlated with the real gaps following opening wedge high tibial osteotomy (HTO), as well as the relationships between anterior and posterior gap heights and change in sagittal tibial slope. METHODS: This prospective study involved 41 patients (41 knees) undergoing navigation HTO for primary medial osteoarthritis. Mechanical axis (MA), weight-bearing line (WBL) ratio, and posterior tibial slope were measured on radiographs preoperatively and after 3 months. The anterior and posterior opening gaps created by osteotomy were measured using in vivo 3D CT and the patients were classified into a larger anterior or posterior gap group. RESULTS: Of the 41 patients, 24 (59 %) had larger anterior and 17 (41 %) had larger posterior gaps. There were no between group differences in preoperative and postoperative slopes, or in change in slope. The correlation between preoperatively planned and postoperative posterior gaps was good, whereas the correlation of anterior gaps was only fair. Bland-Altman plots showed poor agreement for both preoperative and postoperative anterior and posterior gaps. The mean systematic difference (bias) was 2.3 mm (p < 0.001) for anterior and -1.0 mm (p = 0.033) for posterior gaps. CONCLUSIONS: Preoperatively calculated opening gaps, which were planned to be larger posteriorly than anteriorly to minimize the change in slope after surgery, did not correspond with postoperative opening gaps on 3D CT. In addition, postoperative tibial slope did not increase, even when the anterior gap was larger than the posterior gap. TRIAL REGISTRATION NUMBER: KCT0001905 , April 29, 2016.

Clinical characteristics and molecular genetic analysis of Korean patients with GNE myopathy.

PURPOSE: Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase (GNE) myopathy is an autosomal recessive neuromuscular disorder characterized by early adult-onset weakness of the distal muscles of the lower limbs. The clinical spectrum of GNE myopathy varies, and it is not clear how the same GNE gene mutations can result in different phenotypes. Here, we present clinical, pathological and genetic characteristics of twenty-one Korean patients with GNE myopathy. MATERIALS AND METHODS: Twenty-one GNE myopathy patients were included in this study, conducted from 2004 to 2011. Based on medical records, patients' gender, onset age, family history, clinical history, serum creatine kinase (CK) level, neurologic examination, findings of muscle biopsy, muscle imaging findings and electrophysiologic features were extensively reviewed. Mutation of the GNE gene (9p13.3) was confirmed by DNA direct sequencing analysis in all patients. RESULTS: The mean onset age was 23.8±8.8 years (mean±SD). Patient serum CK levels were slightly to moderately elevated, ranging from 41 to 2610 IU. Among the patients, twelve patients were female and nine patients were male. Except for eight patients, all of the patients presented initially with only distal muscle weakness in the lower extremities. The most common mutation was V572L, followed by C13S. CONCLUSION: The clinical manifestations of our patients with GNE mutations varied. Among twenty-one patients, thirteen patients showed the typical GNE myopathy phenotype. There was no relationship between clinical features and site of mutation. Therefore, we suggest that neither homozygous nor compound heterozygous models are correlated with disease phenotype or disease severity.