The impact of lipidome on breast cancer: a Mendelian randomization study.

OBJECTIVE: This study aims to investigate the association between specific lipidomes and the risk of breast cancer (BC) using the Two-Sample Mendelian Randomization (TSMR) approach and Bayesian Model Averaging Mendelian Randomization (BMA-MR) method. METHOD: The study analyzed data from large-scale GWAS datasets of 179 lipidomes to assess the relationship between lipidomes and BC risk across different molecular subtypes. TSMR was employed to explore causal relationships, while the BMA-MR method was carried out to validate the results. The study assessed heterogeneity and horizontal pleiotropy through Cochran's Q, MR-Egger intercept tests, and MR-PRESSO. Moreover, a leave-one-out sensitivity analysis was performed to evaluate the impact of individual single nucleotide polymorphisms on the MR study. RESULTS: By examining 179 lipidome traits as exposures and BC as the outcome, the study revealed significant causal effects of glycerophospholipids, sphingolipids, and glycerolipids on BC risk. Specifically, for estrogen receptor-positive BC (ER+ BC), phosphatidylcholine (P < 0.05) and phosphatidylinositol (OR: 0.916-0.966, P < 0.05) within glycerophospholipids play significant roles, along with the importance of glycerolipids (diacylglycerol (OR = 0.923, P < 0.001) and triacylglycerol, OR: 0.894-0.960, P < 0.05)). However, the study did not observe a noteworthy impact of sphingolipids on ER+BC. In the case of estrogen receptor-negative BC (ER- BC), not only glycerophospholipids, sphingolipids (OR = 1.085, P = 0.008), and glycerolipids (OR = 0.909, P = 0.002) exerted an influence, but the protective effect of sterols (OR: 1.034-1.056, P < 0.05) was also discovered. The prominence of glycerolipids was minimal in ER-BC. Phosphatidylethanolamine (OR: 1.091-1.119, P < 0.05) was an important causal effect in ER-BC. CONCLUSIONS: The findings reveal that phosphatidylinositol and triglycerides levels decreased the risk of BC, indicating a potential protective role of these lipid molecules. Moreover, the study elucidates BC's intricate lipid metabolic pathways, highlighting diverse lipidome structural variations that may have varying effects in different molecular subtypes.

Exploring the NRF2-TP53 Signaling Network Through Machine Learning and Pan-Cancer Analysis: Identifying Potential targets for Cancer Prognosis Related to Oxidative Stress.

Oxidative stress (OXS) is closely related to tumor prognosis and immune response, while TP53 integrated with NRF2 is closely associated with the regulation of cancer-related OXS. Hence, constructing a TP53-NRF2 integrated OXS signature of pan-cancer is essential in predicting survival prognosis and facilitating cancer drug treatment. The pan-cancer analysis acquired the Cancer Genome Atlas (TCGA) transcriptome sequencing data from UCSC Xena, which consisted of 33 cancer types (n = 10 440). The Random Forest, Lasso regression, and Cox regression analyses are used to construct an OXS score based on 25 OXS genes. Following this, based on the OXS signature, patients are categorized into low- and high-risk groups. The disparities between the two cohorts regarding survival prognosis, immune infiltration, and drug sensitivity are delved deeply. The expression level of genes is confirmed using immunohistochemistry. The prognosis of pan-cancer patients is adequately predicted by the OXS signature with the assistance of the machine-learning algorithm. A highly accurate nomogram is developed by combining the OXS signature and clinical features. The presence of immune cells indicated that the OXS signature can be associated with the critical pathways of immunotherapy for all types of cancer, and BCL2 showed promising results. Distinct inter-group differences are observed in the OXS signature for frequently utilized antineoplastic medications in clinical settings, including first-line drugs suggested in the guidelines. In summary, by conducting a thorough analysis of OXS genes, a new model based on OXSscore is successfully developed. This model can predict the clinical prognosis and drug sensitivity of pan-cancer with high accuracy. Potential stars in the field of cancer-related anti-OXS may include drugs that target BCL2.

Novel Noninvasive Hybrid Flap Preconditioning (HFP) Surpasses Surgical Delay in the Murine Model.

BACKGROUND: Ischemic necrosis in the distal portion of the flap is a challenging complication in plastic surgery. We hypothesize a novel hybrid flap preconditioning (HFP) device combining foam-mediated external suction and non-surgical delay can promote skin flap survival better than surgical delay. METHOD: Twenty-eight mouse were divided into four groups. Control group: a 4*1.5 dorsal flap was made with no preconditioning. Surgical delay (SD) group: surgical delay was made 7 days before flap elevation. Foam-mediated external suction (FMES) group: foam-mediated external suction at -100mmHg was employed 5 hours per day for 6 days, and the flap was elevated on the seventh day. Hybrid Flap Preconditioning (HFP) group: silicone strips was applied along the contour of the foam interface. Same negative pressure protocol was used as the FMES group. Seven days after flap elevation, macroscopic, histologic, and Western blot analyses were performed. RESULTS: The flap survival rate was 46.25% (8.12%) in the control group, 68.72% (7.00%) in the SD group, 57.03% (8.17%) in the FMES group and 80.66% (3.27%) in the HFP group. Immunohistologic analysis of CD 31+ cell in distal end of viable tissue procured seven days after flap elevation showed a significantly higher angiogenesis in SD group and HFP group. Western Blot results showed an increased expression of VEGF in SD group and HFP group. CONCLUSION: We have developed and fabricated a novel hybrid flap precondition (HFP) device combining foam-mediated external suction and non-surgical delay. The concept of HFP is proved to promote flap survival better than surgical delay.

Analysis of CD4+ T-helper-associated hub gene signature and immune dysregulation via RNA-sequencing data in a mouse tail model of lymphedema.

Background: T-helper cells play an essential role in the progression of lymphedema. This study aimed to explore the biological significance of T-helper cell-associated genes (THAGs) in a mouse tail model of lymphedema by RNA-sequencing (RNA-seq) data. Methods: The expression profiles of a murine model of secondary lymphedema were obtained from European Nucleotide Archive (ENA) database. Differentially expressed genes (DEGs) were screened and the enrichment analysis of DEGs was conducted. THAGs were constructed by crossing the T-helper-related gene sets obtained from Molecular Signatures Database with DEGs. Protein-protein interaction (PPI) network analysis was utilized to establish T-helper-associated hub genes (THAHGs). Single-sample gene set enrichment analysis (ssGSEA) was employed to decipher differences in immune cell infiltration. The correlation between THAHGs and immune infiltration was calculated by Pearson correlation analysis. Receiver operating characteristic (ROC) curves of THAHGs were drawn to evaluate their diagnostic properties. Additionally, potential drugs and upstream transcription factors (TFs) were predicted based on THAHGs. Results: Enrichment analysis showed that lymphedematous tissue presented higher activation of biological process (BP) of T-helper 1 (Th1), T-helper 2 (Th2), T-helper 17 (Th17). The immune infiltration analysis further calculated that the relative immune abundance of follicular B cells, memory B cells, M1 macrophage, and CD4+ Tm cells was significantly elevated while the relative immune abundance of neutrophils and plasma cells were down-regulated in lymphedema. We established a list of THAHGs consisting of eight hub genes, compassing Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, Cd74. THAHGs were shown to be significantly interrelated and related to immune infiltration by Pearson correlation analysis. ROC curves showcased that the area under curve (AUC) values of THAHGs were larger than 0.70. Gata3 was the most potential TF and thalidomide might be the immunoregulatory drug for lymphedema based on THAHGs. Conclusions: Biological pathways associated with T-helpers were significantly enriched in mouse lymphedema tissue. The relative immune infiltration abundance of M1 macrophage, CD4+ Tm cells, and T-helper cells was higher in the lymphedema group. Besides, we identified the THAHGs containing eight genes, namely, Cd4, Foxp3, Irf4, Ccr6, Il12rb1, Batf, Il1b, and Cd74. The THAHGs were closely correlated with immune infiltration results and with good diagnostic properties.

The Function of T Cell Immunity in Lymphedema: A Comprehensive Review.

Lymphedema is a debilitating disease characterized by extremity edema, fibroadipose deposition, impaired lymphangiogenesis, and dysfunctional lymphatics, often with lymphatic injury secondary to the treatment of malignancies. Emerging evidence has shown that immune dysfunction regulated by T cells plays a pivotal role in development of lymphedema. Specifically, Th1, Th2, Treg, and Th17 cells have been identified as critical regulators of pathological changes in lymphedema. In this review, our aim is to provide an overview of the current understanding of the roles of CD4+ T cells, including Th1, Th2, Treg, and Th17 subsets, in the progression of lymphedema and to discuss associated therapies targeting T cell inflammation for management of lymphedema.

A Computerized Recognition System to Assess Breast Asymmetry after Augmentation Mammaplasty.

BACKGROUND: Breast augmentation patients are often unaware of their preexisting breast asymmetry before surgery but discover it afterward, which leads to postoperative dissatisfaction and increases the reoperation rate. However, elaboration on how patients subjectively analyze breast asymmetry and the recognition thresholds were limited. METHODS: Two hundred female participants, including 100 patients 6 months postoperatively for primary augmentation mammaplasty and 100 preoperative patients, were recruited as two study groups. Self-assessments of breast asymmetry and objective measurements were taken. A computerized recognition experiment was constructed based on standardized three-dimensional models with different nipple-areola complex (NAC) and inframammary fold (IMF) asymmetry combinations. One hundred twenty-one three-dimensional models were generated and shown in random sequence. Participants responded whether they discovered breast asymmetry in each model. The recognition rate and 50% recognition thresholds of the asymmetry in NAC, IMF, lower pole length, volume, and their interrelations were calculated. RESULTS: Self-assessment of the postaugmentation group showed more precise distinguishing of NAC, IMF, and lower pole distance asymmetry than in the preaugmentation group. The 50% recognition thresholds of NAC and IMF level discrepancies were approximately 0.75 cm, with the IMF asymmetry identified with higher accuracy. When the NAC level discrepancy ranged from 0.0 to 1.25 cm, adjusting the IMF level discrepancy from 0.0 to 0.5 cm in the same direction lowered participants' recognition rates of breast asymmetry. CONCLUSIONS: Patients recognize their breast asymmetry issue more accurately after augmentation operations, despite improved parameters. In addition, adjusting the new IMF level, aligning with NAC discrepancy within 0.5 cm when treating mild NAC asymmetry, improved symmetric outcomes.

Postoperative Complications Following Prepectoral Versus Partial Subpectoral Implant-Based Breast Reconstruction Using ADM: A Systematic Review and Meta-analysis.

BACKGROUND: There is a paucity of evidence comparing the safety of prepectoral and partial subpectoral implant-based breast reconstruction using acellular dermal matrices (ADM). We performed a meta-analysis to evaluate the postoperative complications of the two approaches. METHODS: PubMed, EMBASE, Web of Science and Cochrane Library were searched to retrieve relevant articles. The rates of the complications were, respectively, pooled, and relative risk (RR) was estimated with 95% confidence intervals (CIs) to compare the incidence between the two cohorts. RESULTS: Ten articles reporting on 2667 breast reconstructions were eligible. The hematoma rate was lower in the prepectoral group (RR = 0.590, 95% CI 0.351-0.992). No significant difference was observed in terms of seroma (RR = 1.079, 95% CI 0.489-2.381), skin flap necrosis (RR = 0.936, 95% CI 0.587-1.493), infection (RR = 0.985, 95% CI 0.706-1.375), tissue expander/implant explantation (RR = 0.741, 95% CI 0.506-1.085), wound dehiscence (RR = 1.272, 95% CI 0.605-2.673), capsular contracture (RR = 0.939, 95% CI 0.678-1.300) and rippling (RR = 2.485, 95% CI 0.986-6.261). The RR of animation deformity for the prepectoral group compared with the subpectoral group was 0.040 (95% CI, 0.002-0.853). CONCLUSIONS: This systematic review suggested that with appropriate patient selection, prepectoral breast reconstruction could avoid animation deformity without incurring higher risk of early wound complications, capsular contracture or rippling than partial subpectoral breast reconstruction. Plastic surgeons should complete a comprehensive assessment of the patients before choosing appropriate surgical approaches in clinical practice. LEVEL OF EVIDENCE III: 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 .

Analysis of Patient-Reported Outcomes After Breast Reconstruction: A Retrospective Study.

OBJECTIVE: This study aimed to investigate the effects of surgical timing, procedure, and age, on complication rates, health-related quality of life, and postoperative satisfaction, in patients who underwent breast reconstruction. METHODS: The data of 80 patients who underwent breast reconstruction surgery between August 2004 and June 2018 were reviewed. Patients were grouped according to surgical timing, procedure, and age. The evaluation indicators included complications and BREAST-Q scores. The statistical methods used included the Mann-Whitney U test and analyses of variance and covariance. RESULTS: The incidence of complications was 15.0% (12/80). The complication rates were similar in each group ( P > 0.05). The postsurgical scores of patient satisfaction with breast, psychosocial well-being, and sexual well-being were higher than the presurgical scores ( P < 0.05). The postoperative psychosocial and sexual well-being scores of patients in the immediate group were higher than those in the delayed group ( P < 0.05). The satisfaction with the outcome in the abdominal flap group was higher than that in the other group, whereas the sexual well-being score of the abdominal flap group was lower than that of the other group ( P < 0.05). The scores of the postoperative physical well-being of the chest and abdomen in the younger group were higher than that in the older group ( P < 0.05). CONCLUSIONS: Breast reconstruction can significantly improve patients' health-related quality of life and satisfaction. Immediate breast reconstruction can reduce the adverse psychological and physical effects that breast loss exerts on patients, leading to better postoperative satisfaction. Patients who underwent breast reconstruction with abdominal flaps had higher postoperative satisfaction. Breast reconstruction in elderly patients was associated with considerable postoperative satisfaction.

How Do Positions of Nipple and Inframammary Fold Change After Autologous Breast Augmentation with Fat Grafting?

BACKGROUND: Breast augmentation with autologous fat grafting was widely used. However, it is unclear how does this kind of surgery affect the morphologic change of breast. This study aimed to explore the change of nipple and inframammary fold (IMF) levels, which are important aesthetic landmarks of breast that further explore whether this kind of surgery could correct the asymmetry of nipple and IMF. METHODS: Preoperative and postoperative measurements were performed in the patients who received fat grafting with or without fasciotomy. The position levels of nipple and IMF were measured. The preoperative and postoperative discrepancies and the difference of these levels after surgery were also calculated. RESULTS: As for the IMF asymmetry, in the fasciotomy plus fat grafting group, the asymmetry was significantly reduced after surgery, while there was no significant difference in the fat grafting group. As for the nipple asymmetry, fat grafting could not correct the asymmetry in both fasciotomy plus fat grafting group and fat grafting group. As for the morphological change after surgery, both nipple and IMF were descended significantly after surgery. The descending range of IMF in the preoperative higher group was larger than the preoperative lower group. On the preoperative IMF higher side, descending degree of IMF was significantly larger in the fasciotomy plus fat grafting group than fat grafting group. CONCLUSIONS: Fat grafting with fasciotomy can improve IMF asymmetry but cannot improve nipple asymmetry. Both IMF and nipple were lowered somehow after surgery, which might be related to the breast enlargement. 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.

Preoperative Three-Dimensional Measurement-Based Periareolar Augmentation Mastopexy: Indication and Breast Crown Approach.

SUMMARY: At present, there is no uniform and quantitative indication standard for periareolar augmentation mastopexy. The authors proposed an indication algorithm and a matched approach to delineate the outer circle, to optimize the result of this operation. Five parameters, including both implant and breast characteristics, were incorporated to form an indication algorithm based on three-dimensional measurement. The indication follows the principle that the circumference of the outer circle should be no more than two times the inner circle. To delineate the outer circle, a "crown" was made on the breast. The above approaches were used on patients who came for periareolar augmentation mastopexy from October of 2015 to January of 2019. Data analyzed included BREAST-Q score, areola diameter, the distance of the sternal notch to the nipple preoperatively and 1 year postoperatively, the distance of nipple elevation 1 year postoperatively, and complication and revision rates. A total of 28 breasts (14 patients) were included in this study. BREAST-Q scores 1-year postoperatively showed significant increases in Satisfaction with Breasts, Psychosocial Well-Being, and Sexual Well-Being ( p = 0.000). The mean areolar diameter preoperatively and postoperatively was 6.7 ± 1.2 cm and 4.6 ± 0.4 cm, respectively ( p = 0.000), and the mean sternal notch-to-nipple distance preoperatively and postoperatively was 22.2 ± 1.9 cm and 18.6 ± 1.0 cm, respectively ( p = 0.000), with an average nipple elevation of 3.2 ± 1.1 cm. The overall complication rate was 7.1 percent ( n = 2); both cases were areolar spreading. The overall revision rate was 0 percent. This preliminary study demonstrated the safety and efficacy of the indication and breast crown approach in reducing complication and revision rates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The Impact of Ammonium Chloride-Based Erythrocyte Lysis Process on Banked Adipose-Derived Stem Cells.

The safety of banked human adipose-derived stem cells (hADSCs) purified by 155 mM ammonium chloride (NH4Cl)-based erythrocyte lysis has not been evaluated. This study was conducted to determine the impact of NH4Cl-based erythrocyte lysis on the biological characteristics of cryopreserved hADSCs. Stromal vascular fractions (SVFs) were obtained from lipoaspirates and purified with NH4Cl-based erythrocyte lysis (lysis group) or without (nonlysis group). The hADSCs were freshly isolated (fresh group) from SVFs and/or cryopreserved for 2 weeks (cryo group). The morphologies, immunophenotypes, viability, apoptosis, and growth kinetics of each group were compared. The cell cycle and differentiation capacity assays were performed in both cryopreserved groups. All groups showed similar cell morphology, immunological phenotypes, and viability. However, the main effect of lysis and its interaction with cryopreservation were observed when early apoptosis was regarded as a dependent variable in two-way repeated-measures analysis of variance. After cryopreservation, significant growth retardation and S-phase fraction reduction were observed in lytic hADSCs compared with those in nonlytic hADSCs. No significant differences in the adipogenic and osteogenic differentiation capacities were found between the two groups. Although NH4Cl-based erythrocyte lysis did not affect the cell morphology, immunological phenotypes, viability, and adipogenic and osteogenic differentiation capacities of cryopreserved hADSCs, exposure to NH4Cl-based erythrocyte lysis or its synergistic action with cryopreservation may induce apoptosis and inhibit the proliferation and mitosis of cryopreserved hADSCs. These results indicate that NH4Cl-based erythrocyte lysis is not suitable for high-quality banked collection of hADSCs for future clinical applications. Further development of safe, convenient, and cost-effective purification methods of hADSCs is warranted.

Chest Wall Reconstruction in Male Poland Syndrome Patients with Endoscopic-Assisted Latissimus Dorsi Muscle Flap Transfer.

BACKGROUND: Pectoralis major absence generates chest wall deformity and always requires surgical intervention. This study aimed to introduce a technique to reconstruct the chest wall for male Poland Syndrome patients with endoscopic latissimus dorsi muscle (ELDM) flap via a single transverse axillary incision and evaluate its safety and effectiveness. METHODS: A prospective study was designed to recruit male Poland Syndrome candidates for ELDM chest reconstruction. By performing a short and hidden transaxillary incision, we created anterior chest wall pocket and transferred the latissimus dorsi muscle (LDM) flap to recontour the chest wall. Data for patient demographics, LDM flap dimension, operative time, and complications were collected. Upper extremity functional disabilities were evaluated by the disabilities of the arm, shoulder and hand (DASH) outcome questionnaire. Satisfaction with the outcome was measured by satisfaction with outcome subscale of the BREAST-Q questionnaire. RESULTS: This study recruited 11 eligible patients to receive ELDM chest wall reconstruction. ELDM flap harvesting averagely consumed 79.9 minutes. Without significant complications, all patients recovered uneventfully. Chest wall anomalies of different severity were corrected safely and effectively. The score of DASH was 3.7±3.3 preoperatively and 4.0±3.7 postoperatively with no statistically significant difference. The score of satisfaction with the outcome was 84.8±14.3. CONCLUSIONS: For chest wall anomalies of different severity in male Poland Syndrome patients, the ELDM technique provides a safe and efficient way to reconstruct the chest wall with a better aesthetic outcome, high satisfaction rate, and satisfactory upper limb function.

Is Pregnancy Following a TRAM or DIEP Flap Safe? A Critical Systematic Review and Meta-analysis.

BACKGROUND: Previous data were not conclusive on the safety of gestation in patients whose abdominal flaps were earlier harvested. We performed a meta-analysis to evaluate the abdominal wall complications and birth mode of pregnancy in post-TRAM or post-DIEP harvested individuals. METHODS: A literature search was performed using the PubMed, Embase, Scopus, and Google scholar database. Heterogeneity was statistically analyzed, and random effect models were applied. Publication bias was assessed by funnel plot. RESULTS: We included 25 papers that captured 56 patients giving birth to 69 healthy babies after elevation of abdominally based flaps, with a pooled abdominal complication rate of 0.00-0.09. The complication incidence in TRAM group was 0.01 (95% CI = [0.00-0.14%]) while 0.00 in the DIEP group (95% CI = [0.00-0.26%]). Discrepancies in incidence following unilaterally or bilaterally based TRAM flaps, following free or pedicled TRAM flaps, following primary sutured or mesh strengthened fascia, following MS free TRAM or conventional free TRAM could not be calculated as statistically significant. TRAM group and DIEP group patients had identical birth modes. CONCLUSIONS: The present meta-analysis did not detect evidence that abdominal walls with the prior harvest of abdominal flaps could affect the process of pregnancy or contraindicate vaginal delivery. No abdominal hernia or bulge occurred with post-DIEP pregnancies. However, such conclusions need to be substantiated by larger sample studies. LEVEL OF EVIDENCE III: 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 Table of Contents or online Instructions to Authors www.springer.com/00266 .

Balancing Nipple and Inframammary Fold in Transaxillary Augmentation Mammaplasty with Anatomical Implant: The 'NIMF' Classification and Surgical Algorithm.

BACKGROUND: This study aims to put forward a new classification of breast asymmetry based on the relative position of the nipple and inframammary fold (IMF) and propose a surgical algorithm of determining new IMF to address breast asymmetry in patients undergoing transaxillary augmentation mammaplasty, which is named as NIMF (nipple inframammary) classification and surgical algorithm. METHODS: Three hundred and forty-five patients received transaxillary augmentation mammaplasty with anatomical implants. Preoperative breast asymmetry was classified into four types. I: asymmetrical nipple with asymmetrical IMF in the same direction; II: symmetrical nipple with asymmetrical IMF; III: asymmetrical nipple with symmetrical IMF; IV: asymmetrical nipple with unapparent IMF. Surgical plans (3 plans for type I, II, IV while 5 plans for type III) to set the new IMF were provided for each patient, who chose one of them as the final surgical plan. Breast-Q and Likert scale were used to evaluate patient satisfaction and symmetry of breast preoperatively and 6 months postoperatively. RESULTS: The incidence of type I, II, III, IV was 30%, 15%, 13%, and 4%, respectively. Ninety-seven percent of patients with breast asymmetry chose plan C, which aimed to balance the relative position of nipple and IMF. Postoperative Breast-Q scores showed a significant rise compared with preoperative scores, but no statistical difference between plan C V.S. other plans. Patients with symmetrical preoperative breasts (Group A) had significantly higher postoperative Breast-Q scores than patients with asymmetrical preoperative breasts (Group B). In breast symmetry assessment, Group A had a significantly higher postoperative score than Group B, but the postoperative score was significantly lowered compared with the preoperative score in both Group A and B. CONCLUSION: The NIMF classification and surgical algorithm provide a systematic and scientific way to analyze and improve breast asymmetry, to achieve optimized patient satisfaction in transaxillary augmentation mammaplasty with anatomical implants. 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 Table of Contents or online Instructions to Authors www.springer.com/00266 .