Comorbidities and the use of comedications among patients with chronic hepatitis C in Korea: A nationwide cross-sectional study

Background/Aims@#Chronic hepatitis C (CHC) is the second leading cause of liver-related mortality and is more prevalent in the elderly population in Korea. Decisions to initiate treatment and selection of proper antiviral agents may be challenging among elderly patients due to relevant comorbidities, comedications, and drug-drug interaction (DDI). It may be helpful to understand the current demographic status and comorbidities of CHC patients in the country. @*Methods@#Patients aged ≥ 18 years and diagnosed with CHC (KCD-7 code B18.2) were extracted from the Korean Health Insurance Review & Assessment Service database in 2018. Data on comorbidities and comedications were assessed and potential DDIs were analyzed. @*Results@#A total of 50,476 patients with CHC, with a mean age of 60.3 years and 46.7% male patients were identified. The proportion of patients with cirrhosis, hepatocellular carcinoma, and liver transplantation was 6.0%, 4.1%, and 0.3%, respectively and 37.2% of patients were more than 65 years of age. The three most common comorbidities were diseases of the digestive system (83.7%), respiratory system (58.2%), and musculoskeletal system and connective tissue (57.6%). The three most common comedications were analgesics (91.6%), gastrointestinal agents (85%), and antibacterials (80.3%). Lipid-lowering agents and anticonvulsants were prescribed in 28.5% and 14.8% of patients. Rate of potential DDI for contraindication was 2.2%, 13.1%, and 15.6% with sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, and glecaprevir/pibrentasvir. @*Conclusions@#With the increasing age of patients with CHC, comorbidity, comedication, and potential DDI should be considered when choosing antivirals in Korea. Sofosbuvir-based regimens showed favorable DDI profiles among Korean patients.

Association between eupatilin and reduction in small bowel bleeding in aspirin users and aspirin plus acid suppressant users

Background/Aims@#Capsule endoscopy (CE) has shown that low-dose aspirin occasionally causes small bowel (SB) bleeding. We herein evaluated the protective effects of mucoprotective agents (MPAs) on SB bleeding in aspirin users using the nationwide database of claims data from the National Health Insurance Service (NHIS). @*Methods@#As CE is an insured procedure, we constructed an aspirin-SB cohort using NHIS claims data, with a maximum follow- up period of 24 months. Patients with anemia, melena, or hematochezia that occurred within 4 weeks before and after performing CE were suspected to have SB bleeding. A Cox proportional hazards regression model was used to determine the risk factors for SB bleeding. Subgroup analyses were conducted among patients who used acid suppressants, such as proton pump inhibitors (PPIs) and histamine-2 receptor antagonists. @*Results@#A total of 15,542 aspirin users were included. Anticoagulant use (hazard ratio [HR], 3.22), high Charlson comorbidity index score (≥ 2) (HR, 3.54), and PPI use (HR, 2.85) were significantly associated with SB bleeding, whereas eupatilin use (HR, 0.35) was a preventive factor. SB bleeding occurred more frequently in concurrent users of acid suppressants than in nonusers (1.3% vs. 0.5%). Subgroup analysis revealed that eupatilin significantly reduced the risk of SB bleeding in aspirin users with concurrent use of acid suppressants (HR, 0.23 vs. 2.55). @*Conclusions@#Eupatilin was associated with a reduced risk of SB bleeding in both aspirin users and those with concomitant use of acid suppressants. Eupatilin use should be considered for aspirin users, especially for those concomitantly taking acid suppressants.

Hypofractionated Radiotherapy for Early-Stage Breast Cancer: A Propensity Score Matched Analysis

Background@#In patients with early-stage breast cancer, the treatment results of hypofractionated radiation therapy (RT) and conventional RT are evaluated in efficacy and cost. @*Methods@#We retrospectively evaluated 280 patients with early-stage (Tis-2N0M0) breast cancer (including 100 hypofractionated RT patients) with regards to treatment outcomes according to the RT schedule. The median whole-breast RT dose was 42.56 Gy/16 fractions for hypofractionated RT and 50.4 Gy/28 fractions for conventional RT. Most patients (n = 260, 92.9%) additionally received a tumor bed boost RT. We used propensity score matching (PSM) analysis to balance the baseline risk factors for recurrence. The co-primary endpoints of this study were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR).DFS or IBTR was analyzed using the Kaplan-Meier survival curve and log-rank test. @*Results@#Total 89 pairs of matched patients (1:1 matching, n = 178) were finally evaluated.The median follow-up was 23.6 months. After matching, the 3-year DFS was 100% in the hypofractionated RT group and 98.4% in the conventional RT group; there was no significant difference in DFS between the groups (P = 0.374). Furthermore, the IBTR did not differ between the hypofractionated RT and conventional RT groups (P = 0.374) after matching. The 3-year overall survival was not different between two groups (both 100%). Hypofractionated RT saved 26.6% of the total cost of RT compared to conventional RT. Additionally, the acute skin toxicity rate (≥ grade 2) was also not significantly different between the groups (hypofractionated RT: 10.1% vs. conventional RT: 2.2%). @*Conclusion@#Hypofractionated RT showed good IBTR and DFS, which were compatible to those in conventional RT in breast cancer. Hypofractionated RT is expected to be used more widely because of its low cost and convenience.

Alpha-Synuclein Inclusion Formation in Human Oligodendrocytes

Multiple system atrophy (MSA) is a neurodegenerative disease characterized by presence of α-synuclein-positive inclusions in the cytoplasm of oligodendrocytes. These glial cytoplasmic inclusions (GCIs) are considered an integral part of the pathogenesis of MSA, leading to demyelination and neuronal demise. What is most puzzling in the research fields of GCIs is the origin of α-synuclein aggregates in GCIs, since adult oligodendrocytes do not express high levels of α-synuclein. The most recent leading hypothesis is that GCIs form via transfer and accumulation of α-synuclein from neurons to oligodendrocytes. However, studies regarding this subject are limited due to the absence of proper human cell models, to demonstrate the entry and accumulation of neuronal α-synuclein in human oligodendrocytes. Here, we generated mature human oligodendrocytes that can take up neuronderived α-synuclein and form GCI-like inclusions. Mature human oligodendrocytes are derived from neural stem cells via “oligosphere” formation and then into oligodendrocytes, treating the cells with the proper differentiation factors at each step. In the final cell preparations, oligodendrocytes consist of the majority population, while some astrocytes and unidentified stem cell-like cells were present as well. When these cells were exposed to α-synuclein proteins secreted from neuron-like human neuroblastoma cells, oligodendrocytes developed perinuclear inclusion bodies with α-synuclein immunoreactivity, resembling GCIs, while the stem cell-like cells showed α-synuclein-positive, scattered puncta in the cytoplasm. In conclusion, we have established a human oligodendrocyte model for the study of GCI formation, and the characterization and use of this model might pave the way for understanding the pathogenesis of MSA.

Nutrition Management in Diabetes Patients during COVID-19: The Role of Nutrients in Immunity / 임상당뇨병

Diabetes patients are vulnerable to coronavirus disease 2019 (COVID-19) infection. Therefore, challenges arise concerning how to manage nutrition support to strengthen the immune system in diabetes patients. The purpose of this paper is to review the roles of macronutrients and specific micronutrients such as vitamin D, B12, folate, selenium, and zinc in supporting the immune system and examine the nutritional management method of diabetes patients during the COVID-19 pandemic. Evidence indicates that adequate amounts of protein, high omega-3 fatty acids, low refined sugars, high fiber content such as whole grains, and micronutrients including vitamin D, Bsub>12, folate, selenium, and zinc impact immune system function in diabetes patients. Consumption of a balanced diet with these nutrients is best to support the immune system in diabetes patients during the COVID-19 pandemic.

Oxaliplatin-induced Peripheral Neuropathy, Symptoms, Distress and Quality of Life among Korean Patients with Gastrointestinal Cancer

PURPOSE: This study was conducted to identify the level of oxaliplatin-induced peripheral neuropathy (OIPN), symptoms, distress, and quality of life (QoL) in gastrointestinal (GI) cancer patients and to identify the factors influencing QoL.METHODS: A total of 123 patients were recruited for this cross-sectional study. Surveys used were the Therapy-Induced Neuropathy Assessment Scale (TNAS) for OIPN, the MD Anderson Symptom Inventory (MDASI-GI) for general symptoms associated with gastrointestinal cancer and its treatment, a distress thermometer, and the Euro Quality of Life Questionnaire 5-Dimensional Classification (EQ-5D) for QoL.RESULTS: The patients were classified into three groups based on their treatment completion time (current, completed less than one year ago, completed more than one year ago). The scores of MDASI-GI and distress were significantly lower in patients who had completed chemotherapy compared to those who were undergoing treatment (p=.04 and .02 respectively). However, TNAS score was significantly higher in patients who completed chemotherapy less than one year ago than the other two groups (p=.001). In multivariate regression models, the OIPN and distress or general symptoms were identified as factors associated with QoL.CONCLUSION: In this study, we identified the symptoms that are factors related to the QoL in patients with GI cancer. In particular, the symptoms of OIPN are reported at significantly increased levels for patients who have finished chemotherapy less than one year ago, so efforts to prevent and manage the symptoms of OIPN are needed in this timeframe. To improve QoL of patients with GI cancer, continuous attention and care are required not only during the treatment of cancer but also after the completion of treatment.

Ki-67 labeling index as a prognostic marker in advanced stomach cancer

PURPOSE: Proliferation marker Ki-67 is widely used in cancer prognosis prediction. We tried to investigate the role of Ki-67 as a prognostic factor in stomach cancer after surgery in this study. METHODS: We retrospectively evaluated 251 patients who underwent curative resection for gastric cancer from 2010 to 2015. In pathologic examination, Ki-67 labeling index was defined as the percentage of Ki-67 antigen positive cells. Prognostic significance of Ki-67 for gastric cancer was evaluated. Disease-free survival (DFS) was assessed as a primary end-point. RESULTS: The median follow-up period was 28.0 months. Thirty-one patients (12.4%) showed Ki-67 labeling index (LI) lower than 25%. Sixty-eight patients (26.6%) showed recurrence during follow-up period. Recurrence was associated with Ki-67 LI level (≤25%, P = 0.016), and lymph node metastasis status (P = 0.002). High Ki-67 LI level (>25%) was also related to p53 positivity (P < 0.001) and poorly cohesive type (P = 0.002). The 3-year DFS was 69.4%. Low Ki-67 LI level (≤25%) was related with low DFS (47.6% vs. 72.6%, P = 0.016). T stage (P < 0.001), N stage (P = 0.006), lymphovascular invasion (P = 0.010), and neuronal invasion (P = 0.001) also affected the DFS. In addition, T stage (P = 0.03) and Ki-67 LI (P = 0.035) were independent prognostic factors for DFS. In patients treated with adjuvant chemotherapy (n = 239, 93.4%), low Ki-67 (≤25%) was a poor prognostic factor for DFS (P = 0.013). CONCLUSION: Low Ki-67 LI predicts high rate of progression and low DFS of stomach cancer. Ki-67 LI can be a predictive marker in resected stomach cancer treated with surgery and adjuvant chemotherapy.

7,8-Dihydroxyflavone Protects High Glucose-Damaged Neuronal Cells against Oxidative Stress

Oxidative stress is considered a major contributor in the pathogenesis of diabetic neuropathy and in diabetes complications, such as nephropathy and cardiovascular diseases. Diabetic neuropathy, which is the most frequent complications of diabetes, affect sensory, motor, and autonomic nerves. This study aimed to investigate whether 7,8-dihydroxyflavone (7,8-DHF) protects SH-SY5Y neuronal cells against high glucose-induced toxicity. In the current study, we found that diabetic patients exhibited higher lipid peroxidation caused by oxidative stress than healthy subjects. 7,8-DHF exhibits superoxide anion and hydroxyl radical scavenging activities. High glucose-induced toxicity severely damaged SH-SY5Y neuronal cells, causing mitochondrial depolarization; however, 7,8-DHF recovered mitochondrial polarization. Furthermore, 7,8-DHF effectively modulated the expression of pro-apoptotic protein (Bax) and anti-apoptotic protein (Bcl-2) under high glucose, thus inhibiting the activation of caspase signaling pathways. These results indicate that 7,8-DHF has antioxidant effects and protects cells from apoptotic cell death induced by high glucose. Thus, 7,8-DHF may be developed into a promising candidate for the treatment of diabetic neuropathy.

Purpurogallin Protects Keratinocytes from Damage and Apoptosis Induced by Ultraviolet B Radiation and Particulate Matter 2.5

Purpurogallin, a natural phenol obtained from oak nutgalls, has been shown to possess antioxidant, anticancer, and anti-inflammatory effects. Recently, in addition to ultraviolet B (UVB) radiation that induces cell apoptosis via oxidative stress, particulate matter 2.5 (PM(2.5)) was shown to trigger excessive production of reactive oxygen species. In this study, we observed that UVB radiation and PM(2.5) severely damaged human HaCaT keratinocytes, disrupting cellular DNA, lipids, and proteins and causing mitochondrial depolarization. Purpurogallin protected HaCaT cells from apoptosis induced by UVB radiation and/or PM(2.5). Furthermore, purpurogallin effectively modulates the pro-apoptotic and anti-apoptotic proteins under UVB irradiation via caspase signaling pathways. Additionally, purpurogallin reduced apoptosis via MAPK signaling pathways, as demonstrated using MAPK-p38, ERK, and JNK inhibitors. These results indicate that purpurogallin possesses antioxidant effects and protects cells from damage and apoptosis induced by UVB radiation and PM(2.5).

Maximum standardized uptake value at pre-treatment PET in estimating lung cancer progression after stereotactic body radiotherapy

PURPOSE: This study aimed to identify the feasibility of the maximum standardized uptake value (SUVmax) on baseline 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) as a predictive factor for prognosis in early stage primary lung cancer treated with stereotactic body radiotherapy (SBRT). MATERIALS AND METHODS: Twenty-seven T1-3N0M0 primary lung cancer patients treated with curative SBRT between 2010 and 2018 were retrospectively evaluated. Four patients (14.8%) treated with SBRT to address residual tumor after wedge resection and one patient (3.7%) with local recurrence after resection were included. The SUVmax at baseline PET/CT was assessed to determine its relationship with prognosis after SBRT. Patients were divided into two groups based on maximum SUVmax on pre-treatment FDG PET/CT, estimated by receiver operating characteristic curve. RESULTS: The median follow-up period was 17.7 months (range, 2.3 to 60.0 months). The actuarial 2-year local control, progressionfree survival (PFS), and overall survival were 80.4%, 66.0%, and 78.2%, respectively. With regard to failure patterns, 5 patients exhibited local failure (in-field failure, 18.5%), 1 (3.7%) experienced regional nodal relapse, and other 2 (7.4%) developed distant failure. SUVmax was significantly correlated with progression (p = 0.08, optimal cut-off point SUVmax > 5.1). PFS was significantly influenced by pretreatment SUVmax (SUVmax > 5.1 vs. SUVmax ≤ 5.1; p = 0.012) and T stage (T1 vs. T2-3; p = 0.012). CONCLUSION: SUVmax at pre-treatment FDG PET/CT demonstrated a predictive value for PFS after SBRT for lung cancer.

The Benefit of Post-Mastectomy Radiotherapy in ypN0 Patients after Neoadjuvant Chemotherapy According to Molecular Subtypes / 한국유방암학회지

PURPOSE: The benefit of post-mastectomy radiation therapy (PMRT) in patients with breast cancer who achieve ypN0 following neoadjuvant chemotherapy (NAC) has not yet been established. This study aimed to identify the role of PMRT in patients who achieve ypN0 according to molecular subtype. METHODS: We identified patients initially suspected with axillary disease who achieved ypN0 following NAC. From 13 institutions of the Korean Radiation Oncology Group between 2005 and 2011, a total of 189 patients were included in the analysis. Effects of PMRT on loco-regional control (LRC), disease-free survival (DFS), and overall survival (OS) were evaluated for different molecular subtypes. RESULTS: In all patients, the prognostic effect of PMRT on LRC, DFS, or OS was not significant. Subgroups analysis showed that the effect of PMRT on LRC was different according to molecular subtype (p for interaction = 0.019). PMRT was associated with greater LRC in the luminal subtype (p = 0.046), but not in other subtypes. CONCLUSION: In patients who achieve ypN0 following NAC and mastectomy, PMRT shows no additional survival benefits for any molecular subtype.

Consensus guidelines for the definition of the end stage of disease and last days of life and criteria for medical judgment

In Korea, the Hospice, Palliative Care, and Life-sustaining Treatment Decision-making Act was enacted in February 2016 in order to ensure that the patient's self-determination in end-of-life care processes is respected. To enhance physicians' understanding of this act and to provide proper criteria for medical judgment in variety of clinical settings, consensus guidelines were published in November 2016. In this article, the characteristics of these guidelines and related issues regarding the definitions of ‘the end stage of disease’ and ‘last days of life’ and the criteria for medical judgment are presented and summarized. According to the guidelines, the term ‘end stage of disease’ refers to a state in which there is no possibility of a fundamental recovery and the symptoms are expected to worsen within months. The terms ‘the last days of life’ and ‘the final days of life’ refer to a state in which, despite treatment, the patient's condition is worsening and death is impending, with no possibility of recovery. The attending physician and another relevant specialist should both judge a patient's medical condition as either ‘end stage of disease’ for hospice/palliative care or ‘the last days of life’ for dying patient care according to the law. Caregivers should provide appropriate medical information to eligible patients for palliative or ‘end stage of disease’ care through advance care planning. Therefore, it is critically necessary that caregivers understand the legitimate process of hospice/palliative and dying patient care based on the patient's wishes and best interests. Physicians should apply these consensus guidelines to eligible patients considering their clinical course and the patients' wishes.

Consensus guidelines for the definition of the end stage of disease and last days of life and criteria for medical judgment

In Korea, the Hospice, Palliative Care, and Life-sustaining Treatment Decision-making Act was enacted in February 2016 in order to ensure that the patient's self-determination in end-of-life care processes is respected. To enhance physicians' understanding of this act and to provide proper criteria for medical judgment in variety of clinical settings, consensus guidelines were published in November 2016. In this article, the characteristics of these guidelines and related issues regarding the definitions of ‘the end stage of disease’ and ‘last days of life’ and the criteria for medical judgment are presented and summarized. According to the guidelines, the term ‘end stage of disease’ refers to a state in which there is no possibility of a fundamental recovery and the symptoms are expected to worsen within months. The terms ‘the last days of life’ and ‘the final days of life’ refer to a state in which, despite treatment, the patient's condition is worsening and death is impending, with no possibility of recovery. The attending physician and another relevant specialist should both judge a patient's medical condition as either ‘end stage of disease’ for hospice/palliative care or ‘the last days of life’ for dying patient care according to the law. Caregivers should provide appropriate medical information to eligible patients for palliative or ‘end stage of disease’ care through advance care planning. Therefore, it is critically necessary that caregivers understand the legitimate process of hospice/palliative and dying patient care based on the patient's wishes and best interests. Physicians should apply these consensus guidelines to eligible patients considering their clinical course and the patients' wishes.

Is trehalose an autophagic inducer? Unraveling the roles of non-reducing disaccharides on autophagic flux and alpha-synuclein aggregation.

Autophagy is a pivotal intracellular process by which cellular macromolecules are degraded upon various stimuli. A failure in the degradation of autophagic substrates such as impaired organelles and protein aggregates leads to their accumulations, which are characteristics of many neurodegenerative diseases. Pharmacological activation of autophagy has thus been considered a prospective therapeutic approach for treating neurodegenerative diseases. Among a number of autophagy-inducing agents, trehalose has received attention for its beneficial effects in different disease models of neurodegeneration. However, how trehalose promotes autophagy has not been fully revealed. We investigated the influence of trehalose and other disaccharides upon autophagic flux and aggregation of α-synuclein, a protein linked to Parkinson's disease. In differentiated human neuroblastoma and primary rat cortical neuron culture models, treatment with trehalose and other disaccharides resulted in accumulation of lipidated LC3 (LC3-II), p62, and autophagosomes, whereas it decreased autolysosomes. On the other hand, addition of Bafilomycin A1 to trehalose treatments had relatively marginal effect, an indicative of autophagic flux blockage. In concordance with these results, the cells treated with trehalose exhibited an incremental tendency in α-synuclein aggregation. Secretion of α-synuclein was also elevated in the culture medium upon trehalose treatment, thereby significantly increasing intercellular transmission of this protein. Despite the substantial increase in α-synuclein aggregation, which normally leads to cell death, cell viability was not affected upon treatment with trehalose, suggesting an autophagy-independent protective function of trehalose against protein aggregates. This study demonstrates that, although trehalose has been widely considered an autophagic inducer, it may be actually a potent blocker of the autophagic flux.

Difference in Tumor Area as a Predictor of a Pathological Complete Response for Patients With Locally Advanced Rectal Cancer

PURPOSE: This study was conducted to discover the clinical factors that can predict pathologically complete remission (pCR) after neoadjuvant chemoradiotherapy (CRT), so that those factors may help in deciding on a treatment program for patients with locally advanced rectal cancer. METHODS: A total of 137 patients with locally advanced rectal cancer were retrospectively enrolled in this study, and data were collected retrospectively. The patients had undergone a total mesorectal excision after neoadjuvant CRT. Histologic response was categorized as pCR vs. non-pCR. The tumor area was defined as (tumor length) × (maximum tumor depth). The difference in tumor area was defined as pre-CRT tumor area – post-CRT tumor area. Univariate and multivariate logistic regression analyses were conducted to find the factors affecting pCR. A P-value < 0.05 was considered significant. RESULTS: Twenty-three patients (16.8%) achieved pCR. On the univariate analysis, endoscopic tumor circumferential rate <50%, low pre-CRT T & N stage, low post-CRT T & N stage, small pretreatment tumor area, and large difference in tumor area before and after neoadjuvant CRT were predictive factors of pCR. A multivariate analysis found that only the difference in tumor area before and after neoadjuvant CRT was an independent predictor of pCR (P < 0.001). CONCLUSION: The difference in tumor area, as determined using radiologic tools, before and after neoadjuvant CRT may be important predictor of pCR. This clinical factor may help surgeons to determine which patients who received neoadjuvant CRT for locally advanced rectal cancer should undergo surgery.

Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy

PURPOSE: This study aimed to assess the effects of body mass index (BMI) on survival in cervical cancer patients who had undergone surgery and radiotherapy (RT). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 70 cervical cancer patients who underwent surgery and RT from 2007 to 2012. Among them, 40 patients (57.1%) had pelvic lymph node metastases at the time of diagnosis. Sixty-seven patients (95.7%) had received chemotherapy. All patients had undergone surgery and postoperative RT. Median BMI of patients was 22.8 kg/m² (range, 17.7 to 35.9 kg/m²). RESULTS: The median duration of follow-up was 52.3 months (range, 16 to 107 months). Twenty-four patients (34.3%) showed recurrence. Local failure, regional lymph nodal failure, and distant failure occurred in 4 (5.7%), 6 (8.6%), and 17 (24.3%) patients, respectively. The 5-year actuarial pelvic control rate was 83.4%. The 5-year cancer-specific survival (CSS) and disease-free survival (DFS) rates were 85.1% and 65.0%, respectively. The presence of pelvic lymph node metastases (n = 30) and being overweight or obese (n = 34, BMI ≥ 23 kg/m²) were poor prognostic factors for CSS (p = 0.003 and p = 0.045, respectively). Of these, pelvic lymph node metastasis was an independent prognostic factor (p = 0.030) for CSS. CONCLUSION: Overweight or obese cervical cancer patients showed poorer survival outcomes than normal weight or underweight patients. Weight control seems to be important in cervical cancer patients to improve clinical outcomes.

Correlation of Molecular Subtypes of Invasive Ductal Carcinoma of Breast with Glucose Metabolism in FDG PET/CT: Based on the Recommendations of the St. Gallen Consensus Meeting 2013 / 대한핵의학회잡지

PURPOSE: This study aimed to investigate the relationship between the SUVmax of primary breast cancer lesions and the molecular subtypes based on the recommendations of the St. Gallen consensus meeting 2013.METHODS: Clinical records of patients who underwent F-18 FDG PET/CT for initial staging of invasive ductal carcinoma (IDC) of SUVmax was correlated with the molecular subtypes defined by the St. Gallen Consensus Meeting 2013, i.e., luminal A-like (LA), luminal B-like HER2 negative (LBHER2−), luminal Blike HER2 positive (LBHER2+), HER2 positive (HER2+), and triple negative (TN), and with the clinicohistopathologic characteristics.RESULTS: The molecular subtype was LA in 38 patients, LBHER2− in 72, LBHER2+ in 21, HER2+ in 30, and TN in 22. The mean SUVmax in the LA, LBHER2−, LBHER2+, HER2+, and TN groups were 4.5 ± 2.3, 7.2 ± 4.9, 7.2 ± 4.3, 10.2 ± 5.5, and 8.8 ± 7.1, respectively. Although SUVmax differed significantly among these subtypes (p < 0.001), the values showed a wide overlap. Optimal cut-off SUVmax to differentiate LA from LBHER2−, LBHER2+, HER2+ and TN were 5.9, 5.8, 7.5, and 10.2 respectively, with area under curve (AUC) of 0.648, 0.709, 0.833, and 0.697 respectively. The cut-off value of 5.9 yielded the highest accuracy for differentiation between the LA and non-LA subtypes, with sensitivity, specificity, and AUC of 79.4 %, 57.9 %, and 0.704 respectively.CONCLUSION: The SUVmax showed a significant correlation with the molecular subtype. Although SUVmax measurements could be used along with immunohistochemical analysis for differentiating between molecular subtypes, its application to individual patients may be limited due to the wide overlaps in SUVmax.

Cell-to-cell Transmission of Polyglutamine Aggregates in C. elegans

Huntington disease (HD) is an inherited neurodegenerative disorder characterized by motor and cognitive dysfunction caused by expansion of polyglutamine (polyQ) repeat in exon 1 of huntingtin (HTT). In patients, the number of glutamine residues in polyQ tracts are over 35, and it is correlated with age of onset, severity, and disease progression. Expansion of polyQ increases the propensity for HTT protein aggregation, process known to be implicated in neurodegeneration. These pathological aggregates can be transmitted from neuron to another neuron, and this process may explain the pathological spreading of polyQ aggregates. Here, we developed an in vivo model for studying transmission of polyQ aggregates in a highly quantitative manner in real time. HTT exon 1 with expanded polyQ was fused with either N-terminal or C-terminal fragments of Venus fluorescence protein and expressed in pharyngeal muscles and associated neurons, respectively, of C. elegans. Transmission of polyQ proteins was detected using bimolecular fluorescence complementation (BiFC). Mutant polyQ (Q97) was transmitted much more efficiently than wild type polyQ (Q25) and forms numerous inclusion bodies as well. The transmission of Q97 was gradually increased with aging of animal. The animals with polyQ transmission exhibited degenerative phenotypes, such as nerve degeneration, impaired pharyngeal pumping behavior, and reduced life span. The C. elegans model presented here would be a useful in vivo model system for the study of polyQ aggregate propagation and might be applied to the screening of genetic and chemical modifiers of the propagation.

Lymphovascular invasion as a negative prognostic factor for triple-negative breast cancer after surgery

PURPOSE: This study aimed to evaluate the prognostic effects of lymphovascular invasion (LVI) in triple-negative breast cancer (TNBC) patients who underwent surgical resection. MATERIALS AND METHODS: A total of 63 non-metastatic TNBC patients who underwent surgical resection were retrospectively investigated from 2007 to 2016 in Inje University Busan Paik Hospital. Pathological tests revealed that 12 patients (19.0%) had LVI. Approximately 61.9% (n = 39) of the patients’ samples stained positive for p53. Additional chemotherapy and radiotherapy (RT) were performed in 53 (84.1%) and 47 (74.6%) patients, respectively. RESULTS: The median follow-up period was 39.5 months (range, 5.9 to 123.0 months). The pathological T stage (p = 0.008), N stage (p = 0.014), and p53 positivity (p = 0.044) were associated with LVI. Overall, the 3-year disease-free survival (DFS) rate and overall survival (OS) rate were 85.4% and 90.2%, respectively. Ten patients (15.9%) experienced relapse. LVI (n = 12) was associated with relapses (p = 0.016). p53 positivity was correlated with poor DFS (p = 0.048). Furthermore, LVI was related to poor DFS (p = 0.011) and OS (p = 0.001) and considered as an independent prognostic factor for DFS (p = 0.039). The 3-year DFS of patients with LVI (n = 12) was only 58.3%. Adjuvant RT minimized the negative prognostic effect of LVI on DFS (p = 0.068 [with RT] vs. p = 0.011 [without RT]). CONCLUSION: LVI was related to the detrimental effects of disease progression and survival of TNBC patients. Thus, a more effective treatment strategy is needed for TNBC patients with LVI.

Correction: Adverse effect of excess body weight on survival in cervical cancer patients after surgery and radiotherapy

The authors noticed that the original version of this paper contains typographical error in Fig. 2.