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Postoperative short nose is one of the most difficult problems encountered in plastic surgery. We propose a technique of lining rotation flaps combined with composite chondrocutaneous auricular graft from the triangular fossa to reconstruct the lining defect and improve surgical results.Twenty patients were operated on between 2016 and 2019 for postoperative short nose. Lining rotation flaps were used to supply missing medial mucosal lining with creation of a raw surface at the lateral lining in 10 patients (intervention group). A total of 17 composite chondrocutaneous grafts taken from the triangular fossa of the ears were used to resurface the defect. The other 10 patients received lining management using conventional techniques (control group).There was a near-complete take of 13/17 composite grafts (76.5%), with four partial losses that healed uneventfully. Anthropometric analysis of preop and postop profile photos showed statistically significant decreased nasolabial angle in both groups. The amount of derotation achieved was significantly increased (p 0.05) with our proposed method (Intervention group: 12.3 ± 9.3° vs. control group: 6.55 ± 4.5°). Donor sites healed uneventfully. Both groups of patients were satisfied with their results based on Rhinoplasty Outcomes Evaluation questionnaire.The lining rotation flap with triangular fossa composite graft is a safe and effective method for management of the postoperative short nose in Asians.

This study aimed to propose a novel four-type deformity and treatment-oriented classification of the lower eyelids that directs the therapeutic combination of three-step lower blepharoplasty for Asian populations. We reviewed 183 patients who underwent a therapeutic combination of three steps of lower blepharoplasty after being diagnosed with four types of lower eyelid deformities between July 2018 and April 2021. The three-step lower blepharoplasty includes: (1) mid-face and lower eyelid augmentation, (2) transconjunctival eye bag removal, and (3) skin pinch removal. Consecutive digital images, detailed fat graft volume, fat removal amount, skin pinch removal amount, complications, and patient’s satisfaction and aesthetic improvement score were recorded. The overall patient’s satisfy score is 91. Aesthetic improvement score is 80.2 and 83.3 among lay persons and experts, respectively. The volume of the fat graft ranges from 2 to 3 mL per orbit according to the severity of the deformity. The amount of fat removed was 0.53 ± 0.36 and 0.61 ± 0.40 mL per orbit in types II and III patients, respectively. There is no lower lid malposition. Eleven patients had over-correction of fat grafting, and they need steroid injection; 20 patients had under-correction of fat grafting, and they need secondary fat grafting. Ten patients need secondary skin pinch excision due to post-op skin redundancy. Two patients had conjunctiva wound granuloma. The combination of three-step lower blepharoplasty according to the novel classification is a straightforward and effective method to correct lower eyelid deformities. The complication rate was low with high patient satisfaction. 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 .

BACKGROUND Several materials can serve as spacer grafts in the repair of retracted lower eyelids. However, previous studies did not reveal any of these to be superior to the others. From our perspective, autologous dermal grafts are ideal because they are biologically compatible and abundantly available. However, the absorption of these grafts is an issue, and the thickness of the dermal grafts is crucial. We evaluated the dermal thickness at five potential donor sites using ultrasonography and the efficacy and safety of the posterior neck dermis as a spacer graft in the correction of retracted lower eyelids. METHODS In 20 healthy volunteers, the dermal thickness was assessed using ultrasonography and compared between the posterior neck, upper arm, inguinal area, intergluteal cleft, and gluteal sulcus. Between January 2018 and June 2021, eight retracted lower eyelids in eight patients were repaired using a posterior neck dermal graft. The surgical results of these grafts were also evaluated. RESULTS The mean age of the volunteers was 37.8 years, and the mean body mass index was 24.45 kg/m2. The intergluteal cleft provided the thickest dermis followed by the posterior neck and gluteal sulcus, which were not significantly different. The upper arm and inguinal area had the thinnest dermis without significant differences between them. The mean marginal reflex distance 2/iris ratio decreased by 0.15 (p=0.008). The mean cosmetic score (0-10) for evaluation of lower eyelid reconstruction increased by 3.38 (p=0.011). The mean Vancouver Scar Scale score for evaluation of donor site scarring was 3.21. CONCLUSIONS Although the posterior neck dermis is the second thickest, it is an ideal spacer graft in the reconstruction of retracted lower eyelids. Adequate thickness, uncomplicated methods, and a closer surgical field are its advantages. Additionally, donor site morbidity is minimal, with acceptable scarring. 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 .

The relationship between height and incident atrial fibrillation (AF) has recently been demonstrated. We aimed to evaluate the impact of height on outcomes of ablation in patients with drug-refractory symptomatic paroxysmal AF (PAF). A total of 689 patients (470 males; age, 53.0 ± 11.7 years) with symptomatic paroxysmal AF receiving index catheter ablation (CA) between 2003 and 2013 were enrolled in this study. The baseline characteristics, ablation, and follow-up results were evaluated. The patients were categorized according to the quartiles of height for each sex. Patients in the lower quartiles of height had a lower incidence of AF recurrence (log-rank p = 0.022). Height in female patients was strongly associated with AF recurrence (p = 0.027) after an index ablation in the 6.33 ± 4.32 years of follow-up. Female patients > 159 cm in height had a higher likelihood of AF recurrence after index CA (HR = 2.01, 95% CI: 1.24–3.25, p = 0.005) than that in those below this height. In computed tomography (CT) scan, the superoinferior diameter of the left atrium (LA) correlated with body height in females, but not in male patients. Height is associated with AF recurrence after the index CA of PAF in female patients. In Asian populations, women above height 159 cm are twice as likely to have AF recurrence post-ablation as shorter women.

Acute myeloid leukemia (AML) is an aggressive disease with poor outcomes, overwhelmingly due to relapse. Minimal residual disease (MRD), defined as the persistence of leukemic cells after chemotherapy treatment, is thought to be the major cause of relapse. The origins of relapse in AML have been traced to rare therapy-resistant leukemic stem cells (LSCs) that are already present at diagnosis. Effective treatment strategies for long-term remission are lacking, as it has been difficult to eliminate LSCs with conventional therapy. Here, we proposed a new approach based on the chimeric antigen receptor (CAR)-directed T lymphocytes, targeting T-cell immunoglobulin, and mucin domain 3 (TIM-3) to treat MRD in patients with AML. TIM-3 is selected as the target because it is highly expressed on AML blasts and LSCs in most subtypes regardless of the patient's genetic characteristics and treatment course. Moreover, it is absent in the normal hematopoietic stem cells, granulocytes, naïve lymphocytes, and most normal nonhematopoietic tissues. Using a naïve human Fab phage display library, we isolated an anti-human TIM-3 antibody and designed a second-generation anti–TIM-3. Our anti–TIM-3 CAR T cells exhibit potent antileukemic activity against AML cell lines and primary AML blasts, and in the mouse models. More importantly, we demonstrate efficient killing of the primary LSCs directly isolated from the patients. Hence, eradication of the LSCs present in the MRD by anti–TIM-3 CAR T-cell therapy following the first-line treatment may improve the clinical outcomes of patients with AML.

Introduction The efficacy of stereotactic body radiation therapy (SBRT) as an alternative treatment for recurrent ventricular tachycardia (VT) is still unclear. This study aimed to report the outcome of SBRT in VT patients with nonischemic cardiomyopathy (NICM). Methods The determination of the target substrate for radiation was based on the combination of CMR results and electroanatomical mapping merged with the real-time CT scan image. Radiation therapy was performed by Flattening-filter-free (Truebeam™) system, and afterward, patients were followed-up for 13.5±2.8 months. We analyzed the outcome of death, incidence of recurrent VT, ICD shocks, anti-tachycardia pacing (ATP) sequences, and possible irradiation side-effects. Results A total of 3 cases of NICM patients with anteroseptal scar detected by CMR. SBRT was successfully performed in all patients. During the follow-up, we found that VT recurrences occurred in all patients. In one patient, it happened during a 6-week blanking period, while the others happened afterward. Re-hospitalization due to VT only appeared in one patient. Through ICD interrogation, we found that all patients have reduced VT burden and ATP therapies. All of the patients died during the follow-up period. Radiotherapy-related adverse events did not occur in all patients. Conclusions SBRT therapy reduces the number of VT burden and ATP sequence therapy in NICM patients with VT, which had a failed previous catheter ablation. However, the efficacy and safety aspects, especially in NICM cases, remained unclear. This article is protected by copyright. All rights reserved.

Objectives This study aimed to assess the comparative efficacy of 4 ablation strategies on the incidence rates of freedom from atrial fibrillation (AF) or atrial tachycardia (AT) through a 3-year follow-up in patients with persistent AF. Background The optimal substrate modification strategies using catheter ablation for patients with persistent AF remain unclear. Methods Patients with persistent AF were enrolled consecutively to undergo each of 4 ablation strategies: (a) Group 1 (Gp 1, n=69), pulmonary vein isolation (PVI) plus rotor ablation assisted by similarity index and phase mapping; (b) Gp 2 (n=75), PVI plus linear ablations at the left atrium; (c) Gp 3 (n=42), PVI plus elimination of complex fractionated atrial electrograms; (d) Gp 4 (n=67), PVI only. Potential confounders were adjusted via a multivariate survival parametric model. Results Baseline characteristics were similar across the 4 groups. At a follow-up period of 34.9±38.6 months, patients in Gp 1 showed the highest rate of freedom from AF compared with the other 3 groups (p=0.002), while patients in Gp 3 and 4 showed lower rates of freedom from AT than those of the other two groups (p=0.006). Independent predictors of recurrence of AF were the ablation strategy (p=0.002) and left atrial diameter (LAD) (p=0.01). Conclusion In patients with persistent AF, a substrate modification strategy using rotor ablation assisted by similarity index and phase mapping provided a benefit for maintaining sinus rhythm compared to the other strategies. Both ablation strategy and baseline LAD predicted the 3-year outcomes of freedom from AT/AF This article is protected by copyright. All rights reserved.

Black women with uterine cancer on average have worse survival outcomes compared to White women, in part due to higher rates of aggressive, non-endometrioid subtypes. However, analyses of incidence trends by specific high-risk subtypes are lacking, including those with hysterectomy and active pregnancy correction. The objective of our study was to evaluate racial disparities in age-adjusted incidence of non-endometrioid uterine cancer in 720,984 patients.Data were obtained from United States Cancer Statistics using SEER*Stat. We used the Behavioral Risk Factor Surveillance System to correct for hysterectomy and active pregnancy. Age-adjusted, corrected incidence of uterine cancer from 2001 to 2016 and annual percent change (APC) were calculated using Joinpoint regression.Of 720,984 patients, 560,131 (77.7%) were White, 72,328 (10.0%) were Black, 56,239 (7.8%) were Hispanic, and 22,963 (3.2%) were Asian/Pacific Islander. Age-adjusted incidence of uterine cancer increased from 40.8 (per 100,000) in 2001 to 42.9 in 2016 (APC = 0.5, p 0.001). Black women had the highest overall incidence at 49.5 (APC = 2.3, p 0.001). The incidence of non-endometrioid subtypes was higher in Black compared to White women, with the most pronounced differences seen in serous carcinoma (9.1 vs. 3.0), carcinosarcoma (6.1 vs. 1.8), and leiomyosarcoma (1.3 vs. 0.6). In particular, Black women aged 70-74 with serous carcinoma had the highest incidence (61.3) and the highest APC (7.3, p 0.001).Black women have a two to four-fold higher incidence of high-risk uterine cancer subtypes, particularly serous carcinoma, carcinosarcoma, and leiomyosarcoma, compared to White women after correcting for hysterectomy and active pregnancy.

Background: With respect to total mortality and cardiovascular mortality, the feature and impact of guideline-directed medication (GDM) prescriptions for heart failure with reduced ejection fraction (HFrEF) with chronic kidney disease (CKD) are unknown. Therefore, we aimed to determine these aspects. Methods: GDM prescriptions and their impact on discharged patients with and without CKD were analyzed. To analyze differences in one-year clinical outcomes, propensity score matching was conducted on a cohort of patients with concomitant HFrEF and CKD who received more and fewer GDM prescriptions. Results: A total of 1509 patients were enrolled in Taiwan's HFrEF registry from May 2013 to October 2014, and 1275 discharged patients with complete one-year follow-up were further analyzed. Of these patients, 468 (36.7%) had moderate CKD, whereas 249 (19.5%) had advanced CKD. Patients with advanced CKD received fewer prescribed GDMs than other patients. Multivariate analysis revealed that peripheral arterial occlusive disease, thyroid disorder, advanced HF at discharge, diastolic blood pressure, digoxin use, and fewer prescribed GDMs were independent predictors of one-year total mortality. After propensity score matching, patients with fewer prescribed GDMs had higher one-year total mortality rate than those with more prescribed GDMs (P=0.036). Conclusions: CKD at discharge from HF hospitalization was associated with fewer GDM prescriptions, particularly in patients with more advanced CKD. The propensity-matched analysis indicated that more GDM prescriptions led to better clinical outcomes in HFrEF patients with CKD. Careful interpretation of changes in renal function during HF hospitalization may improve GDM prescriptions.

Introduction A drug provocation test (DPT) is important for the diagnosis of Brugada syndrome (BrS). The link, however, between dynamic changes of ECG features after DPT and unstable ventricular arrhythmia (VA) in BrS remains unknown. Methods Between 2014 and 2019, we assessed 27 patients with BrS (median age: 37.0 [interquartile range, IQR: 22.0-51.0] years; 25 men], including 9 (33.3%) with a history of unstable VA and 18 (66.7%) without. All patients in the study presented with Brugada-like ECG features before DPT. The ECG parameters and dynamic changes (∆) in 12-lead ECGs recorded from the 2nd , 3rd , and 4th intercostal spaces (ICS) before and at 1, 6, 12, 18, 24 hours after DPT (oral flecainide 400 mg) were analyzed. Results The total amplitude of V1 at the 3rd ICS 18 and 24 hours after DPT was significantly lower in patients with history of unstable VA than in those without. Patients with BrS and unstable VAs had a significantly larger ∆ amplitude of V1 at the 2nd ICS 12 hours after DPT than in those without unstable VAs (0.28[0.18-0.41] mV vs. 0.08[0.01-0.15] mV, p=0.01). A multivariate analysis revealed that the amplitude of V1 at the 3rd ICS 18 and 24 hours after DPT and the ∆ amplitude of V1 at the 2nd ICS 12 hours after DPT were associated with history of unstable VA. Conclusion Nonuniform changes and spatiotemporal differences in precordial ECG features after DPT were observed in patients with BrS and these may be surrogate markers for risk stratification. This article is protected by copyright. All rights reserved.

Secretory granules (SGs) are organelles responsible for regulated exocytosis of biologically active molecules in professional secretory cells. Maturation of SGs is a crucial process in which cargoes of SGs are processed and activated, allowing them to exert their function upon secretion. Nonetheless, the intracellular trafficking pathways required for SG maturation are not well defined. We recently performed an RNA interference (RNAi) screen in Drosophila larval salivary glands to identify trafficking components needed for SG maturation. From the screen, we identified several Rab GTPases (Rabs) that affect SG maturation. Expression of constitutively active (CA) and dominant-negative (DN) forms narrowed down the Rabs important for this process to Rab5, Rab9 and Rab11. However, none of these Rabs localizes to the limiting membrane of SGs. In contrast, examination of endogenously YFP-tagged Rabs (YRabs) in larval salivary glands revealed that YRab1 and YRab6 localize to the limiting membrane of immature SGs (iSGs) and SGs. These findings provide new insights into how Rab GTPases contribute to the process of SG maturation.

To determine the long-term potential benefit of adjuvant chemotherapy in subgroups of high-risk stage I mucinous ovarian cancer patients using a predictive scoring algorithm.Data were collected from the National Cancer Database from 2004 to 2014. Based on demographic and surgical characteristics, a novel 10-year survival prognostic scoring system was developed using Cox regression.There were 2041 eligible patients with stage I mucinous ovarian cancer including 1362 (67%) with stage IA/IB disease, 598 (29%) with stage IC disease, and 81 (4%) with stage I disease not otherwise specified. Median age was 52 with a range of 13-90 years old. 737 (36%) patients were treated with adjuvant chemotherapy. Adjuvant chemotherapy was more common in patients with stage IC relative to stage IA/IB disease (69% vs. 21%, P 0.001) or with poorly-differentiated relative to well-differentiated tumors (69% vs. 23%, P 0.001). Unadjusted 10-year survival was 81% relative to 79% for patients treated with vs. without chemotherapy, respectively (P = 0.46). Patients were predicted to exhibit a low- or a high-risk of death using a multivariate Cox regression model with age, stage, grade, lymphovascular space invasion and ascites. Risk of death without vs. with adjuvant chemotherapy was similar in low-risk patients (88% vs. 84%; HR = 0.80, 95%CI = 0.56-1.15, P = 0.23) and worse in high-risk patients (51% vs. 74%; HR = 1.58, 95%CI: 1.05-2.38, P = 0.03) with stage I mucinous ovarian cancer.A predictive scoring algorithm may provide prognostic information on long-term survival and identify high-risk stage I mucinous ovarian cancer patients who might achieve a survival benefit from adjuvant chemotherapy.

ObjectiveTo evaluate the influence of marital status and other demographic factors on survival of patients with ovarian cancer.Study designData were obtained from the Surveillance, Epidemiology, and End Results database from 2010 to 2015. Analyses were performed using Kaplan–Meier and multivariate Cox proportional hazard methods.ResultsOf 19 643 patients with ovarian cancer (median age 60 years, range 18–99), 16 278 (83%), 1381 (7%), 1856 (9%), and 128 (1%) were White, Black, Asian, and Native American, respectively. The majority of patients (10 769, 55%) were married while 4155 (21%) were single, 2278 (12%) were divorced, and 2441 (12%) were widowed. Patients were more likely to be married if they were Asian (65%) or White (56%) than if they were Black (31%) or Native American (39%) (pConclusionMarried patients with ovarian cancer were more likely to undergo chemotherapy with better survival rates. Black, uninsured, or patients with Medicaid insurance had poorer outcomes.

Excitation-contraction coupling from the integration of action potential duration (APD) and muscle contractility plays an important role in arrhythmogenesis. We aimed to determine whether distinctive excitation-contraction coupling contributes to the genesis of ventricular tachycardias (VTs). Action potential (AP) and mechanical activity were simultaneously recorded under electrical pacing (cycle lengths from 1000 to 100 ms) in the tissue model created from isolated rabbit right ventricular outflow tracts treated with NS 5806 (10 μM, transient outward potassium current enhancer), pinacidil (2 μM, ATP-sensitive potassium channel opener), and pilsicainide (5 μM, sodium channel blocker). There were 15 (9.9%) inducible VT episodes (group 1) and 136 (90.1%) non-inducible VT episodes (group 2) in our tissue model. Group 1 had greater post-pacing increases of the first occurrence of AP at 90% repolarization (ΔAPD90, p 15% and a ΔContractility > 270%, but were undetectable in those with a ΔAPD90 < 15% and a ΔContractility < 270%. In those with pacing-induced VTs, KB-R7943 (10 μM, a Na+-Ca2+ exchanger inhibitor, NCX inhibitor) significantly reduced the occurrence of VTs from 100.0 to 20.0% (15/15 to 3/15 episodes, p < 0.001). Concurrent increases in both post-pacing APD and contractility resulted in the occurrence of ventricular arrhythmias. NCX inhibition may be a potential therapeutic strategy for ventricular arrhythmias.

IntroductionA recent randomized clinical trial showed that minimally invasive surgery led to poorer survival compared with open surgery in early stage cervical cancer. We determined the trends in adoption of minimally invasive surgery and 5-year overall survival outcomes after open, laparoscopic-assisted, and robotic-assisted hysterectomy for stage II uterine cancer with cervical stromal involvement.MethodsData for patients with stage II uterine cancer were acquired from the National Cancer Database from 2010 to 2015. χ2testing, Kaplan–Meier methods, and Cox models were used for statistical analyses.ResultsOf 2949 patients, 44.3% underwent open hysterectomy, 13.9% underwent laparoscopic hysterectomy, and 41.8% underwent robotic hysterectomy. The proportion of robotic cases increased from 26.8% in 2010 to 48.3% in 2015 (annual percent change 10.1%), with a decrease in open hysterectomy from 63.3% to 34.3% (annual percent change –12.5%). The overall 5-year survival was 77.6% in robotic, 76.8% in laparoscopic, and 72.5% in open hysterectomy (p=0.045); however, after adjusting for known prognostic factors, robotic (HR 1.00, 95% CI 0.82 to 1.21; p=0.97) and laparoscopic hysterectomy (HR 1.09, 95% CI 0.83 to 1.44; p=0.54) did not portend for improved survival compared with open hysterectomy. Black women (HR 1.59, 95% CI 1.25 to 2.02; pConclusionThe use of minimally invasive surgery for stage II uterine cancer has increased over time, with comparable adjusted 5-year survival after robotic or laparoscopic hysterectomy compared with open hysterectomy. Black women and those with co-morbidities had lowest rates of minimally invasive surgery and the poorest adjusted survival.

Background Many Asian patients desire a narrower nasal base with less flaring of the alar lobules. However, patients who underwent multiple rhinoplasty surgeries with nostril contracture or an overreduction of the alar base may experience nostril contracture and deformity, which may lead to further airway obstruction. We present a technique that combines paranasal augmentation with composite chondrocutaneous graft transfer to overcome this problem. Methods Nine patients underwent composite chondrocutaneous graft transfer to the soft triangle or alar base combined with paranasal augmentation using preshaped porous polyethylene implants to correct nostril contracture and airway obstruction between September of 2014 and May of 2018. Preoperative and postoperative alar base distances and cross-sectional areas of the nostrils were measured and compared. Results The average thickness of paranasal augmentation was 5.5 mm (range, 4.0-7.0 mm). Eighteen composite grafts were located over the soft triangle (n = 3) and the alar base (n = 15). The average number of composite grafts for each person was 2 (range, 1-4). All composite grafts survived totally or partially, and no graft failed. The average follow-up was 10.9 months (range, 3-28 months). The alar base increased 13.9% (range, 2.2%-23.9%), and the nostril area increased an average of 78.1% (range, 4.5%-316.8%) postoperatively. Patients had satisfactory aesthetic and functional outcomes. Conclusions Combining paranasal augmentation and composite graft transfer increased the cross-sectional area of the external valve and improved nostril contracture and airway obstruction after the overresection of the alar base or nose contracture after multiple rhinoplasty surgeries.

INTRODUCTION Accurate identification of slow conducting regions in patients with scar-related atrial tachycardia (AT) is difficult using conventional electrogram annotation for cardiac electroanatomic mapping (EAM). Estimating delays between neighboring mapping sites is a potential option for activation map computation. We describe our initial experience with CARTO 3 Coherent Mapping (Biosense Webster Inc,) in the ablation of complex ATs. METHODS Twenty patients (58 ± 10 y/o, 15 males) with complex ATs were included. We created three-dimensional EAMs using CARTO 3 system with CONFIDENSE and a high-resolution mapping catheter (Biosense Webster Inc). Local activation time and coherent maps were used to aid in the identification of conduction isthmus (CI) and focal origin sites. System-defined slow or nonconducting zones and CI, defined by concealed entrainment (postpacing interval

Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker.We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671-13,879; N controls = 173,493-372,016), FinnGen (N cases = 719-8401; N controls = 74,685-174,006) and several international cancer genetic consortia (N cases = 11,348-122,977; N controls = 15,861-105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach.Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95% CI 1.04-1.20, p = 0.002). The direction of the genetically predicted effects was consistent across main and sensitivity MR analyses. Among subtypes, the genetically predicted effect of GrimAge acceleration was greater for colon cancer (IVW OR = 1.15, 95% CI 1.09-1.21, p = 0.006), than rectal cancer (IVW OR = 1.05, 95% CI 0.97-1.13, p = 0.24). Results were less consistent for associations between other epigenetic clocks and cancers.GrimAge acceleration may increase the risk of colorectal cancer. Findings for other clocks and cancers were inconsistent. Further work is required to investigate the potential mechanisms underlying the results.FMB was supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (224982/Z/22/Z which is part of grant 218495/Z/19/Z). KKT was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) and by the Hellenic Republic's Operational Programme 'Competitiveness, EntrepreneurshipInnovation' (OΠΣ 5047228). PH was supported by Cancer Research UK (C18281/A29019). RMM was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. GDS and CLR were supported by the Medical Research Council (MC_UU_00011/1 and MC_UU_00011/5, respectively) and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). REM was supported by an Alzheimer's Society project grant (AS-PG-19b-010) and NIH grant (U01 AG-18-018, PI: Steve Horvath). RCR is a de Pass Vice Chancellor's Research Fellow at the University of Bristol.Have you noticed that some people seem to get older faster than others? Scientists have previously found that a chemical tag on DNA known as DNA methylation can be used to predict an individual’s chronological age. However, age predicted using DNA methylation (also known as biological or epigenetic age) does not always perfectly correspond to chronological age. Indeed, some people’s biological age is higher than their years, while other people’s is lower. When an individual’s biological age is higher than their chronological age, they are said to be experiencing ‘epigenetic age acceleration’. This type of accelerated ageing, which can be measured with ‘epigenetic clocks’ based on DNA methylation, has been associated with several adverse health outcomes, including cancer. This means that epigenetic clocks may improve our ability to predict cancer risk and detect cancer early. However, it is still unclear whether accelerated biological ageing causes cancer, or whether it simply correlates with the disease. Morales-Berstein et al. wanted to investigate whether epigenetic age acceleration, as measured by epigenetic clocks, plays a role in the development of several cancers. To do so, they used an approach known as Mendelian randomization. Using genetic variants as natural experiments, they studied the effect of different measures of epigenetic age acceleration on cancer risk. Their work focused on five types of cancer: breast, colorectal, prostate, ovarian and lung cancer. They used genetic association data from people of European ancestry to determine whether genetic variants that are strongly associated with accelerated ageing are also strongly associated with cancer. The results showed that one of the DNA methylation markers used as an estimate of biological ageing could be directly related to the risk of developing colorectal cancer. This work provides new insights into the relationship between markers of biological ageing and cancer. Similar relationships should also be studied in other groups of people and for other cancer sites. The results suggest that reversing biological ageing by altering DNA methylation could prevent or delay the development of colorectal cancer.

A second generation and scaled-up equipment, named Aligo-2TM (microwave-assisted induction heating, MAIH) with a sample capacity of approximately 1.0 L was designed and invented by Bottle Top Machinery Co., Ltd., Taiwan. Pre-packaged raw shrimps were heated in a scaled-up system using heating temperatures of 130 °C and 90 °C for 80 to 150 s, and the physicochemical and microbial qualities were evaluated. The total plate count, psychrotrophic bacteria count, and coliform levels decreased as heating time increased, whereas the cooking loss, color (L*, a*, and W) value, and texture increased. When shrimps were heated for the longest time of 120 s at 130 °C or 150 s at 90 °C, they displayed obvious overcooked, shrunken, and dry appearance. To obtain samples that showed a red color, cooked well, and had no microbial count, better heating conditions for the processing of pre-packaged shrimps via the MAIH scale-up system were 130 °C for 100 s or 90 °C for 130 s. This novel and scaled-up MAIH equipment provides shrimp to be cooked after being packed, thereof avoiding the post-contamination problem.

Symmetry and balance in nasal reconstruction can be hard to achieve. Traditionally, a foil template modeled after the unaffected contralateral side is used in the design of a forehead flap. Crude two-dimensional models often generate underwhelming results. To better simulate complex nasal topography, three-dimensional printing technology was applied to nasal reconstruction.Between May 2012 and October 2016, twenty patients underwent forehead flap nasal reconstruction for heminasal deformities. Ten reconstructions were guided with prefabricated three-dimensional templates (CAD/CAM), and ten patients underwent traditional nasal reconstruction without CAD/CAM. In the CAD/CAM group, two templates were printed: contour guide and framework guide. These were a reference for skin flap design and cartilage framework design, respectively. Photographic records and photogrammetry was used to evaluate results.The mean follow-up time was 19.3 months (range, 6 months to 38 months) in the control group and 17.4 months (range, 7 months to 35 months) in the CAD/CAM group. Without CAD/CAM, there was asymmetry in alar width, alar area, nostril height, width and area (p0.05) between reconstructed and native structures. In the CAD/CAM group, there were asymmetries of nostril-related parameters only. After quantifying asymmetries as a percentage, the CAD/CAM group demonstrated more symmetric reconstructions, particularly in alar width (p = 0.043) and alar area (p = 0.003).When CAD/CAM guidance and three-dimensional printing was used, there was greater symmetry between reconstructed and native structures of the nose.

Introduction We aimed to clarify the effect of vein of Marshall (VOM) ethanol infusion for treating VOM triggers and/or mitral flutter after first-attempt endocardial ablation in patients with nonparoxysmal atrial fibrillation (AF). Methods and results Of the 254 consecutive patients (age, 56 ± 10 years; 221 male) undergoing catheter ablation for drug-refractory nonparoxysmal AF, 32 (12.6%) received VOM ethanol infusion. The patients were stratified into group 1 (pulmonary vein isolation [PVI], substrate modification, VOM ethanol infusion), group 2 (PVI, substrate modification), and group 3 (PVI alone). Propensity-matched analysis (N = 128) of long-term outcomes (3.9 ± 0.5 years) revealed a higher AF recurrence risk in group 2 (hazard ratio [HR], 4.17; 95% confidence interval [95% CI], 1.63-10.69; P = .003) and group 3 (HR, 1.82; 95% CI, 1.09-3.04; P = .021) than in group 1, as well as a higher atrial arrhythmia recurrence risk in group 2 than in group 1 (HR, 2.42; 95% CI, 1.16-5.03; P = .018). A higher procedural termination rate was observed in group 1 than groups 2 and 3 (41.7% vs 17.2% vs 18.8%; P = .042). On multivariate analysis, VOM ethanol injection was an independent predictor of freedom from recurrence of AF (HR, 0.20; 95% CI, 0.08-0.52; P = .001) and atrial arrhythmia (HR, 0.35; 95% CI, 0.17-0.74; P = .005), whereas a left atrial diameter >45 mm and hypertension were independent risk factors for recurrence. Periprocedural complications rates were comparable among the groups. Conclusion Adjunctive VOM ethanol infusion is effective and safe for treating nonparoxysmal AF in patients with VOM triggers and/or refractory mitral flutter, providing good long-term freedom from AF and atrial arrhythmia.

Airway collapse can occur when the forces of inhalation overpower the strength of the nasal lining flap. The authors established an animal model of the reconstructed nasal airway, and examined mechanical properties of tissue composites based on various materials. Twenty-three Sprague-Dawley rats were divided into three experimental groups: control (n = 5), irradiated homologous costal cartilage (IHCC, n = 10), and expanded polytetrafluoroethylene (ePTFE, n = 8). Two dorsal skin flaps represented nasal lining and skin envelope. No framework, an IHCC or ePTFE rim graft was used as framework. At three weeks, changes in the cross-sectional area of the lining flap were measured when negative pressure was applied. En-bloc specimens containing the graft and soft tissue were examined for histological change and tissue ingrowth. Reduction of cross-sectional area with simulated inhalation was 87.74% in the control group, 82.76% (IHCC), and 67.29% (ePTFE). Cross-sectional reduction was significantly less in ePTFE group than control group (p = 0.004) and IHCC group (p = 0.001). The difference was not significant in the control and IHCC groups. There was histologic evidence of tissue ingrowth in the ePTFE group. This novel animal model of nasal airway reconstruction supports the use and potential benefit of using ePTFE for prevention of airway collapse.

Whether bleeding should be considered a sufficient sign to justify thorough cancer surveillance in atrial fibrillation (AF) patients receiving nonvitamin K antagonist oral anticoagulants (NOACs) remains unclear. We investigated the relationships between bleeding events and new-onset cancers in AF patients receiving NOACs in a prospective cohort (n = 395, mean follow-up duration of 2.8 years). There were 18 patients who were diagnosed with new-onset cancers 584 ± 372 days after the initiation of NOACs. The patients with new-onset cancers had higher HAS-BLED scores (no, preexisting and new-onset cancer: 1.51 ± 0.81, 1.69 ± 0.87, and 2.11 ± 0.96, respectively; p = 0.006) and a higher incidence of bleeding events (22%, 33%, 67%, respectively; p0.001) than did patients without new-onset cancers. Bleeding events that preceded the diagnosis of new-onset cancers were independently correlated with new-onset cancers (odds ratio: 7.89, p = 0.001) in the multivariate logistic regression. More than half of the patients (61%) with new-onset cancers had either a significant period of drug interruption for at least 2 months or discontinued NOACs. In conclusions, bleeding in AF patients receiving NOACs could be an alerting sign of new-onset cancers and should prompt the initiation of thorough surveillance to detect early cancers.

Background Transmural lesion creation is essential for effective atrial fibrillation (AF) ablation. Lesion characteristics between conventional energy and high-power short-duration (HPSD) setting in contact force-guided (CF) ablation for AF remained unclear. Methods Eighty consecutive AF patients who received CF with conventional energy setting (power control: 25–30 W, force–time integral = 400 g s, n = 40) or with HPSD (power control: 40–50 W, 10 s, n = 40) ablation were analyzed. Of them, 15 patients in each conventional and HPSD group were matched by age and gender respectively for ablation lesions analysis. Type A and B lesions were defined as a lesion with and without significant voltage reduction after ablation, respectively. The anatomical distribution of these lesions and ablation outcomes among the 2 groups were analyzed. Results 1615 and 1724 ablation lesions were analyzed in the conventional and HPSD groups, respectively. HPSD group had a higher proportion of type A lesion compared to conventional group (P P = 0.04). The procedure time and ablation time were significantly shorter in the HPSD group than that in the conventional group (91.0 ± 12.1 vs. 124 ± 14.2 min, P = 0.03; 30.7 ± 19.2 vs. 57.8 ± 21 min, P = 0.02, respectively). At a mean follow-up period of 11 ± 1.4 months, there were 13 and 7 patients with recurrence in conventional and HPSD group respectively (P = 0.03). Conclusion Optimal ablation lesion characteristics and distribution after conventional and HPSD ablation differed significantly. HPSD ablation had shorter ablation time and lower recurrence rate than did conventional ablation.

The prognostic value of genetic variants for predicting lethal arrhythmic events (LAEs) in Brugada syndrome (BrS) remains controversial. We investigated whether the functional curation of SCN5A variations improves prognostic predictability.Using a heterologous expression system and whole-cell patch clamping, we functionally characterized 22 variants of unknown significance (VUSs) among 55 SCN5A mutations previously curated using in silico prediction algorithms in the Japanese BrS registry (n = 415). According to the loss-of-function (LOF) properties, SCN5A mutation carriers (n = 60) were divided into two groups: LOF-SCN5A mutations and non-LOF SCN5A variations. Functionally proven LOF-SCN5A mutation carriers (n = 45) showed significantly severer electrocardiographic conduction abnormalities and worse prognosis associated with earlier manifestations of LAEs (7.9%/year) than in silico algorithm-predicted SCN5A carriers (5.1%/year) or all BrS probands (2.5%/year). Notably, non-LOF SCN5A variation carriers (n = 15) exhibited no LAEs during the follow-up period. Multivariate analysis demonstrated that only LOF-SCN5A mutations and a history of aborted cardiac arrest were significant predictors of LAEs. Gene-based association studies using whole-exome sequencing data on another independent SCN5A mutation-negative BrS cohort (n = 288) showed no significant enrichment of rare variants in 16 985 genes including 22 non-SCN5A BrS-associated genes as compared with controls (n = 372). Furthermore, rare variations of non-SCN5A BrS-associated genes did not affect LAE-free survival curves.In vitro functional validation is key to classifying the pathogenicity of SCN5A VUSs and for risk stratification of genetic predictors of LAEs. Functionally proven LOF-SCN5A mutations are genetic burdens of sudden death in BrS, but evidence for other BrS-associated genes is elusive.

Background: Surgical scars cause an intra-atrial conduction delay and anatomical obstacles that facilitate the perpetuation of atrial flutter (AFL). This study aimed to investigate the outcome and predictor of recurrent atrial tachyarrhythmia after catheter ablation in patients with prior cardiac surgery for valvular heart disease (VHD) who presented with AFL.Methods: Seventy-two patients with prior cardiac surgery for VHD who underwent AFL ablation were included. The patients were categorized into a typical AFL group (n = 45) and an atypical AFL group (n = 27). The endpoint was the recurrence of atrial tachyarrhythmia during follow-up. A multivariate analysis was performed to determine the predictor of recurrence.Results: No significant difference was found in the recurrence rate of atrial tachyarrhythmia between the two groups. Patients with concomitant atrial fibrillation (AF) had a higher recurrence of typical AFL compared with those without AF (13 vs. 0%, P = 0.012). In subgroup analysis, typical AFL patients with concomitant AF had a higher incidence of recurrent atrial tachyarrhythmia than those without it (53 vs. 14%, P = 0.006). Regarding patients without AF, the typical AFL group had a lower recurrence rate of atrial tachyarrhythmia than the atypical AFL group (14 vs. 40%, P = 0.043). Multivariate analysis showed that chronic kidney disease (CKD) and left atrial diameter (LAD) were independent predictors of recurrence.Conclusions: In our study cohort, concomitant AF was associated with recurrence of atrial tachyarrhythmia. CKD and LAD independently predicted recurrence after AFL ablation in patients who have undergone cardiac surgery for VHD.

Whether deep sedation with intravenous anesthesia will affect the recurrence after cryoballoon ablation (CBA) of paroxysmal atrial fibrillation (AF) is yet to be examined. Thus, in this study, we hypothesize that there is difference in terms of the recurrence between local anesthesia and deep sedation with intravenous anesthesia after an index ablation procedure.In total, 109 patients were enrolled and received CBA, of which 68 (58.2 years) patients underwent pulmonary vein (PV) isolation with a local anesthesia (group 1) and 41 patients (63.2 years) underwent PV isolation with deep sedation using intravenous anesthesia (group 2).During the index procedure, isolation of all major PVs was achieved in 66 patients in group 1 and in 41 patients in group 2. There was no difference in non-PV triggers between the two groups. The periprocedural complication was found to be similar between the two groups (2.9% in group 1 and 4.9% in group 2). Further, 17 patients in group 1 and 4 patients in group 2 experienced recurrences after a follow-up of 19.3 months (P = 0.019). Repeat procedures revealed similar PV reconnection rates between the two groups. It has also been noted that the number of reconnected PV and incidence of atypical flutter seem to increase in group 1.Deep sedation with intravenous anesthesia during CBA for paroxysmal AF is safe and had a better long-term outcome than those with local anesthesia.

The predictive value of non-invasive electrocardiographic examination findings for the risk of sudden cardiac death (SCD) in populations with structurally normal hearts remains unclear. This study aimed to investigate the characteristics of the QRS vectorcardiography of surface electrocardiography in patients with structurally normal hearts who experienced SCD. We consecutively enrolled patients who underwent vectorcardiography between March 2017 and December 2018 in a tertiary referral medical center. These patients didn’t have structural heart diseases, histories of congestive heart failure, or reduced ejection fraction, and they were classified into SCD (with aborted SCD history and cerebral performance category score of 1) and control groups (with an intervention for atrioventricular node reentrant tachycardia and without SCD history). A total of 162 patients (mean age, 54.3±18.1 years; men, 75.9%), including 59 in the SCD group and 103 in the control group, underwent propensity analysis. The baseline demographic variables, underlying diseases, QRS loop descriptors (the percentage of the loop area, loop dispersion, and inter-lead QRS dispersion), and other electrocardiographic parameters were compared between the two groups. In the univariate and multivariate analyses, a smaller percentage of the loop area (odds ratio, 0.0003; 95% confidence interval, 0.00–0.02; p4-5 dispersion (odds ratio, 1.04; 95% confidence interval, 1.02–1.07; p = 0.002), and longer QRS duration (odds ratio, 1.05; 95% confidence interval, 1.00–1.10; p = 0.04) were associated with SCD. In conclusion, the QRS loop descriptors of surface electrocardiography could be used as non-invasive markers to identify patients experiencing aborted SCD from a healthy population. A decreased percentage of loop area and elevated V4-5 QRS dispersion values assessed using vectorcardiography were associated with an increased risk of SCD in patients with structurally normal hearts.

The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS‐CoV‐2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS‐CoV‐2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro‐inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro‐inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus‐specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS‐CoV‐2 was observed in asymptomatic patients. In addition, asymptomatic COVID‐19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro‐inflammatory and more protective immune responses against SARS‐CoV‐2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID‐19., We show that asymptomatic patients elicit a different repertoire of immune responses from symptomatic patients. Our data suggest that asymptomatic patients could limit symptom development with a well‐balanced inflammatory response and more protective immune responses against SARS‐CoV‐2.

Introduction: Lung cancer survivors are at high risk of developing a second primary lung cancer (SPLC). However, SPLC risk factors have not been established and the impact of tobacco smoking remains controversial. We examined the risk factors for SPLC across multiple epidemiologic cohorts and evaluated the impact of smoking cessation on reducing SPLC risk.Methods: We analyzed data from 7059 participants in the Multiethnic Cohort (MEC) diagnosed with an initial primary lung cancer (IPLC) between 1993 and 2017. Cause-specific proportional hazards models estimated SPLC risk. We conducted validation studies using the Prostate, Lung,Colorectal, and Ovarian Cancer Screening Trial (N = 3423 IPLC cases) and European Prospective Investigation into Cancer and Nutrition (N = 4731 IPLC cases) cohorts and pooled the SPLC risk estimates using random effects meta analysis.Results: Overall, 163 MEC cases (2.3%) developed SPLC. Smoking pack-years (hazard ratio [HR] = 1.18 per 10 pack years, p < 0.001) and smoking intensity (HR = 1.30 per 10 cigarettes per day, p < 0.001) were significantly associated with increased SPLC risk. Individuals who met the 2013 U.S. Preventive Services Task Force's screening criteria at IPLC diagnosis also had an increased SPLC risk (HR = 1.92; p < 0.001). Validation studies with the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and European Prospective Investigation into Cancer and Nutrition revealed consistent results. Meta-analysis yielded pooled HRs of 1.16 per 10 pack-years (p(meta) < 0.001), 1.25 per 10 cigarettes per day (p(meta) < 0.001), and 1.99 (p(meta) < 0.001) for meeting the U.S. Preventive Services Task Force's criteria. In MEC, smoking cessation after IPLC diagnosis was associated with an 83% reduction in SPLC risk (HR = 0.17; p < 0.001).Conclusions: Tobacco smoking is a risk factor for SPLC. Smoking cessation may reduce the risk of SPLC. Additional strategies for SPLC surveillance and screening are warranted. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Aims: The current study aims to verify the feasibility and safety of chronic total occlusion (CTO)-percutaneous coronary intervention (PCI) via the distal transradial access (dTRA).Methods: Between April 2017 and December 2019, 298 patients who underwent CTO PCI via dTRA were enrolled in this study. The baseline demographic and procedural characteristics were listed and compared between groups. The incidences of access-site vascular complications and procedural complications and mortality were recorded.Results: The mean J-CTO (Japanese chronic total occlusion) score was 2.6 ± 0.9 points. The mean access time was 4.6 ± 2.9 min, and the mean procedure time was 115.9 ± 55.6 min. Left radial snuffbox access was performed successfully in 286 patients (96.5%), and right radial snuffbox access was performed successfully in 133 patients (97.7%). Bilateral radial snuffbox access was performed in 107 patients (35.9%). 400 dTRA (95.5%) received glidesheath for CTO intervention. Two patients (0.7%) developed severe access-site vascular complications. None of the patients experienced severe radial artery spasm and only 2 patients (0.5%) developed radial artery occlusion during the follow-up period. The overall procedural success rate was 93.5%. The procedural success rate was 96.5% in patients with antegrade approach and 87.7% in patients with retrograde approach.Conclusions: It is both safe and feasible to use dTRA plus Glidesheath for complex CTO intervention. The incidences of procedure-related complications and severe access-site vascular complications, and distal radial artery occlusion were low.

Environmental contamination by microplastics (MPs) is an emerging concern in recent years due to associated adverse impacts of MPs on potential human health problems. Endothelial dysfunction is a condition in which the endothelial layer fails to form normally, and is associated with impaired vascular function. Despite the fact that MPs are known to enter the circulation system through intestinal epithelium, little has been known whether MPs impact the normal function of endothelial cells and the formation of vasculature. In the current study, we investigated the effect of polystyrene microplastics (PS-MPs) on tube formation and cytotoxicity in human umbilical vein endothelial cells (HUVECs). Our study showed that the treatment of HUVECs with PS-MPs significantly decreased cell viability, with intracellular accumulation occurring in a dose- and size-dependent manner. Moreover, significant dose-dependent inhibition of angiogenic tube formation was observed in HUVECs treated with 0.5 μm PS-MPs; this effect was accompanied by suppression of angiogenic signaling pathways and inhibitory activity against wound healing and cell migration. Regarding the mechanism of decreased viability, we observed increased autophagic and necrotic cell death. These results indicate that 6-h exposure of endothelial cells to PS-MPs represses tube-forming capacity, while 48-h exposure leads to autophagy and necrosis-mediated cytotoxicity.

INTRODUCTION Identifying the critical isthmus (CI) in scar-related macroreentrant atrial tachycardia (AT) is challenging, especially for patients with cardiac surgery. We aimed to investigate the electrophysiological characteristics of scar-related macroreentrant ATs in patients with and without cardiac surgery. METHODS A prospective study of 31 patients (mean age 59.4 ± 9.81 years old) with scar-related macroreentrant ATs were enrolled for investigation of substrate properties. Patients were categorized into the nonsurgery (n = 18) and surgery group (n = 13). The CIs were defined by concealed entrainment, conduction velocity less than 0.3 m/s, and the presence of local fractionated electrograms. RESULTS Among the 31 patients, a total of 65 reentrant circuits and 76 CIs were identified on the coherent map. The scar in the surgical group is larger than the nonsurgical group (18.81 ± 9.22 vs. 10.23 ± 5.34%, p = .016). The CIs in surgical group have longer CI length (15.27 ± 4.89 vs. 11.20 ± 2.96 mm, p = .004), slower conduction velocity (0.46 ± 0.19 vs. 0.69 ± 0.14 m/s, p

Background Augmentation rhinoplasty had become increasingly popular among Asians. Failure to recognize nasal deviation before surgery may engender unsatisfactory outcomes because the deviation becomes prominently visible after surgery due to the central position of the nose. Ideal nasal radix positioning has yet to be addressed. The head position affects facial asymmetry judgements; however, its effect on rhinoplasty has never been studied. This study determined the ideal nasal radix position in facial fluctuating asymmetry and investigated the effects of the natural head position (NHP) on nasal deviation perceptions. Methods A survey was conducted to compare different head and nasal radix horizontal positions using images of patients who underwent augmentation rhinoplasty. Images were retouched using editing software to adjust the head and nasal radix positions. The survey was performed using questionnaires involving 3 plastic surgeons and 3 laypersons, who were asked to determine the presence of nasal deviation and select the ideal nasal radix position among the retouched images. Results Twenty patients who underwent primary rhinoplasty were included in this study. The recognition of nasal deviation was significantly higher in the NHP than in the compensatory head position. The surgeons and the laypersons considered the midsagittal line the most appropriate position of the nasal radix. Conclusions Facial analysis for augmentation rhinoplasty should be performed with the patient's head in the NHP to prevent nasal deviation masking. The preferred nasal radix position in facial fluctuating asymmetry is the midsagittal line.Level of Evidence: Level V, descriptive study.

Vascular smooth muscle cells (SMCs) are important vascular components that are essential for the regulation of vascular functions during vascular atherosclerogenesis and vascular injury. Oxidized low-density lipoprotein (oxLDL) is known to induce SMC activation and foam cell transformation. This study characterized the role of hepatoma-derived growth factor (HDGF) in oxLDL-induced foam cell formation in cultured primary rat aortic SMCs. OxLDL exposure significantly increased HDGF expression and extracellular release. It also upregulated atherogenic regulators in SMCs, including TLR4, MyD88, LOX-1, and CD36. Exogenous HDGF stimulation not only increased the expression of cognate receptor nucleolin, but also the innate immunity regulators TLR4/MyD88 and lipid metabolism regulators, including LOX-1 and CD36. Oil red O staining showed that HDGF did not initiate, but enhanced oxLDL-driven foam cell formation in SMCs. Further signaling characterization demonstrated that oxLDL evoked activation of PI3K/Akt and p38 MAPK signaling pathways, both of which were involved in the upregulation of HDGF, LOX-1, and CD36 induced by oxLDL. Gene knockdown experiments using LOX-1 targeted siRNA demonstrated that LOX-1 expression was critical for oxLDL-induced HDGF upregulation, while HDGF gene depletion completely abolished oxLDL-triggered TLR4, LOX-1, and CD36 overexpression and foam cell formation in SMCs. These findings strongly suggest that oxLDL-induced HDGF upregulation participates in subsequent LOX-1 and CD36 expression in aortic SMCs and mechanistically contributes to the formation of SMC-derived foam cells. The oxLDL/LOX-1/HDGF axis may serve as a target for anti-atherogenesis therapy.

Early detection of infections is crucial to limit the spread of coronavirus 2019 disease (COVID-19). Here, we develop a flow cytometry-based assay to detect SARS-CoV-2 Spike protein (S protein) antibodies in COVID-19 patients. The assay detects specific IgM, IgA and IgG in COVID-19 patients and also the acquisition of all IgG subclasses, with IgG1 being the most dominant. The antibody response is significantly higher at a later stage of the infection. Furthermore, asymptomatic COVID-19 patients also develop specific IgM, IgA and IgG, with IgG1 as the most dominant subclass. Although the antibody levels are lower in asymptomatic infections, the assay is highly sensitive and detect 97% of asymptomatic infections. These findings demonstrate that the assay can be used for serological analysis of symptomatic infections, and also asymptomatic infections, which may, otherwise, go undetected., Graphical Abstract, Highlights Flow cytometry assay detects specific antibodies in symptomatic COVID-19 patients. Asymptomatic COVID-19 patients also develop specific antibodies. IgG1 is the dominant IgG subclass in both symptomatic and asymptomatic patients. The assay is highly sensitive and detects 97% of asymptomatic infections., Using a flow cytometry-based assay, Goh et al. finds specific antibodies in symptomatic COVID-19 patients’ plasma samples. IgG1 is the most dominant IgG subclass. Despite lower antibody levels, the assay detects 97% of asymptomatic infections, suggesting the feasibility of the assay to detect asymptomatic infections, which may otherwise go undetected.

Objectives The emergence of a SARS‐CoV‐2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross‐neutralise against the G614 variant. Methods Antibody profiling against the SARS‐CoV‐2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS‐CoV‐2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID‐19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). Results Profiling of the anti‐SARS‐CoV‐2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. Conclusions Cross‐reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS‐CoV‐2. More importantly, there should be negligible impact towards the efficacy of antibody‐based therapies and vaccines that are currently being developed., A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS‐CoV‐2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody‐mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine whether humoral immunity acquired from the original SARS‐CoV‐2 isolate is able to induce cross‐detection and cross‐protection against the novel prevailing D614G variant. In this study, we demonstrated an overall equivalent neutralising capacity against both the D614 and G614 pseudoviruses, suggesting negligible impact towards the efficacy of antibody‐based therapies and vaccines that are currently being developed.