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Background: It remains unknown whether the tumor stage at initial diagnosis and adjuvant treatments had any impacts on the long-term survival outcomes of patients with triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT)., Methods: Clinical stage II-III patients with TNBC who achieved pCR after NACT were identified from the Surveillance, Epidemiology, and End Results (SEER) program (SEER cohort) and the National Clinical Research Center for Cancer (Tianjin) in China (TMUCIH cohort). Survival analyses were conducted based on tumor stages and the types of adjuvant treatment received by the patients. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS)., Results: The TMUCIH cohort comprised 178 patients with a median follow-up of 55.5 months. Two and 3 patients experienced BCSS and OS events, respectively. The SEER cohort included 1218 patients with a median follow-up of 65.5 months, where 53 and 78 patients experienced BCSS and OS events, respectively. Patients diagnosed with stage III disease had significantly higher hazards of death compared to stage II disease (OS: hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.84-6.07; P < .001; BCSS: HR, 2.86; 95% CI, 1.38-5.92; P < .001). Adjuvant systemic and radiation therapy did not confer additional benefits to OS and BCSS., Conclusion: Tumor stage at initial diagnosis remains an independent predictor of long-term survival outcomes in patients with TNBC achieving pCR after NACT. Postoperative adjuvant chemotherapy and radiation therapy do not appear to provide additional benefit to their long-term prognosis., Competing Interests: Disclosure The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The oncologic safety of preserving the pectoralis major fascia (PMF) in patients with breast cancer remains controversial. In this study, we aimed to determine the impact of preserving the PMF on long-term oncologic outcomes in patients with breast cancer treated with immediate implant-based breast reconstruction (IBBR) following conservative mastectomy., Methods: We selected women with early-stage breast cancer who underwent conservative mastectomy and submuscular IBBR in our center during 2014-2019. The propensity score matching method was used to create well-balanced fascia-preserved and fascia-removed groups. Locoregional recurrence-free survival (LRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the fascia-preserved and fascia-removed groups., Results: After matching, there were 219 patients in each group. The mean follow-up time was 64.8 ± 18.1 months for the fascia-preserved group and 64.9 ± 18.4 months for the fascia-removed group. There were no significant differences between the groups in terms of LRFS (91.3% vs. 93.8%; p = 0.818), DMFS (94.0% vs. 92.3%; p = 0.056), DFS (89.9% vs. 88.4%; p = 0.261), and OS (95.8% vs. 95.4%; p = 0.783) rates. In the fascia-preserved group, 61.5% of the locoregional recurrence events occurred within 2 years after surgery., Conclusion: Preservation of the PMF did not significantly impact the long-term oncologic outcomes in patients with breast cancer who underwent conservative mastectomy and IBBR. The PMF might be safely preserved in patients without suspicious tumor invasion into this fascia., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: To establish whether increased variability in macular thickness in neovascular age-related macular degeneration (nAMD) patients affects visual outcomes in clinical practice DESIGN: Retrospective cohort study PARTICIPANTS: Treatment-naive nAMD patients studied over 24 months METHODS: Central subfield thickness (CST) values from optical coherence tomography were collected quarterly from baseline to 24 months, and standard deviations (SDs) were calculated. The relationship was modeled with mixed-effects regression between CST SD and 24-month change in visual acuity (VA). Linear regression modeling determined predictors of CST SD., Results: A total of 422 eyes with nAMD were studied. Baseline and 24-month CST values (mean ± SD) were 331.2 ± 97.6 and 253.4 ± 53.6 μm (Δ = -77.8 ± 104.7 μm, p < 0.001), with CST SD across 24 months of 42.0 ± 32.8 μm. Baseline and 24-month VA were 58.8 ± 19.2 and 62.4 ± 20.6 Early Treatment of Diabetic Retinopathy Study letters (Δ = +3.7 ± 20.8 letters, p = 0.008). CST SD over 24 months was a statistically significant negative predictor of 24-month change in VA (-15.41 [-20.98, -9.83] letters per 100 μm, p < 0.001). Quartile analysis of 24-month VA by CST SD showed a +11.2-letter difference between the first and last quartiles (p < 0.001). Baseline CST was a predictor of 24-month CST SD (24.88 [22.69, 27.06] μm per 100 μm, p < 0.001)., Conclusions: Higher macular thickness fluctuations are related to poorer visual outcomes at 24 months in patients with nAMD treated with anti-vascular endothelial growth factor injections. Macular thickness variability may be an important prognostic factor of visual outcomes in nAMD eyes., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate visual acuity (VA) outcomes, prognostic factors, and changes in disease severity in patients with age-related macular degeneration (AMD) undergoing cataract surgery., Design: Retrospective cohort study PARTICIPANTS: Patients with AMD or healthy control patients who underwent cataract surgery between 2012 and 2017., Methods: Eyes were categorized into 3 AMD groups-intermediate AMD (iAMD), fovea-involving geographic atrophy (GA), neovascular AMD (nAMD)-and 3 preoperative VA-matched control groups (iAMDc), fovea-involving geographic atrophy control (GAc), neovaascular AMD control (nAMDc)., Results: We compared 216 iAMD, 35 GA, and 184 nAMD eyes with 130, 31, and 129 controls. At postoperative month 12 (POM12), VA increased significantly in iAMD and nAMD (+10.1 ± 14.5 and +9.7 ± 18.9 letters, p < 0.001), but not in GA (p = 0.68). All control groups showed significant VA gains (iAMDc: +17.1 ± 9.7, GAc: +30 ± 12.9, and nAMDc: +26.4 ± 15.6 letters, p < 0.001). For AMD groups, POM12 VA and gain in VA were significantly lower than that of controls (p < 0.01), and better preoperative VA predicted smaller VA gains (p ≤ 0.007). Longer duration of AMD in iAMD, ellipsoid zone disruption in nAMD, and lower central subfield thickness in GA were associated with poorer VA outcomes (p < 0.05). Development of nAMD occurred in 8 iAMD eyes and was associated with longer duration of disease (p = 0.001). For nAMD eyes, injection frequency did not vary between the 12-month pre- and postoperative periods (p = 0.051)., Conclusions: Cataract surgery improves VA for patients with iAMD and nAMD, albeit not to the level of those without retinal pathology. Preoperative VA, AMD duration, and optical coherence tomography parameters may be important prognostic factors for cataract surgery in patients with AMD., (Copyright © 2021 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Purpose: This study characterizes the association of risk factors including race, ethnicity, and insurance status with presenting visual acuity (VA) and diabetic retinopathy (DR) severity in patients initiating treatment with anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME)., Design: Retrospective, cross-sectional study., Participants: The Academy Intelligent Research in Sight (IRIS) Registry database was queried for patients who initiated anti-VEGF injection treatment for DME between 2012 and 2020 (n = 203 707)., Methods: Multivariate regression analyses were conducted to understand how race, ethnicity, insurance status, and geographic location were associated with baseline features., Main Outcome Measures: Visual acuity and DR severity., Results: Patients on Medicare and private insurance presented with higher baseline VA compared with patients on Medicaid (median of 2.31 and 4.17 greater Early Treatment Diabetic Retinopathy Scale [ETDRS] letters, respectively P < 0.01). White and non-Hispanic patients presented with better VA compared with their counterparts (median of 0.68 and 2.53 greater ETDRS letters, respectively; P < 0.01). Black and Hispanic patients presented with a worse baseline DR severity compared with White and non-Hispanic patients (odds ratio, 1.23 and 1.71, respectively; P < 0.01)., Conclusions: There are ethnic and insurance-based disparities in VA and disease severity upon initiation of anti-VEGF therapy for DME treatment. Public health initiatives could improve timely initiation of treatment., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To assess age-related differences at baseline and treatment outcomes in patients with retinal vein occlusion (RVO) and macular edema treated with anti-vascular endothelial growth factor (VEGF) therapy DESIGN: Single-centre retrospective chart review., Participants: 295 treatment-naïve RVO patients., Methods: 295 RVO patients included were separated into age quartiles: group A (22-61 years), group B (62-70 years), group C (71-79 years), and group D (80-95 years). Outcomes including central subfield thickness (CST), cubic volume, cubic average thickness, and visual acuity (VA) were collected at baseline and at 6 and 12 months after treatment. The primary outcome of the study was the CST at 12 months after anti-VEGF therapy., Results: Mean baseline CST for groups A, B, C, and D was 406.3 ± 161.2 μm, 463.4 ± 165.5 μm, 470.6 ± 187 μm, and 427.3 ± 187.2 μm, respectively. No significant differences in CST were observed between groups at baseline, 6 months, or 12 months (p ≥ 0.08). Mean baseline VA for groups A, B, C, and D was 55.8 ± 19.5, 54.4 ± 19.8, 54.7 ± 19, and 51.4 ± 20.4 Early Treatment Diabetic Retinopathy letters, respectively. VA did not differ significantly between age groups at baseline, 6 months, or 12 months (p ≥ 0.06)., Conclusions: The presentation of RVO and the visual outcomes of anti-VEGF therapy do not vary based on age., (Copyright © 2020 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Ataxia, characterized by uncoordinated movement, is often found in patients with cerebellar hemorrhage (CH), leading to long-term disability without effective management. Microglia are among the first responders to CNS insult. Yet the role and mechanism of microglia in cerebellar injury and ataxia after CH are still unknown. Using Ki20227, an inhibitor for colony-stimulating factor 1 receptor which mediates the signaling responsible for the survival of microglia, we determined the impact of microglial depletion on cerebellar injury and ataxia in a murine model of CH. Microglial depletion reduced cerebellar lesion volume and alleviated gait abnormality, motor incoordination, and locomotor dysfunction after CH. Suppression of CH-initiated microglial activation with minocycline ameliorated cerebellum infiltration of monocytes/macrophages, as well as production of proinflammatory cytokines and chemokine C-C motif ligand-2 (CCL-2) that recruits monocytes/macrophages. Furthermore, both minocycline and bindarit, a CCL-2 inhibitor, prevented apoptosis and electrophysiological dysfunction of Purkinje cells, the principal neurons and sole outputs of the cerebellar cortex, and consequently improved ataxia-like motor abnormalities. Our findings suggest a detrimental role of microglia in neuroinflammation and ataxic motor symptoms after CH, and pave a new path to understand the neuroimmune mechanism underlying CH-induced cerebellar ataxia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Breast cancer is the most common cancer among women worldwide. Chemoresistance remains to be a considerable obstacle in breast cancer therapy and it is often involves dysregulation of a variety of microRNAs (miRNAs). miR-485-5p functions as a tumor suppressor in several types of human cancers. However, its role in breast cancer chemosensitivity have not been determined. In the present study, we demonstrated that overexpression of miR-485-5p suppresses breast cancer progression and enhances chemosensitivity both in vitro and in vivo. Further study demonstrated that miR-485-5p directly targeted the 3'-untranslated region of survivin and overexpression of survivin overcomes the miR-485-5p induced effects on breast cancer. In conclusion, our study identified that miR-485-5p suppresses cancer progression and enhances the chemosensitivity by targeting survivin. Targeting survivin by miR-485-5p may provide a potential approach to reverse chemosensitivity in breast cancer cells., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The transcription factor forkhead box D3 (FOXD3) plays an important role in the development of neural crest and gastric cancer cells. However, the function and mechanisms of FOXD3 in the breast tumorigenesis and progression is still limited. Here, we report that FOXD3 is a tumor suppressor of breast cancer tumorigenicity and aggressiveness. We found that FOXD3 is down-regulated in breast cancer tissues. Patients with low FOXD3 expression have a poor outcome. Depletion of FOXD3 expression promotes breast cancer cell proliferation and invasion in vitro, whereas overexpression of FOXD3 inhibits breast cancer cell proliferation and invasion both in vitro and in vivo. In addition, depletion of FOXD3 is linked to epithelial-mesenchymal transition (EMT)-like phenotype. Our results indicate FOXD3 exhibits tumor suppressive activity and may be useful for breast therapy., (Copyright © 2014 Elsevier Inc. All rights reserved.)