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Background: Metastasis remains the leading cause of mortality among colorectal cancer (CRC) patients. Identification of new metastasis-related genes are critical to improve colorectal cancer prognosis. Methods: Data on mRNA expression in metastatic and primary CRC was obtained from the Gene Expression Omnibus (GEO) database, including GSE81986, GSE41568, GSE71222, GSE21510, and GSE14333. Additionally, data concerning mRNA expression in colon cancer (COAD) and adjacent normal tissues were acquired from The Cancer Genome Atlas (TCGA) database. Hub genes were identified by weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis. Moreover, we assessed the impact of hub gene expression on both overall survival (OS) and disease-free survival (DFS) in patients and identified ZG16 as a potential target. We generated CRC cell lines transfected with lentivirus OE-ZG16 to investigate proliferation, invasion, and migration in vitro. To further elucidate the involvement of ZG16, we utilized gene set enrichment analysis (GSEA) to identify enriched pathways, which were subsequently validated via Western blot analysis. Results: Five datasets containing primary and metastatic CRC samples from GEO database and CRC samples from TCGA database were included in this study and 29 hub genes were identified by WGCNA and differentially expressed gene (DEG) analysis. Low expression of the hub genes (CLCA1 and ZG16) was associated with poor DFS and OS. We confirmed the low expression of ZG16 in CRC using external database and IHC analysis at both transcriptional and protein levels. In addition, the expression of ZG16 was notably elevated in NCM460 cells in comparison to CRC cell lines. The overexpression of ZG16 in CRC cells has been shown to inhibit the proliferation, invasion, and migration of CRC cells. Furthermore, the overexpression of ZG16 has been found to suppress the activation of the epithelial-mesenchymal transition (EMT) and Wnt/ß-catenin signaling pathways in CRC. Conclusion: ZG16 may serve as a promising therapeutic target for metastatic CRC treatment.
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BACKGROUND: The ability to determine severity of encephalopathy is crucial for early neuroprotective therapies and for predicting neurodevelopmental outcome. The objective of this study was to assess a novel brain state of newborn (BSN) trend to distinguish newborns with presence of hypoxic ischemic encephalopathy (HIE) within hours after birth and predict neurodevelopmental outcomes at 2 years of age. METHOD: This is a prospective cohort study of newborns at 36 weeks' gestation or later with and without HIE at birth. The Total Sanart Score (TSS) was calculated based on a modified Sarnat exam within 6 h of life. BSN was calculated from electroencephalogram (EEG) measurements initiated after birth. The primary outcome at 2 year of age was a diagnosis of death or disability using the Bayley Scales of Infant Development III. RESULTS: BSN differentiated between normal and abnormal neurodevelopmental outcomes throughout the entire recording period from 6 h of life. Additionally, infants with lower BSN values had higher odds of neurodevelopmental impairment and HIE. BSN distinguished between normal (n = 86) and HIE (n = 46) and showed a significant correlation with the concomitant TSS. CONCLUSION: BSN is a sensitive real-time marker for monitoring dynamic progression of encephalopathy and predicting neurodevelopmental impairment. IMPACT: This is a prospective cohort study to investigate the ability of brain state of newborn (BSN) trend to predict neurodevelopmental outcome within the first day of life and identify severity of encephalopathy. BSN predicts neurodevelopmental outcomes at 2 years of age and the severity of encephalopathy severity. It also correlates with the Total Sarnat Score from the modified Sarnat exam. BSN could serve as a promising bedside trend aiding in accurate assessment and identification of newborns who may benefit from additional neuroprotection therapies.
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Network meta-analysis, also known as mixed treatments comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis. Despite the growing popularity of network metaanalysis within comparative effectiveness research, it comes with potential challenges. For example, within-study correlations among treatment comparisons are rarely reported in the published literature. Yet, these correlations are pivotal for valid statistical inference. As demonstrated in earlier studies, ignoring these correlations can inflate mean squared errors of the resulting point estimates and lead to inaccurate standard error estimates. This paper introduces a composite likelihood-based approach that ensures accurate statistical inference without requiring knowledge of the within-study correlations. The proposed method is computationally robust and efficient, with substantially reduced computational time compared to the state-of-the-science methods implemented in R packages. The proposed method was evaluated through extensive simulations and applied to two important applications including a network meta-analysis comparing interventions for primary open-angle glaucoma, and another comparing treatments for chronic prostatitis and chronic pelvic pain syndrome.
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Multivariate network meta-analysis has emerged as a powerful tool in evidence synthesis by incorporating multiple outcomes and treatments. Despite its advantages, this method comes with methodological challenges, such as the issue of unreported within-study correlations among treatments and outcomes, which potentially lead to misleading conclusions. In this paper, we proposed a calibrated Bayesian composite likelihood approach to overcome this limitation. The proposed method eliminated the need to specify a full likelihood function while allowing for the unavailability of within-study correlations among treatments and outcomes. Additionally, we developed a hybrid Gibbs sampler algorithm along with the Open-Faced Sandwich post-sampling adjustment to enable robust posterior inference. Through comprehensive simulation studies, we demonstrated that the proposed approach yielded unbiased estimates while maintaining coverage probabilities close to the nominal level. Furthermore, we implemented the proposed method on two real-world network meta-analysis datasets; one comparing treatment procedures for the root coverage and another comparing treatments for anaemia in chronic kidney disease patients.
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PURPOSE: Ventilatory constraints are common during exercise in children, but the effects of obesity and sex are unclear. The purpose of this study was to investigate the effects of obesity and sex on ventilatory constraints (i.e., expiratory flow limitation (EFL) and dynamic hyperinflation) during a maximal exercise test in children. METHODS: Thirty-four 8-12-year-old children without obesity (18 females) and 54 with obesity (23 females) completed pulmonary function testing and maximal cardiopulmonary exercise tests. EFL was calculated as the overlap between tidal flow-volume loops during exercise and maximal expiratory flow-volume loops. Dynamic hyperinflation was calculated as the change in inspiratory capacity from rest to exercise. RESULTS: Maximal minute ventilation was not different between children with and without obesity. Average end-inspiratory lung volumes (EILV) and end-expiratory lung volumes (EELV) were significantly lower during exercise in children with obesity (EILV: 68.8 ± 0.7%TLC; EELV: 41.2 ± 0.5%TLC) compared with children without obesity (EILV: 73.7 ± 0.8%TLC; EELV: 44.8 ± 0.6%TLC; P < 0.001). Throughout exercise, children with obesity experienced more EFL and dynamic hyperinflation compared with those without obesity (P < 0.001). Also, males experienced more EFL and dynamic hyperinflation throughout exercise compared with females (P < 0.001). At maximal exercise, the prevalence of EFL was similar in males with and without obesity, however the prevalence of EFL in females was significantly different with 57% of females with obesity experiencing EFL compared with 17% of females without obesity (P < 0.05). At maximal exercise, 44% of children with obesity experienced dynamic hyperinflation compared with 12% of children without obesity (P = 0.002). CONCLUSIONS: Obesity in children increases the risk of developing mechanical ventilatory constraints such as dynamic hyperinflation and EFL. Sex differences were apparent with males experiencing more ventilatory constraints compared with females.
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BACKGROUND: Evaluation of the impact on mother-to-child transmission (MTCT) of a HBV-prevention program that incorporates maternal antiviral prophylaxis is hindered by the limited availability of real-world data. METHODS: This study analyzed data on maternal HBV screening, neonatal immunization, and post-vaccination serologic testing (PVST) for HBsAg among at-risk infants born to HBV carrier mothers from the National Immunization Information System during 01/01/2008-31/12/2022. Through linkage with the National Health Insurance Database, information of maternal antiviral therapy was obtained. Multivariate logistic regression was performed to explore MTCT risk in relation to infant-mother characteristics and prevention strategies. RESULTS: Totally, 2,460,218 deliveries with maternal HBV status were screened. Between 2008 and 2022, the annual HBsAg and HBeAg seropositivity rates among native pregnant women aged 15-49 years decreased from 12.2% to 2.6% and from 2.7% to 0.4%, respectively (p for both trends < 0.0001). Among the 22,859 at-risk infants undergoing PVST, the MTCT rates differed between infants born to HBsAg-positive/HBeAg-negative and HBeAg-positive mothers (0.75% and 6.33%, respectively; p < 0.001). The MTCT rate was 1.72% (11/641) for infants born to HBeAg-positive mothers with antiviral prophylaxis. MTCT risk increased with maternal HBeAg-positivity (OR 9.29, 6.79-12.73) and decreased with maternal antiviral prophylaxis (OR 0.28, 0.16-0.49). For infants with maternal HBeAg-positivity, MTCT risk was associated with mothers born in the immunization era (OR 1.40, 1.17-1.67). CONCLUSIONS: MTCT was related to maternal HBeAg-positivity and effectively prevented by maternal prophylaxis in the immunized population. At-risk infants born to maternal vaccinated cohorts might possibly pose further risk.
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Little is known about whether body composition changes differently between children with and without obesity following 1 year of nonintervention. Therefore, we investigated body composition in early pubescent children (8-12 yr) with and without obesity before and after a period of 1 year of nonintervention. Early pubescent children (8-12 yr; Tanner stage ≤ 3) with (body mass index, BMI ≥ 95th percentile) and without obesity (15th < BMI < 85th percentile) were recruited. At baseline, 88 children (n = 25 without obesity) completed dual-energy X-ray absorptiometry imaging (DXA) for body composition measurements [%body fat, fat mass, fat-free mass (FFM)]. One year later, 47 participants (n = 15 without obesity) returned for repeat testing. The children without obesity were older (11.0 ± 1.0 vs. 10.0 ± 1.2 yr; means ± SD) (P = 0.013). There was no group difference in height, and both groups increased in height similarly after 1 year (147.7 ± 8.9 to 154.5 ± 9.2 cm without vs. 145.6 ± 5.8 to 152.5 ± 5.9 cm with obesity) (P < 0.001). Weight was greater (P < 0.001) in children with obesity at baseline as was the increase in weight after 1 yr (9.25 vs. 5.82 kg) (interaction, P = 0.005). Fat mass increased by 4.4 kg in children with obesity and by 1.1 kg in children without obesity (interaction, P < 0.001). However, there was no difference in fat-free mass between those with and without obesity at baseline (29.9 ± 5.9 vs. 31.6 ± 4.8 kg) (P = 0.206) with both groups increasing similarly over 1 year (gain of 4.87 vs. 4.85 kg with and without obesity, respectively). Without intervention, the increase in fat mass is four times greater in children with obesity after 1 year as compared with children without obesity.NEW & NOTEWORTHY Little is known about changes in body composition in children with and without obesity following 1 year of nonintervention. We report that without intervention, fat mass gain is significantly greater in children with obesity after 1 year compared with those without obesity. Body mass index (BMI) and %body fat measurements after 1 year yielded no significant increase suggesting that BMI and %fat alone are not suitable measures for tracking changes in adiposity among children.
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Body Composition , Obesity , Child , Humans , Body Mass Index , Adiposity , Adipose Tissue , Absorptiometry, Photon/methodsABSTRACT
Taiwan provided several COVID-19 vaccine platforms: mRNA (BNT162b2, mRNA-1273), adenoviral vector-based (AZD1222), and protein subunit (MVC-COV1901). After Taiwan shifted from its zero-COVID strategy in April 2022, population-based evaluation of vaccine effectiveness (VE) became possible. We conducted an observational cohort study of 21,416,151 persons to examine VE against SARS-CoV-2 infection, moderate and severe illness, and death during March 22, 2021-September 30, 2022. After adjusting for age and sex, we found that persons who completed 3 vaccine doses (2 primary, 1 booster) or received MVC-COV1901 as the primary series had the lowest hospitalization incidence (0.04-0.20 cases/100,000 person-days). We also found 95.8% VE against hospitalization for 3 doses of BNT162b2, 91.0% for MVC-COV1901, 81.8% for mRNA-1273, and 65.7% for AZD1222, which had the lowest overall VE. Our findings indicated that protein subunit vaccines provide similar protection against SARS-CoV-2---associated hospitalization as mRNA vaccines and can inform mix-and-match vaccine selection in other countries.
Subject(s)
COVID-19 , Humans , 2019-nCoV Vaccine mRNA-1273 , BNT162 Vaccine , ChAdOx1 nCoV-19 , Cohort Studies , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , SARS-CoV-2/genetics , Taiwan/epidemiology , Vaccine Efficacy , Male , FemaleABSTRACT
In a recent systematic review, Bastos et al. (Ann Intern Med. 2021;174(4):501-510) compared the sensitivities of saliva sampling and nasopharyngeal swabs in the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by assuming a composite reference standard defined as positive if either test is positive and negative if both tests are negative (double negative). Even under a perfect specificity assumption, this approach ignores the double-negative results and risks overestimating the sensitivities due to residual misclassification. In this article, we first illustrate the impact of double-negative results in the estimation of the sensitivities in a single study, and then propose a 2-step latent class meta-analysis method for reevaluating both sensitivities using the same published data set as that used in Bastos et al. by properly including the observed double-negative results. We also conduct extensive simulation studies to compare the performance of the proposed method with Bastos et al.'s method for varied levels of prevalence and between-study heterogeneity. The results demonstrate that the sensitivities are overestimated noticeably using Bastos et al.'s method, and the proposed method provides a more accurate evaluation with nearly no bias and close-to-nominal coverage probability. In conclusion, double-negative results can significantly impact the estimated sensitivities when a gold standard is absent, and thus they should be properly incorporated.
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COVID-19 , Humans , COVID-19/diagnosis , SARS-CoV-2 , Negative Results , Saliva , NasopharynxABSTRACT
OBJECTIVES: COVID-19, since its emergence in December 2019, has globally impacted research. Over 360 000 COVID-19-related manuscripts have been published on PubMed and preprint servers like medRxiv and bioRxiv, with preprints comprising about 15% of all manuscripts. Yet, the role and impact of preprints on COVID-19 research and evidence synthesis remain uncertain. MATERIALS AND METHODS: We propose a novel data-driven method for assigning weights to individual preprints in systematic reviews and meta-analyses. This weight termed the "confidence score" is obtained using the survival cure model, also known as the survival mixture model, which takes into account the time elapsed between posting and publication of a preprint, as well as metadata such as the number of first 2-week citations, sample size, and study type. RESULTS: Using 146 preprints on COVID-19 therapeutics posted from the beginning of the pandemic through April 30, 2021, we validated the confidence scores, showing an area under the curve of 0.95 (95% CI, 0.92-0.98). Through a use case on the effectiveness of hydroxychloroquine, we demonstrated how these scores can be incorporated practically into meta-analyses to properly weigh preprints. DISCUSSION: It is important to note that our method does not aim to replace existing measures of study quality but rather serves as a supplementary measure that overcomes some limitations of current approaches. CONCLUSION: Our proposed confidence score has the potential to improve systematic reviews of evidence related to COVID-19 and other clinical conditions by providing a data-driven approach to including unpublished manuscripts.
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COVID-19 , Humans , Systematic Reviews as Topic , Research Design , PubMed , PandemicsABSTRACT
OBJECTIVES: Impaired linear growth is a known complication of pediatric inflammatory bowel disease (IBD), but the use of growth hormone (GH) in this population is not well-described. The primary aim of this study is to determine whether growth hormone use in pediatric IBD leads to improved height outcomes. METHODS: This was a retrospective chart review of patients with IBD aged 0-21 years followed at a single center between 2018 and 2021 treated with at least 1 year of GH. Records collected included demographics, IBD phenotype, IBD disease activity scores, medications, weight z-score, height z-score, bone age, and details of GH therapy including testing for GH deficiency. The primary outcome measure was change in height z-score after 1 year of GH treatment. RESULTS: Forty-six patients were identified and 18 were excluded. Of the 28 patients included (7 female; 25.0â¯%), 26 (92.9â¯%) had a diagnosis of Crohn's disease (CD) and 2 (7.1â¯%) had ulcerative colitis (UC). The mean (SD) age at GH initiation was 9.6 (3.4) years. Among all participants, there was a significant mean difference in height z-score from baseline to 1 year on therapy (-2.25 vs. -1.50, respectively; difference, 0.75; 95â¯% CI, 0.56 to 0.94; p<0.001). Among the 19 subjects that completed GH therapy there was a significant mean difference between baseline and final height z-scores (-2.41 vs. -0.77, respectively; difference, 1.64; 95â¯% CI, 1.30 to 1.98; p<0.001). CONCLUSIONS: GH use was associated with improved height outcomes. The pediatric IBD patients in this cohort had significant improvements in height z-scores both after one year on therapy and at completion of GH therapy.
Subject(s)
Crohn Disease , Human Growth Hormone , Inflammatory Bowel Diseases , Humans , Child , Female , Growth Hormone/therapeutic use , Retrospective Studies , Human Growth Hormone/therapeutic use , Inflammatory Bowel Diseases/drug therapy , Crohn Disease/drug therapyABSTRACT
We investigated whether older adults (OA) with obesity are more likely to have dyspnea compared with OA without obesity, and whether OA with obesity are at a greater risk of having dyspnea compared with middle-aged (MA) and younger adults (YA) with obesity. We obtained de-identified data from the TriNetX UT Southwestern Medical Center database. We identified obesity and dyspnea using ICD-10-CM codes E66 and R06.0, respectively. Patients were separated into three age groups: OA, (65-75 y.o.), MA (45-55 y.o.), and YA (25-35 y.o). Within these groups, those with and without obesity or dyspnea were identified for analysis. The risk of dyspnea was greater in OA (risk ratio: 3.64), MA (risk ratio: 3.52), and YA (risk ratio: 2.76) with obesity compared with age-matched patients without obesity (all p < 0.01). The risk of dyspnea was greater in OA and MA with obesity compared with YA with obesity (both p < 0.001 vs. YA). These findings suggest that clinicians should consider obesity as an independent risk factor for dyspnea.
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BACKGROUND: There is a critical need for development of physiological biomarkers in infants with birth asphyxia to identify the physiologic response to therapies in real time. This is an ancillary single site study of the High-Dose Erythropoietin for Asphyxia and Encephalopathy (Wu et al., 2022 [1]) to measure neurovascular coupling (NVC) non-invasively during an ongoing blinded randomized trial. METHODS: Neonates who randomized in the HEAL enrolled at a single-center Level III Neonatal Intensive Care Unit were recruited between 2017 and 2019. Neurodevelopmental impairment was blinded and defined as any of the following: cognitive score <90 on Bayley Scales of Infant Toddler Development, third edition (BSID-III), Gross Motor Function Classification Score (GMFCS) ≥1. RESULTS: All twenty-seven neonates enrolled in HEAL were recruited and 3 died before complete recording. The rank-based analysis of covariance models demonstrated lack of difference in NVC between the two groups (Epo versus Placebo) that was consistent with the observed lack of effect on neurodevelopmental outcomes. CONCLUSION: We demonstrate no difference in neurovascular coupling after Epo administration. These findings are consistent with overall negative trial results. Physiological biomarkers can help elucidate mechanisms of neuroprotective therapies in real time in future trials.
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Asphyxia Neonatorum , Erythropoietin , Hypoxia-Ischemia, Brain , Neurovascular Coupling , Infant, Newborn , Infant , Humans , Asphyxia , Neuroprotection , Erythropoietin/therapeutic use , Biomarkers , Hypoxia-Ischemia, Brain/drug therapyABSTRACT
Background Endovascular intervention of femoropopliteal chronic total occlusions (CTOs) is technically more complex. However, there is lack of comparative analysis between CTO and non-CTO femoropopliteal interventions. Methods and Results We report procedural details and outcomes of patients treated for femoropopliteal CTO and non-CTO lesions in the XLPAD (Excellence in Peripheral Artery Disease) registry (NCT01904851) between 2006 and 2019. Primary outcomes were procedural success and 1-year major adverse limb events, a composite of all-cause death, target limb revascularization, or major amputation. Analysis included 2895 patients (CTO: n=1516 patients; non-CTO: n=1379 patients) with 3658 lesions (CTO: n=1998 lesions; non-CTO: n=1660 lesions). Conventional balloon angioplasty (20.86% versus 33.48%, P<0.001) or drug-coated balloon angioplasty (1.26% versus 2.93%, P<0.001) were more frequent in the non-CTO group, whereas bare-metal stents (28.09% versus 20.22%, P<0.001) or covered stents (4.08% versus 1.83%, P<0.001) were more frequent in the CTO group. Debulking procedures were more commonly performed in the non-CTO group (41.44% versus 53.13%, P<0.001), despite a similar degree of calcification between the 2 groups. Procedural success was higher in the non-CTO group (90.12% versus 96.79%, P<0.001). Procedural complications were higher in the CTO group (7.21% versus 4.66%, P=0.002), mainly due to excess distal embolization (1.5% versus 0.6%, P=0.015). Adjusted 1-year major adverse limb events were higher in the CTO group (22.47% versus 18.77%, P=0.019), driven mainly by target limb revascularization (19.00% versus 15.34%, P=0.013). Conclusions Procedural success is lower for endovascular treatment of femoropopliteal CTO compared with non-CTO lesions. CTO lesions are associated with higher rates of periprocedural complications and reinterventions after 1 year.
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Peripheral Arterial Disease , Popliteal Artery , Humans , Popliteal Artery/diagnostic imaging , Popliteal Artery/surgery , Treatment Outcome , Femoral Artery/diagnostic imaging , Femoral Artery/surgery , Peripheral Arterial Disease/therapy , Registries , Chronic Disease , Vascular PatencyABSTRACT
Rationale and Objective: Serum magnesium levels have been inversely yet inconsistently associated with cardiovascular (CV) outcomes. In this study, we examined the association of serum magnesium levels with CV outcomes in the Systolic Blood Pressure Intervention Trial (SPRINT) participants. Study Design: Case-control post hoc analysis of SPRINT. Setting & Participants: A total of 2,040 SPRINT participants with available serum samples at baseline level were included in this study. Case participants (n = 510) who experienced a CV event during the SPRINT observation period (median follow-up of 3.2 years) and control participants (n = 1,530) without CV events were sampled in a 1:3 ratio for measurements of serum magnesium level at baseline and 2-year follow-up. Predictors: Baseline serum magnesium levels and 2-year percentage change in serum magnesium levels (ΔSMg). Outcome: SPRINT primary composite CV outcome. Analytical Approach: Multivariable conditional logistic regression analysis, accounting for matching factors, was used to evaluate the association of baseline and ΔSMg with CV outcomes. Individual matching of cases and controls was based on the SPRINT treatment arm allocation (standard vs intensive) and prevalence of chronic kidney disease (CKD). Results: The median serum magnesium level at baseline was similar among the case and control groups. In a fully adjusted model, each standard deviation (SD) (0.18 mg/dL) higher of the baseline serum magnesium level was independently associated with a lower risk for composite CV outcomes in all study participants (adjusted odds ratio 95% CI, 0.79 [0.70-0.89]). This association was similar when serum magnesium levels were analyzed in quartiles but dissipated in the standard (vs intensive) arm of SPRINT (0.88 [0.76-1.02] vs 0.65 [0.53-0.79], respectively; Pinteraction = 0.06). The presence or absence of CKD at baseline did not modify this association. ΔSMg was not independently associated with CV outcomes occurring after 2 years. Limitations: ΔSMg was small in magnitude, limiting effect size. Conclusions: Higher baseline serum magnesium levels were independently associated with reduced risk for CV outcomes in all study participants, but ΔSMg was not associated with CV outcomes.
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In this work, we aim to fabricate a highly stable and flexible perovskite paper photodetector based on a Zn-doped MA0.6FA0.4PbI3 perovskite and CNC. The paper photodetector has been successfully synthesized by the vacuum filtration method and deposited with interdigitated electrodes. The paper photodetector exhibits a significant photoresponse with a responsivity of 0.23 A W-1 under 650 nm light irradiation when operated at 5 V. The stability of the paper photodetector has also been tested and it shows high photoresponse after 30 days under ambient conditions. Therefore, this paper photodetector holds promise for developing efficient, stable, and flexible optoelectronic devices in the future.
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PURPOSE: Aspirin (ASA) use has been correlated with improved outcomes in high-risk patients at risk for distant metastases. Breast cancer (BC) patients with residual disease, particularly nodal disease (ypN +) after neoadjuvant chemotherapy (NAC), are high-risk patients portending worse outcomes. We hypothesized that ASA use can reduce distant metastases and improve outcomes in these patients. METHODS: Patients at our institutions from 2005 to 2018, with BC who did not achieve complete response (pCR) after NAC were reviewed (IRB protocol STU- 052012-019). Data, including evidence of ASA use, and clinico-pathologic parameters were analyzed. Survival outcomes were obtained (Kaplan Meier analysis) and univariate (UVA) and multivariable (MVA) Cox proportional hazards regression analyses were performed. RESULTS: 637 did not achieve pCR (ypN+ = 422). 138 were ASA users. Median follow-up for the control and ASA group were 3.8 (IQR 2.2-6.3) and 3.8 (IQR 2.5-6.4) years, respectively. Majority were stage II/III. 387 were hormone receptor positive, 191 HER2 +, and 157 triple negative. On UVA, ASA use, PR status, pathologic and clinical stage showed significance for DMFS, and disease-free survival (DFS). On MVA, ASA use associated with improved 5-year DFS (p = .01, 87.0% vs 79.6%, adjusted HR = 0.48) and improved 5-year DMFS (p = .04, 92.8% vs 89.2%, adjusted HR = 0.57). In the ypN + patients, ASA use associated with improved 5-year DMFS (p = .008, 85.7% vs 70.7%, adjusted HR = 0.43) and DFS (p = .02, 86.8% vs 74.3%, adjusted HR = 0.48). CONCLUSION: For non-responders, particularly ypN + patients, ASA use associated with improved outcome. These hypotheses-generating results suggest for development of prospective clinical trials of augmented ASA use in selected very high-risk BC patients.
Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/pathology , Neoadjuvant Therapy/methods , Prospective Studies , Chemotherapy, Adjuvant/methods , Disease-Free Survival , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Receptor, ErbB-2 , PrognosisABSTRACT
Background: There is currently no consensus among plastic surgeons regarding the optimal infection prophylaxis for immediate tissue expander placement following mastectomy. The goal of this study was to determine whether irrigation with 1 L of standard triple antibiotic solution (TAS) can achieve similar infection rates compared to a regimen of 180 mL of TAS with povidone-iodine solution (Betadine) painted on the field immediately prior to the placement of the expander. Methods: The 2 regimens were compared via retrospective propensity matching of all patients of the 2 senior authors who underwent bilateral tissue expander placement immediately following mastectomy with one of 3 mastectomy surgeons from January 2013 to December 2019 (n = 281). Groups were controlled for mastectomy surgeon, mastectomy type, mastectomy weight, age, race, body mass index, diabetes, hypertension, smoking, smoking status, prepectoral/subpectoral placement, use of acellular dermal matrix, operating room time, and duration of postoperative antibiotics. Results: Compared to the Betadine cohort (n = 65), the non-Betadine cohort (n = 65) experienced a similar rate of infections (13.8% vs 12.3%, P = 1.00), including major injections requiring intravenous antibiotic treatment (10.8% vs 9.2%, P = 1.00), after propensity matching. Infections in the non-Betadine cohort did not grow different bacteria on culture, require different antibiotic coverage, or result in prolonged duration of average antibiotic therapy (12.0 days vs 19.3 days, P = .19). Rates of subsequent expander washout and exchange (P = 1.00) and overall complications that required return to the operating room (P = .826) were similar between groups. Conclusion: The addition of Betadine solution to TAS added no benefit to infection prophylaxis or reduction of surgical complications in immediate tissue expander placement procedures.
Historique: Il n'y a pas de consensus entre les plasticiens au sujet de la prophylaxie optimale de l'infection lors de l'installation immédiate d'expanseurs tissulaires après une mastectomie. La présente étude visait à déterminer si l'irrigation à l'aide d'un litre de solution antibiotique triple (SAT) standard peut susciter un taux d'infection semblable à une posologie de 180 mL de SAT au moyen d'une solution de povidone-iode (BetadineMD) appliquée sur le champ opératoire immédiatement avant l'installation de l'expanseur. Méthodologie: Les chercheurs ont comparé les deux posologies par appariement rétrospectif des coefficients de propension de tous les patients des deux auteurs principaux, qui se sont fait installer des expanseurs tissulaires bilatéraux par l'un des trois chirurgiens ayant réalisé les mastectomies entre janvier 2013 et décembre 2019 (n=281). Les groupes ont été contrôlés en fonction du chirurgien ayant réalisé la mastectomie, du type et du poids de la mastectomie, de l'âge, de la race de l'indice de masse corporelle, du diabète, de l'hypertension, du tabagisme, du statut tabagique, de l'installation prépectorale ou subpectorale, du recours à une matrice dermique acellulaire, du temps passé en salle d'opération et de la durée de l'antibiothérapie postopératoire. Résultats: La cohorte qui n'avait pas pris de BetadineMD (n=65) a présenté un taux d'infection semblable à celle qui en avait pris (n=65; 12,3% par rapport à 13,8% p=1,00), y compris des injections majeures nécessitant une antibiothérapie par voie intraveineuse (9,2% par rapport à 10,8%, p=1,00) après l'appariement des coefficients de propension. Les infections dans la cohorte qui n'avait pas pris de BetadineMD n'ont pas révélé de bactéries différentes après la mise en culture, exigé une couverture antibiotique différente, ni entraîné une prolongation de la durée moyenne de l'antibiothérapie (12,0 jours par rapport à 19,3 jours, p=0,19). Le taux d'affaissement et d'échange subséquent des expanseurs (p =1,00) ainsi que le taux de complications globales qui ont entraîné un retour en salle d'opération (p = 0,826) étaient semblables entre les groupes. Conclusion: L'ajout d'une solution de BetadineMD à la SAT n'ajoutait rien à la prophylaxie de l'infection ni à la réduction des complications chirurgicales lors de l'installation immédiate d'expanseurs tissulaires.
ABSTRACT
PURPOSE: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and has a high propensity for distant metastases. Our previous data suggested that aspirin (acetylsalicylic acid, ASA) use may be associated with reduced risk of distant metastases in aggressive breast cancer; however, there are no reported studies on the potential benefit of ASA use in patients with IBC. METHODS: Data from patients with non-metastatic IBC treated between 2000-2017 at two institutions, were reviewed. Overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were performed using Kaplan-Meier analysis. Univariate and multivariable logistic regression models were used to identify significant associated factors. RESULTS: Of 59 patients meeting the criteria for analysis and available for review, 14 ASA users were identified. ASA users demonstrated increased OS (p = 0.03) and DMFS (p = 0.02), with 5-year OS and DMFS of 92% (p = 0.01) and 85% (p = 0.01) compared to 51% and 43%, respectively, for non-ASA users. In univariate analysis, pT stage, pN stage, and ASA use were significantly correlated (p < 0.05) with OS and DFS. On multivariable analysis, ASA use (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.01-0.8) and lymph node stage (HR, 5.9; 95% CI, 1.4-25.9) remained significant for OS and DFS ASA use (HR, 0.13; 95% CI, 0.03-0.56) and lymph node stage (HR, 5.6; 95% CI, 1.9-16.4). CONCLUSION: ASA use during remission was associated with significantly improved OS and DMFS in patients with IBC. These results suggest that ASA may provide survival benefits to patients with IBC. Prospective clinical trials of ASA use in patients with high-risk IBC in remission should be considered.
ABSTRACT
BACKGROUND: An extended interval between the two primary doses may reduce the risk of myocarditis/pericarditis after COVID-19 mRNA vaccination. Taiwan has implemented a two-dose regimen with a 12-week interval for adolescents. Here we present nationwide data of myocarditis/pericarditis following COVID-19 vaccinations. METHODS: Data on adverse events of myocarditis/pericarditis were from the Taiwan Vaccine Adverse Events Reporting System between March 22, 2021, and February 9, 2022. The reporting rates according to sex, age, and vaccine type were calculated. We investigated the rates among young individuals under different two-dose intervals and among those who received two doses of different vaccines. RESULTS: Among 204 cases who met the case definition of myocarditis/pericarditis, 75 cases occurred after the first dose and 129 after the second. The rate of myocarditis/pericarditis after COVID-19 vaccination varied across sex and age groups and was highest after the second dose in males aged 12-17 years (126.79 cases per million vaccinees) for the BNT162b2 vaccine and in males aged 18-24 years (93.84 cases per million vaccinees) for the mRNA-1273 vaccine. The data did not suggest an association between longer between-dose interval and lower rate of myocarditis/pericarditis among males and females aged 18-24 or 25-29 years who received two doses of the BNT162b2 or mRNA-1273 vaccine. Rates of myocarditis/pericarditis in males and females aged 18-49 years after receiving ChAdOx1-S - mRNA-1273 vaccination was significantly higher than after ChAdOx1-S - ChAdOx1-S vaccination. CONCLUSIONS: Myocarditis and pericarditis are rare following mRNA vaccination, with higher risk occurring in young males after the second dose.