Increased risk of contralateral breast cancer for BRCA1/2 wild-type, high-risk Korean breast cancer patients: a retrospective cohort study.

BACKGROUND: This study aimed to investigate the contralateral breast cancer (CBC) recurrence rate in Korean breast cancer patients according to their BRCA1/2 germline mutation status, focusing particularly on the CBC recurrence risk in BRCA1/2 negative (BRCAx) patients. METHODS: We conducted a retrospective study on 13,107 primary breast cancer patients. The patients were divided into high-risk and low-risk groups for hereditary breast cancer based on the Korean National Health Insurance Service's eligibility criteria for BRCA1/2 germline mutation testing. The high-risk group was further categorized into the BRCA mutation group, the BRCAx group, and the not tested group. We evaluated the overall survival and cumulative risk of developing CBC in these patients. RESULTS: Among 4494 high-risk patients, 973 (21.7%) underwent genetic testing for BRCA1/2 germline mutation, revealing mutations in 158 patients (16.2%). We observed significant overall survival differences across all four groups, with the high-risk, not-tested group demonstrating notably worse overall survival (p < 0.001). However, when adjusted for other prognostic factors, there was no significant differences in hazard ratio of death between the four groups. The cumulative risk of CBC also varied among the groups. Patients with BRCA1/2 mutations showed a 7.3-fold increased risk of CBC compared to the low-risk group (95% CI 4.11-13.0, p < 0.001). Interestingly, BRCAx patients also demonstrated a significantly higher risk of CBC (HR 2.77, 95% CI 1.76-4.35, p < 0.001). The prognostic importance of the BRCAx for CBC recurrence persisted after adjusting for the age and subtype, but became insignificant when the family history of breast cancer was adjusted. CONCLUSION: Breast cancer patients who are at high risk of hereditary breast cancer but with wild-type BRCA 1/2 genes (BRCAx) have increased risk of developing contralateral breast cancer when compared to the low-risk patients. More careful surveillance and follow-up can be offered to these patients especially when they have family history of breast cancer.

Comparison of long-term oncologic outcomes of central lumpectomy and conventional breast-conserving surgery for invasive breast cancer: propensity score matching analysis.

PURPOSE: Central lumpectomy (CL) is a breast-conserving surgical (BCS) technique that involves excision of the nipple-areolar complex with breast tumor in centrally located breast cancers. We aimed to investigate the long-term clinical outcomes of CL in comparison with conventional BCS (cBCS). METHODS: Patient records who underwent BCS with clear resection margins for invasive breast cancer between 2004 and 2018 were retrospectively reviewed. Of the total 6,533 patients, 106 (1.6%) underwent CL. Median follow-up duration was 73.4 months. 1:3 propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to minimize selection bias. RESULTS: The CL group showed a significantly higher ipsilateral breast tumor recurrence (IBTR) rate than the cBCS group (10-year IBTR rate: 5.8% vs. 3.1%, p = 0.004), even after adjusting for other variables (hazard ratio (HR), 2.65; 95% confidence interval (CI), 1.07-6.60, p = 0.048). However, there were no significant differences observed in regional recurrence, distant metastasis, or overall survival rates between the two groups. Both PSM and IPTW analyses showed significantly higher IBTR in the CL group (PSM HR, 3.27; 95% CI, 0.94-11.36; p = 0.048 and IPTW HR, 4.66; 95%CI, 1.85-11.77; p < 0.001). Lastly, when analyzing 2,213 patients whose tumors were located within 3 cm of the nipple, the CL group showed a significantly higher IBTR than the cBCS group before and after PSM. CONCLUSION: CL was associated with a higher rate of IBTR compared to cBCS, while other survival outcomes were comparable. For centrally located tumors, CL may be considered for patients preferring breast preservation. However, higher risk for IBTR should be informed and careful surveillance may be necessary during the early post-operative follow-up periods.

Survival After Contralateral Axillary Metastasis in Breast Cancer.

BACKGROUND: Despite stage IV categorization, survival outcomes for breast cancer patients who experience contralateral axillary lymph node metastasis (CAM) remain uncertain. This study aimed to investigate the clinical outcomes for patients with metachronous CAM to provide insights into its prognosis and treatment recommendations. METHODS: This study retrospectively reviewed medical records of patients who underwent curative surgery for breast cancer and experienced CAM as the first site of distant metastasis (DM) during the follow-up period between January 2001 and April 2023. Survival outcomes of the CAM patients were compared with those of breast cancer patients with other DM via propensity score-matching (PSM). RESULTS: The study identified 40 breast cancer patients with metachronous CAM. The estimated 5-year overall survival (OS) was 39.6%, and the progression-free survival was 39.4%. The patients with CAM exhibited marginally better OS than the patients with DM (p = 0.071), but survival similar to that of the patients with isolated supraclavicular node recurrence (SCN) (p = 0.509). Moreover, matching of CAM with DM using two PSM models showed a consistently insignificant survival difference (hazard ratio [HR], 1.47; p = 0.124 vs. HR, 1.19; p = 0.542). Ipsilateral breast tumor recurrences (IBTRs) were experienced by 12 patients before or concurrently with the CAM. These patients exhibited significantly better survival than the remaining patients (HR, 0.28; p = 0.024). CONCLUSION: The breast cancer patients with CAM showed survival similar to that for the patients with DM, supporting the current stage IV classification of the CAM. However, CAM associated with IBTR exhibited superior survival outcomes, suggesting that this subset of CAM may benefit from treatments with curative intent.

Oncological Safety of Skipping Axillary Lymph Node Dissection in Patients with Clinical N0, Sentinel Node-Positive Breast Cancer Undergoing Total Mastectomy.

OBJECTIVE: This study aimed to determine whether sentinel lymph node biopsy (SLNB) alone could afford oncological outcomes comparable with axillary lymph node dissection (ALND) in patients with early breast cancer without palpable lymphadenopathy who underwent total mastectomy (TM) and were SLN-positive. METHODS: This study analyzed clinical data of 6747 patients with breast cancer who underwent TM between 2014 and 2018 in two tertiary hospitals in Korea. Overall, 643 clinical stage T1-3 N0 patients who did not receive neoadjuvant therapy and had one to two metastatic SLNs at the time of surgery were included. Propensity score matching was performed between the SLNB alone and ALND groups, adjusting for clinical T stage and number of metastatic SLNs. In total, 237 patients were allocated to each group. RESULTS: Mean number of metastatic SLNs was 1.2 for the SLNB group and 1.6 for the ALND group. With a median follow-up of 65.0 months, 5 year disease-free survival was 90.8% for the SLNB group and 93.9% for the ALND group (hazard ratio [HR] 1.35, 95% confidence interval [CI] 0.70-2.58; p = 0.36). 5 year ipsilateral locoregional recurrence-free survival (LRRFS) was not significantly different between the two groups (95.1% and 98.3% for the SLNB and ALND groups, respectively) [HR 1.86, 95% CI 0.69-5.04; p = 0.21]. In the SLNB group, patients who received radiation therapy (RT) showed superior 5 year LRRFS than patients who did not receive RT (100% vs. 92.9%; p = 0.02). CONCLUSION: Collectively, our findings suggest that SLNB could afford comparable outcomes to ALND in patients with early breast cancer and one to two metastatic SLNs who underwent TM. Importantly, RT could decrease locoregional recurrence in patients who underwent SLNB alone.

Association between estimated glucose disposal rate and subclinical coronary atherosclerosis.

BACKGROUND AND AIMS: The estimated glucose disposal rate (eGDR) is an easily accessible clinical parameter for assessing insulin resistance in patients with diabetes mellitus. In this study, we aimed to investigate the link between eGDR and subclinical coronary atherosclerosis in an asymptomatic middle-aged Korean population. METHODS AND RESULTS: This study involved 4004 subjects who underwent routine health checkups with coronary multidetector computed tomography (MDCT) at Asan Medical Center from 2007 to 2011, among whom 913 had a follow-up analysis through 2014. The eGDR was calculated using: 21.16 - (0.09 ∗ waist circumference [cm]) - (3.41 ∗ hypertension) - (0.55 ∗ glycated hemoglobin [%]). Patients were categorized into three groups according to the tertiles of eGDR. Subclinical coronary atherosclerosis was defined by significant coronary stenosis (≥50%), presence of plaques, coronary artery calcification (CAC) score, and its progression. As a result, a lower eGDR level was associated with higher prevalence of significant coronary stenosis, plaques, moderate to severe CAC, and CAC progression. Compared to other markers or risk scores, eGDR was superior to other biomarkers of insulin resistance but did not provide additional information beyond classic cardiovascular risk models like the Framingham Risk Score and Pooled Cohort Equations. CONCLUSION: Decreased eGDR values were significantly associated with higher subclinical coronary atherosclerosis burdens in an asymptomatic middle-aged Korean population. However, its clinical implications remain uncertain due to its weaker performance compared to established cardiovascular risk models.

Association between metformin use and the risk of developing open-angle glaucoma among patients with diabetes: a retrospective cohort study and meta-analysis.

PURPOSE: Recent studies examining the neuroprotective effects of metformin on open-angle glaucoma (OAG) have failed to provide consistent results. In this study, we investigated the association between metformin use and OAG. METHODS: Data were obtained from a sample cohort of the Korean National Health Insurance database. Patients diagnosed with type-2 diabetes (T2DM) between 2004 and 2013 were included. We performed propensity score-matched analysis in a matched cohort (N = 20,646). The risk of the newly developed OAG was estimated using a Cox proportional hazards model. Including the present study, the meta-analysis included five studies to calculate the pooled risk for OAG based on metformin use. RESULTS: In the adjusted model, the analysis revealed no statistical association between metformin use and OAG incidence (hazard ratio [HR] 1.05; 95% confidence interval [CI] 0.79-1.40; P = 0.738). The highest tercile of metformin use demonstrated no statistical significance (HR 0.93 [95% CI 0.63-1.37]; P = 0.703). No significant dose-dependent association was observed between the cumulative dose and incidence of OAG (P-value for trend = 0.336). In a meta-analysis of four published articles and the present study, the common-effects and random-effects models indicated conflicting results in terms of significance. The random effects model demonstrated no significant association (pooled risk ratio 0.53; 95% CI 0.24-1.19; P = 0.123). CONCLUSION: We found no significant association between metformin use and OAG incidence in patients with T2DM in this population-based cohort study and meta-analysis. Further studies are needed to investigate the association between metformin use and the risk of OAG among patients with T2DM.

A Survey of Practice Patterns for Clinical Nodal Staging Prior to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The importance of clinical staging in breast cancer has increased owing to the wide use of neoadjuvant systemic therapy (NST). This study aimed to investigate the current practice patterns regarding clinical nodal staging in breast cancer in real-world settings. MATERIALS AND METHODS: A web-based survey was administered to board-certified oncologists in Korea, including breast surgical, medical, and radiation oncologists, from January to April 2022. The survey included 19 general questions and 4 case-based questions. RESULTS: In total, 122 oncologists (45 radiation, 44 surgical, and 33 medical oncologists) completed the survey. Among them, 108 (88%) responded that clinical staging before NST was primarily performed by breast surgeons. All the respondents referred to imaging studies during nodal staging. Overall, 64 (52.5%) responders determined the stage strictly based on the radiology reports, whereas 58 (47.5%) made their own decision while noting radiology reports. Of those who made their own decisions, 88% referred to the number or size of the suspicious node. Of the 75 respondents involved in prescribing regimens for neoadjuvant chemotherapy, 58 (77.3%) responded that the reimbursement regulations in the selection of NST regimens affected nodal staging in clinical practice. In the case-based questions, high variability was observed among the clinicians in the same cases. CONCLUSIONS: Diverse assessments by specialists owing to the lack of a clear, harmonized staging system for the clinical nodal staging of breast cancer can lead to diverse practice patterns. Thus, practical, harmonized, and objective methods for clinical nodal staging and for the outcomes of post-NST response are warranted for appropriate treatment decisions and accurate outcome evaluation.

Use of imaging prediction model for omission of axillary surgery in early-stage breast cancer patients.

PURPOSE: To develop a prediction model incorporating clinicopathological information, US, and MRI to diagnose axillary lymph node (LN) metastasis with acceptable false negative rate (FNR) in patients with early stage, clinically node-negative breast cancers. METHODS: In this single center retrospective study, the inclusion criteria comprised women with clinical T1 or T2 and N0 breast cancers who underwent preoperative US and MRI between January 2017 and July 2018. Patients were temporally divided into the development and validation cohorts. Clinicopathological information, US, and MRI findings were collected. Two prediction models (US model and combined US and MRI model) were created using logistic regression analysis from the development cohort. FNRs of the two models were compared using the McNemar test. RESULTS: A total of 964 women comprised the development (603 women, 54 ± 11 years) and validation (361 women, 53 ± 10 years) cohorts with 107 (18%) and 77 (21%) axillary LN metastases in each cohort, respectively. The US model consisted of tumor size and morphology of LN on US. The combined US and MRI model consisted of asymmetry of LN number, long diameter of LN, tumor type, and multiplicity of breast cancers on MRI, in addition to tumor size and morphology of LN on US. The combined model showed significantly lower FNR than the US model in both development (5% vs. 32%, P < .001) and validation (9% vs. 35%, P < .001) cohorts. CONCLUSION: Our prediction model combining US and MRI characteristics of index cancer and LN lowered FNR compared to using US alone, and could potentially lead to avoid unnecessary SLNB in early stage, clinically node-negative breast cancers.

Clinical significance of HER2-low expression in early breast cancer: a nationwide study from the Korean Breast Cancer Society.

BACKGROUND: There is an increasing interest in HER2-low breast cancer with promising data from clinical trials using novel anti-HER2 antibody-drug conjugates. We explored the differences in clinicopathological characteristics and survival outcomes between HER2-low and HER2-IHC 0 breast cancer. METHODS: Using nationwide data from the Korean Breast Cancer Registry between 2006 and 2011, 30,491 patients with stages I to III breast cancer were included in the analysis: 9,506 (31.2%) in the HER2-low group and 20,985 (68.8%) in the HER2-IHC 0 group. Kaplan-Meier and Cox proportional hazards regression survival analysis were used to compare breast cancer-specific survival between the two groups. RESULTS: HER2-low breast cancer was more frequent in patients with hormone receptor-positive breast cancer than in those with triple-negative breast cancer. In patients with hormone receptor-positive breast cancer, HER2-low breast cancer was associated with fewer T4 tumors, higher histological grade, and a negative lymphatic invasion. In patients with triple-negative breast cancer, HER2-low breast cancer was associated with a high lymph node ratio and positive lymphatic invasion. HER2-low breast cancer was significantly associated with a lower Ki-67 labeling index. No significant difference was observed in overall survival between the two groups. HER2-low breast cancer showed significantly better breast cancer-specific survival than HER2-IHC 0 breast cancer, regardless of the hormone receptor status. In multivariate analysis, the impact of low HER2 expression on breast cancer-specific survival was significant only in triple-negative breast cancer (HRs, 0.68; 95% CI, 0.49-0.93; P = 0.019). CONCLUSIONS: These findings suggest that the biology and clinical impact of low HER2 expression can differ according to the hormone receptor status and support the need for further investigation on the understanding of the biology of HER2-low breast cancer.

Diagnostic performance improvement with combined use of proteomics biomarker assay and breast ultrasound.

PURPOSE: To investigate the combined use of blood-based 3-protein signature and breast ultrasound (US) for validating US-detected lesions. METHODS: From July 2011 to April 2020, women who underwent whole-breast US within at least 6 months from sampling period were retrospectively included. Blood-based 3-protein signature (Mastocheck®) value and US findings were evaluated. Following outcome measures were compared between US alone and the combination of Mastocheck® value with US: sensitivity, specificity, positive predictive value (PPV), negative predictive value, area under the receiver operating characteristic curve (AUC), and biopsy rate. RESULTS: Among the 237 women included, 59 (24.9%) were healthy individuals and 178 (75.1%) cancer patients. Mean size of cancers was 1.2 ± 0.8 cm. Median value of Mastocheck® was significantly different between nonmalignant (- 0.24, interquartile range [IQR] - 0.48, - 0.03) and malignant lesions (0.55, IQR - 0.03, 1.42) (P < .001). Utilizing Mastocheck® value with US increased the AUC from 0.67 (95% confidence interval [CI] 0.61, 0.73) to 0.81 (95% CI 0.75, 0.88; P < .001), and specificity from 35.6 (95% CI 23.4, 47.8) to 64.4% (95% CI 52.2, 76.6; P < .001) without loss in sensitivity. PPV was increased from 82.2 (95% CI 77.1, 87.3) to 89.3% (95% CI 85.0, 93.6; P < .001), and biopsy rate was significantly decreased from 79.3 (188/237) to 72.1% (171/237) (P < .001). Consistent improvements in specificity, PPV, and AUC were observed in asymptomatic women, in women with dense breast, and in those with normal/benign mammographic findings. CONCLUSION: Mastocheck® is an effective tool that can be used with US to improve diagnostic specificity and reduce false-positive findings and unnecessary biopsies.

Surgical margin status and survival outcomes of breast cancer patients treated with breast-conserving surgery and whole-breast irradiation after neoadjuvant chemotherapy.

PURPOSE: The definition of "no tumor on ink" is generally applied for clear resection margin (RM) after breast-conserving surgery (BCS). However, few studies reported the effect of RM in the setting of neoadjuvant chemotherapy (NAC). We investigated the association between RM status and survival outcomes for those who underwent BCS after NAC for breast cancer. METHODS: We retrospectively reviewed the data of 2,803 patients who underwent BCS and whole-breast irradiation after NAC between January 2008 and December 2016 from three institutions in South Korea. RESULTS: The 786 patients in the pathologic complete response group (RpCR) had significantly longer local recurrence-free survival (LRFS) than the 1,949 patients in clear or close RM and non-pCR group (R0) and the 68 patients in involved RM and non-pCR group (R1) (vs. R0, p = 0.001; vs. R1, p = 0.049). Patients in R0 showed no benefit in LRFS compared to R1 on both log-rank test (HR = 1.20; 95% C.I., 0.49-2.93; p = 0.692) and Cox regression analysis (HR = 2.05; 95% C.I., 0.64-6.58; p = 0.227). Subgroup analysis according to tumor subtypes revealed that there was no significant difference in LRFS, distant metastasis-free survival, and recurrence-free survival between the R0 and R1 group. Additionally, among 286 patients with pCR with residual ductal carcinoma in situ (DCIS) alone, RM status was not significantly associated with LRFS. CONCLUSION: Clear RM of specimen does not have benefit on LRFS after NAC. Additionally, for the patients showing pCR with residual DCIS in the breast, margin involvement also did not affect the risk of local recurrence.

Association between type 2 diabetes and skeletal muscle quality assessed by abdominal computed tomography scan.

AIM: To examine the association between type 2 diabetes and the amount and quality of trunk muscle as assessed by computed tomography (CT) scan. MATERIALS AND METHODS: A total of 20,986 subjects (13,007 men and 7979 women) who underwent abdominal CT scan as part of a routine health check-up were included. The total abdominal muscle area (TAMA) measured at the third lumbar vertebrae was classified into skeletal muscle area (SMA), and intermuscular adipose tissue area. SMA was divided into good quality muscles (normal attenuation muscle area [NAMA]) and poor quality muscles (low attenuation muscle area). NAMA/TAMA index was calculated. RESULTS: Subjects with type 2 diabetes had higher values of TAMA and SMA but significantly lower values of NAMA and NAMA/TAMA index. Compared with those in the lowest quartile of NAMA/TAMA index, subjects in the highest quartile had metabolically favourable laboratory findings, a lower prevalence of type 2 diabetes (Q1 vs. Q4: 19.3% vs. 9.5% in men, 12.3% vs. 3.0% in women) and inverse association with type 2 diabetes (odds ratio for Q2, Q3, and Q4: 0.87, 0.78, and 0.75 in men; 0.82, 0.70, and 0.68 in women) after multivariable adjustment. CONCLUSIONS: The amount of good quality muscle on CT scan was associated with a lower prevalence of type 2 diabetes.

Association Between Muscle Quality Measured by Abdominal Computed Tomography and Subclinical Coronary Atherosclerosis.

OBJECTIVE: Low muscle mass was known to be associated with cardiovascular diseases. However, only few studies investigated the association between muscle quality and subclinical coronary atherosclerosis. Thus, we evaluated whether muscle quality measured by abdominal computed tomography is associated with the risk of coronary artery calcification. Approach and Results: We conducted a cross-sectional study on 4068 subjects without cardiovascular disease who underwent abdominal and coronary computed tomography between 2012 and 2013 during health examinations. The cross-sectional area of the skeletal muscle was measured at the L3 level (total abdominal muscle area) and segmented into normal attenuation muscle area, low attenuation muscle area, and intramuscular adipose tissue. We calculated the normal attenuation muscle area/total abdominal muscle area index, of which a higher value reflected a higher proportion of good quality muscle (normal attenuation muscle area) and a lower proportion of myosteatosis (low attenuation muscle area and intramuscular adipose tissue). In women, as the normal attenuation muscle area/total abdominal muscle area quartiles increased, the odds ratios (95% CIs) for significant coronary artery calcification (>100) consistently decreased (0.44 [0.24-0.80], 0.39 [0.19-0.81], 0.34 [0.12-0.98]; P=0.003) after adjusting for cardiovascular risk factors including visceral fat area and insulin resistance. In men, the odds ratios in the Q2 group were significantly lower than those in the Q1, but the association was attenuated in Q3-4 after adjustment. CONCLUSIONS: A higher proportion of good quality muscle was strongly associated with a lower prevalence of significant coronary artery calcification after adjustment, especially in women. Poor skeletal muscle quality may be an important risk factor for subclinical coronary atherosclerosis.

Machine learning predicting myopic regression after corneal refractive surgery using preoperative data and fundus photography.

PURPOSE: Myopic regression after surgery is the most common long-term complication of refractive surgery, but it is difficult to identify myopic regression without long-term observation. This study aimed to develop machine learning models to identify high-risk patients for refractive regression based on preoperative data and fundus photography. METHODS: This retrospective study assigned subjects to the training (n = 1606 eyes) and validation (n = 403 eyes) datasets with chronological data splitting. Machine learning models with ResNet50 (for image analysis) and XGBoost (for integration of all variables and fundus photography) were developed based on subjects who underwent corneal refractive surgery. The primary outcome was the predictive performance for the presence of myopic regression at 4 years of follow-up examination postoperatively. RESULTS: By integrating all factors and fundus photography, the final combined machine learning model showed good performance to predict myopic regression of more than 0.5 D (area under the receiver operating characteristic curve [ROC-AUC], 0.753; 95% confidence interval [CI], 0.710-0.793). The performance of the final model was better than the single ResNet50 model only using fundus photography (ROC-AUC, 0.673; 95% CI, 0.627-0.716). The top-five most important input features were fundus photography, preoperative anterior chamber depth, planned ablation thickness, age, and preoperative central corneal thickness. CONCLUSION: Our machine learning algorithm provides an efficient strategy to identify high-risk patients with myopic regression without additional labor, cost, and time. Surgeons might benefit from preoperative risk assessment of myopic regression, patient counseling before surgery, and surgical option decisions.

Transoral robotic thyroidectomy versus conventional open thyroidectomy: comparative analysis of surgical outcomes using propensity score matching.

BACKGROUND: Various approaches for thyroid surgery became possible with the use of robotic systems. Transoral robotic thyroidectomy (TORT) is one of the newest approaches and draws attention because of its cosmetic excellence. In this study, we compared the surgical outcomes of TORT and conventional open thyroidectomy (OT). METHODS: We retrospectively reviewed and compared the medical records of consecutive patients who underwent TORT or OT for thyroid carcinoma from March 2009 to January 2018. Propensity score matching using 10 clinico-pathologic factors was used to generate two matched cohorts, each composed of 186 patients. RESULTS: The study included 372 patients who underwent TORT (n = 186) or OT (n = 186). Mean age, tumor size, and gender were not different between both groups. The two groups showed similar surgical outcomes, except for a longer operative time for TORT. There was one patient with immediate postoperative bleeding in the TORT group. The patient underwent re-operation for hemostasis with endoscopic approach. In the OT group, one patient had wound seroma, which was treated by several rounds of needle aspiration without infection. Vocal cord palsy was present in one patient in the TORT group, which was recovered in 3 months. CONCLUSIONS: TORT could be performed safely and had comparable surgical outcomes with OT in the selected patients. TORT may be a suitable operative alternative for patients who do not want to leave scars on the neck.

A Novel Peptide Derived from the Transmembrane Domain of Romo1 Is a Promising Candidate for Sepsis Treatment and Multidrug-Resistant Bacteria.

The emergence of multidrug-resistant (MDR) bacteria through the abuse and long-term use of antibiotics is a serious health problem worldwide. Therefore, novel antimicrobial agents that can cure an infection from MDR bacteria, especially gram-negative bacteria, are urgently needed. Antimicrobial peptides, part of the innate immunity system, have been studied to find bactericidal agents potent against MDR bacteria. However, they have many problems, such as restrained systemic activity and cytotoxicity. In a previous study, we suggested that the K58-R78 domain of Romo1, a mitochondrial protein encoded by the nucleus, was a promising treatment candidate for sepsis caused by MDR bacteria. Here, we performed sequence optimization to enhance the antimicrobial activity of this peptide and named it as AMPR-22 (antimicrobial peptide derived from Romo1). It showed broad-spectrum antimicrobial activity against 17 sepsis-causing bacteria, including MDR strains, by inducing membrane permeabilization. Moreover, treatment with AMPR-22 enabled a remarkable survival rate in mice injected with MDR bacteria in a murine model of sepsis. Based on these results, we suggest that AMPR-22 could be prescribed as a first-line therapy (prior to bacterial identification) for patients diagnosed with sepsis.

CycleGAN-based deep learning technique for artifact reduction in fundus photography.

PURPOSE: A low quality of fundus photograph with artifacts may lead to false diagnosis. Recently, a cycle-consistent generative adversarial network (CycleGAN) has been introduced as a tool to generate images without matching paired images. Therefore, herein, we present a deep learning technique that removes the artifacts automatically in a fundus photograph using a CycleGAN model. METHODS: This study included a total of 2206 anonymized retinal images including 1146 with artifacts and 1060 without artifacts. In this experiment, we applied the CycleGAN model to color fundus photographs with a pixel resolution of 256 × 256 × 3. To apply the CycleGAN to an independent dataset, we randomly divided the data into training (90%) and test (10%) datasets. Additionally, we adopted the automated quality evaluation (AQE) to assess the retinal image quality. RESULTS: From the results, we observed that the artifacts such as overall haze, edge haze, lashes, arcs, and uneven illumination were successfully reduced by the CycleGAN in the generated images, and the main information of the retina was essentially retained. Further, we observed that most of the generated images exhibited improved AQE grade values when compared with the original images with artifacts. CONCLUSION: Thus, we could conclude that the CycleGAN technique can effectively reduce the artifacts and improve the quality of fundus photographs, and it may be beneficial for clinicians in analyzing the low-quality fundus photographs. Future studies should improve the quality and resolution of the generated image to provide a more detailed fundus photography.

Triglyceride glucose index is a useful marker for predicting subclinical coronary artery disease in the absence of traditional risk factors.

BACKGROUND: Atherosclerotic cardiovascular (CV) events commonly occur in individuals with a low CV risk burden. This study evaluated the ability of the triglyceride glucose (TyG) index to predict subclinical coronary artery disease (CAD) in asymptomatic subjects without traditional CV risk factors (CVRFs). METHODS: This retrospective, cross-sectional, and observational study evaluated the association of TyG index with CAD in 1250 (52.8 ± 6.5 years, 46.9% male) asymptomatic individuals without traditional CVRFs (defined as systolic/diastolic blood pressure ≥ 140/90 mmHg; fasting glucose ≥126 mg/dL; total cholesterol ≥240 mg/dL; low-density lipoprotein cholesterol ≥160 mg/dL; high-density lipoprotein cholesterol < 40 mg/dL; body mass index ≥25.0 kg/m2; current smoking; and previous medical history of hypertension, diabetes, or dyslipidemia). CAD was defined as the presence of any coronary plaque on coronary computed tomographic angiography. The participants were divided into three groups based on TyG index tertiles. RESULTS: The prevalence of CAD increased with elevating TyG index tertiles (group I: 14.8% vs. group II: 19.3% vs. group III: 27.6%; P < 0.001). Multivariate logistic regression models showed that TyG index was associated with an increased risk of CAD (odds ratio [OR] 1.473, 95% confidence interval [CI] 1.026-2.166); especially non-calcified (OR 1.581, 95% CI 1.002-2.493) and mixed plaques (OR 2.419, 95% CI 1.051-5.569) (all P < 0.05). The optimal TyG index cut-off for predicting CAD was 8.44 (sensitivity 47.9%; specificity 68.5%; area under the curve 0.600; P < 0.001). The predictive value of this cut-off improved after considering the non-modifiable factors of old age and male sex. CONCLUSIONS: TyG index is an independent marker for predicting subclinical CAD in individuals conventionally considered healthy.

Clinical Experience with Treatment of Aquafilling Filler-Associated Complications: A Retrospective Study of 146 Cases.

BACKGROUND: Aquafilling filler is used for breast and buttock augmentation, which are the most commonly performed cosmetic surgery procedures. However, complications after using Aquafilling filler for breast augmentation have been reported, and there are concerns regarding its use in large areas, such as the buttocks. We provide our experience with complications after breast augmentation and buttock augmentation using Aquafilling filler. METHODS: This observational cohort study analyzed the data of 399 patients treated for filler-related complications at our institutes from September 2015 to November 2019. Of these patients, 146 underwent surgery to remove Aquafilling filler from the breast or buttock. RESULTS: The mean time between Aquafilling filler use and complication onset was 38.5 ± 10.2 months. The average amount of filler material removed from one side of the breast or buttock was 285.5 ± 95.8 mL (range 150-750 mL). The most common complications were induration and masses (83.6%), followed by pain (52.1%), firmness (24.7%), asymmetry (10.3%), migration (8.2%), mastitis (6.8%), dimpling (6.2%), fever (3.4%), and sepsis (n = 1). After treatment, there was no recurrence of infection, and the patient satisfaction level based on the visual analogue scale was 8.0 ± 0.9. CONCLUSIONS: Although Aquafilling filler is easily injectable and has long-term clinical effects, complications can occur. Furthermore, there are concerns regarding its toxicity and influence on the surrounding tissues. Hence, further research studies on Aquafilling filler and evidence regarding its long-term safety are needed. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hepatitis C Virus p7 Induces Membrane Permeabilization by Interacting with Phosphatidylserine.

Hepatitis C virus (HCV) p7 is known to be a nonselective cation channel for HCV maturation. Because the interaction of HCV proteins with host lipids in the endoplasmic reticulum membrane is crucial for the budding process, the identification of p7-lipid interactions could be important for understanding the HCV life cycle. Here, we report that p7 interacts with phosphatidylserine (PS) to induce membrane permeabilization. The interaction of p7 with PS was not inhibited by Gd3+ ions, which have been known to interact with negatively charged lipids, but channel activity and p7-induced mitochondrial depolarization were inhibited by Gd3+ ions. From the present results, we suggest that the p7-PS interaction plays an essential role in regulating its ion channel function and could be a potential molecular target for anti-HCV therapy.