Efficacy of Limited Dose Modifications for Palbociclib-Related Grade 3 Neutropenia in Hormone Receptor–Positive Metastatic Breast Cancer / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia. @*Materials and Methods@#Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups. @*Results@#During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality. @*Conclusion@#Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.

Association Between Suggestive Symptom of Restless Legs Syndrome and COVID-19 Vaccination: A Pilot Study

Objectives@#Various sensory symptoms have been recognized after COVID-19 vaccination. Here, we aimed to explore the association between the suggestive symptom of restless legs syndrome (RLSss) and COVID-19 vaccination using an online survey. @*Methods@#We prospectively studied participants who were working in our hospital after at least the first dose of the ChAdOx1 or BNT162b2 mRNA vaccine. The participants were invited via smartphone messages and voluntarily filled out an online questionnaire that included adverse events after vaccination. We considered the participants as having RLSss if they reported that they had three or more symptoms in the restless legs syndrome (RLS) diagnostic criteria. @*Results@#A total of 628 participants (506 female; mean age, 37.7±12.4 years) responded fully to our online survey. 588 participants (93.6%) received the first dose of the ChAdOx1 vaccine (BNT162b2 mRNA vaccine for 40 participants). A total of 44 out of the 628 participants (7.0%) reported that they had RLSss. Myalgia was more common in participants with RLSss than in those without RLSss (97.7% vs. 67.3%, p<0.001). Multivariate testing showed that age (odds ratio, 1.037 per 1 year increase; 95% CI, 1.004–1.071) and the presence of myalgia (odds ratio, 20.479; 95% CI, 4.266–368.206) were associated with the presence of RLSss. @*Conclusions@#This pilot study explored RLSss after COVID-19 vaccination and the results suggested that RLS might be one of the causes of adverse symptoms after COVID-19 vaccination. Further studies are required to confirm the relationship between RLS and COVID-19 vaccination.

Anterior Approach Following Intraoperative Reduction for Cervical Facet Fracture and Dislocation

Objective@#: The purpose of this study was to evaluate the efficacy of the anterior approach following intraoperative reduction under general anesthesia in patients with cervical facet fracture and dislocation. @*Methods@#: Twenty-three patients with single level cervical facet fracture and dislocation who were subjected to the anterior approach alone following immediate intraoperative reduction under general anesthesia from March 2013 to December 2017 were enrolled in this study. Neurological status, clinical outcome, and radiological studies were evaluated preoperatively, postoperatively, and during the follow-up period. @*Results@#: The cohort comprised 15 men and eight women with a mean age of 57 years (from 24 to 81). All patients were operated on within the first 8 hours following the injury. After gentle manual reduction or closed reduction with Gardner-Wells traction, under general anesthesia monitored by somatosensory-evoked potentials, all operations were successfully completed using the anterior approach alone except in two patients, who had a risk of over-distraction. In them, a satisfactory gentle manual reduction or closed reduction was not possible, and required open posterior reduction of the locked facets followed by anterior cervical discectomy and fusion. In one patient, screw retropulsion was observed in 1 month after surgery. There were no reduction-related complications or neurological aggravations after surgery. All patients showed evidence of stability at the instrumented level at the final follow-up (mean follow-up, 12 months). @*Conclusion@#: Anterior approach following intraoperative reduction monitored by somatosensory-evoked potentials under general anesthesia for cervical dislocation and locked facets is a relatively safe and effective alternative when cervical alignment is achieved by intraoperative reduction.

Quercetin-induced apoptosis ameliorates vascular smooth muscle cell senescence through AMP-activated protein kinase signaling pathway

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (H₂O₂) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the anti-apoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.

Tc-99m and Fluorescence-Labeled Anti-Flt1 Peptide as a Multimodal Tumor Imaging Agent Targeting Vascular Endothelial Growth Factor-Receptor 1 / 대한핵의학회잡지

PURPOSE@#We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-GNQWFI, to target tumor cells, and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model.@*METHODS@#TAMRA-GHEG-ECG-GNQWFI was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-GNQWFI with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with U87MG tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy.@*RESULTS@#After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-GNQWFI complexes were prepared in high yield (> 95%). The K(d) of Tc-99m TAMRA-GHEG-ECG-GNQWFI determined by saturation binding was 29.5 ± 4.5 nM. Confocal microscopy images of U87MG cells incubated with TAMRA-GHEG-ECG-GNQWFI showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumors. Tumor uptake was effectively blocked by the co-injection of an excess concentration of GNQWFI. Specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI was assessed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies.@*CONCLUSION@#In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumor cells. Tc-99m TAMRA-GHEG-ECG-GNQWFI could be a good candidate dual-modality imaging agent for tumors.

Malignant Metastasis Misdiagnosed as Osteoporotic Compression Fracture: A Case Report / 대한신경손상학회지

In cases of vertebral collapse after a trivial injury in elderly patients with severe osteoporosis, it can be a diagnostic challenge to determine whether the cause is a benign compression fracture or malignant metastasis. A 78-year-old male patient was referred to the emergency department for the evaluation of weakness of the left lower limb. He had undergone percutaneous vertebroplasty four months earlier after being diagnosed with L3 osteoporotic compression fracture. He was treated with foraminotomy at the L3–4 level after being diagnosed with foraminal stenosis two months earlier at a spine clinic. Magnetic resonance (MR) images showed significant signal change from the vertebral body to the posterior element, and widely spreading extraspinal extension of soft tissue at L3. Computed tomography scan revealed osteolytic changes in regions including the ventral body and pedicle. Emergent decompressive laminectomy and bone biopsy were performed, and the histologic evaluation showed metastatic squamous cell carcinoma. A retrospective review of previous MR images showed obvious pedicle and facet involvement, and paraspinal extension of soft tissue, which are highly suggestive of malignant metastasis.

Tc-99m and Fluorescence-Labeled Anti-Flt1 Peptide as a Multimodal Tumor Imaging Agent Targeting Vascular Endothelial Growth Factor-Receptor 1 / 대한핵의학회잡지

PURPOSE: We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-GNQWFI, to target tumor cells, and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model.METHODS: TAMRA-GHEG-ECG-GNQWFI was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-GNQWFI with Tc-99m was done using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with U87MG tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy.RESULTS: After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-GNQWFI complexes were prepared in high yield (> 95%). The K(d) of Tc-99m TAMRA-GHEG-ECG-GNQWFI determined by saturation binding was 29.5 ± 4.5 nM. Confocal microscopy images of U87MG cells incubated with TAMRA-GHEG-ECG-GNQWFI showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumors. Tumor uptake was effectively blocked by the co-injection of an excess concentration of GNQWFI. Specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI was assessed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies.CONCLUSION: In vivo and in vitro studies revealed substantial and specific uptake of Tc-99m TAMRA-GHEG-ECG-GNQWFI in tumor cells. Tc-99m TAMRA-GHEG-ECG-GNQWFI could be a good candidate dual-modality imaging agent for tumors.

Complications and Socioeconomic Costs Associated With Falls in the Elderly Population

OBJECTIVE: To explore the incidence, characteristics, complications and socioeconomic impacts associated with falls in community-dwelling elderly. METHODS: From September 1, 2015 to October 12, 2015, a questionnaire-based survey was conducted involving a total of 2,012 elderly who lived in Guro-gu (Seoul), Yeongdeungpo-gu (Seoul), Yangpyeong-gu (Gyeonggi-do), Dalseong-gu (Daegu), and Jung-gu (Daegu). The subjects were interviewed using a structured questionnaire to obtain demographic characteristics and comprehensive falling histories. The socioeconomic cost related to falls was estimated using the statistical data provided by the Health Insurance Review and Assessment Service. RESULTS: Falls were recorded in 666 out of the 2,012 subjects (33.1%) during the past year. Frequent falls occurred during December, in the afternoons, when the floor was slippery. The most common injuries included the low back and the most common injury type was sprain. The total direct costs related to falls involving the 2,012 subjects were 303,061,019 KRW (Korean won). The average medical cost related to falls in the 2,012 subjects was 150,627 KRW and the average medical cost of 666 subjects who experienced falls was 455,047 KRW. Estimates of the total population over the age of 60 years showed that the annual direct costs associated with falls in Korea over the age of 60 years were about 1.378 trillion KRW. CONCLUSION: This study was conducted to explore the incidence, characteristics, complications, and socioeconomic impacts of falls in community-dwelling elderly. This study is expected to be used as a source of basic data for the establishment of medical policy for the elderly and the development of a fall prevention program for the elderly in Korea.

Double primary lung adenocarcinoma diagnosed by epidermal growth factor receptor mutation status / 영남의대학술지

A nodular density was detected on a chest radiograph taken from a 57-year-old Korean woman who was visiting a hospital for a routine check. Chest computed tomography revealed a 4.8 cm lobulated mass in the right lung and another focal nodular lesion in the left lung; biopsies of both lungs revealed adenocarcinoma. We conducted DNA sequencing and peptide nucleic acid clamping to investigate the potential double primary lung cancer. The results verified that the mass in the right lung had a mutation in the epidermal growth factor receptor, whereas the nodule in the left lung had a wild-type sequence, showing that these two were genetically different cancers from one another. Thus, we demonstrate that genetic testing is useful in determining double primary lung cancer, and we herein report on this case.

Hemoptysis during general anesthesia in a diabetic patient with healed tuberculosis: a case report / 대한마취과학회지

Hemoptysis is a common complication of pulmonary tuberculosis. Most of the cases of hemoptysis originate from hypertrophied bronchial arteries. Also, diabetes induces pulmonary vascular abnormalities such as endothelial dysfunction, inflammatory infiltration and pulmonary vascular remodeling. A 27-year-old male, with diabetes and a history of tuberculosis, underwent the procedure of pars plana vitrectomy under general anesthesia. After an uneventful intra-operative period, he had hemoptysis prior to extubation. Emergency fiberoptic bronchscopy showed blood plugs and spotted fresh blood at the right upper lobar bronchus. After successful embolization of the bronchial artery, the patient made a recovery and was discharged without experiencing any complication. Predisposing factors of hemoptysis in this case are presumed to be tuberculosis and diabetes. The bleeding might had been caused by the rupture of a weakened artery within the cavity in the right upper lobe, through expansion of the lung during manual ventilation by positive pressure.

Double primary lung adenocarcinoma diagnosed by epidermal growth factor receptor mutation status / 영남의대학술지

A nodular density was detected on a chest radiograph taken from a 57-year-old Korean woman who was visiting a hospital for a routine check. Chest computed tomography revealed a 4.8 cm lobulated mass in the right lung and another focal nodular lesion in the left lung; biopsies of both lungs revealed adenocarcinoma. We conducted DNA sequencing and peptide nucleic acid clamping to investigate the potential double primary lung cancer. The results verified that the mass in the right lung had a mutation in the epidermal growth factor receptor, whereas the nodule in the left lung had a wild-type sequence, showing that these two were genetically different cancers from one another. Thus, we demonstrate that genetic testing is useful in determining double primary lung cancer, and we herein report on this case.

The Younger Patients Have More Better Prognosis in Limited Disease Small Cell Lung Cancer / 결핵및호흡기질환

BACKGROUND: Factors associated with the prognosis of patients with small cell lung cancer (SCLC) is relatively unknown, than of those with non-small cell lung cancer. This study was undertaken to identify the prognostic factors of SCLC. METHODS: The medical records of 333 patients diagnosed with SCLC at tertiary hospital from January 1, 2008, to December 31, 2012 were retrospectively reviewed. Patients were categorized by age (≤65 years vs. >65 years) and by extent of disease (limited disease [LD] vs extensive disease [ED]). Overall survival and progression free survival rates were determined. Factors associated with prognosis were calculated using Cox's proportional hazard regression model. RESULTS: Most baseline characteristics were similar in the LD and ED groups. Eastern Cooperative Oncology Group (ECOG) performance status (PS), first chemotherapy regimen, and prophylactic cranial irradiation (PCI) differed significantly in patients with LD and ED. Mean ECOG PS was significantly lower (p65 years) patients, but prognosis in the ED group was unrelated to age. CONCLUSION: This study showed that overall survival (OS) was significantly improved in younger than in older patients with LD-SCLC. Univariate and multivariate analyses showed that age, PCI and the sum of cycles were significant predictors of OS in patients with LD-SCLC. However, prognosis in the ED group was unrelated to age.