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Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P < 0.001), Hispanic, Non-Hispanic Asian, Pacific Islander, or Black race (P < 0.001), non-partnered status (P < 0.001), and low median household income (P = 0.006). Primary tumor site, year of diagnosis, age, race, partnered status, and median household income correlated with the omission of systemic chemotherapy in GBM in adult patients.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/terapia , Glioblastoma/cirugía , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/epidemiología , Factores Socioeconómicos , Anciano de 80 o más Años , Disparidades en Atención de Salud , Programa de VERFRESUMEN
OBJECTIVES: From September 2022 an increase in Corynebacterium diphtheriae (C. diphtheriae) infections was reported in Europe. Our study focuses on 31 adolescent and young adult refugees with cutaneous C. diphtheriae infections detected in Germany. We examined treatment regimens and outcomes to provide targeted insights into the management of this infection. METHODS: We distributed a standardized survey, focused on children and adolescents presenting to paediatric clinics through the German Paediatric Infectious Diseases Society (DGPI) and additional professional contacts in Germany. Data were extracted from routine medical documentation and reported anonymously. RESULTS: A total of 31 individuals with cutaneous C. diphtheriae infection were reported by 9 centres. Two of these showed diphtheria toxin (DT) related systemic symptoms and four exhibited systemic inflammation requiring complex management. The remaining 25 cases, with exclusively cutaneous manifestations, were afebrile. Treatment with topical antiseptics and systemic antibiotics, mainly aminopenicillin/beta-lactamase inhibitors (BLI) (35%) or clindamycin (25%), achieved eradication in all but two cases treated with aminopenicillin/BLI. Treatment duration varied between 5 and 17 days. CONCLUSIONS: In refugees presenting with chronic skin wounds, C. diphtheriae should be included into the differential diagnosis. Fever seems to be a valuable marker to differentiate severe cases with potentially DT-mediated sequelae from exclusively cutaneous diphtheria (CD). For afebrile CD, topical antiseptics and oral antibiotic therapy with clindamycin for 7 days, followed by clinical surveillance appears to be a safe treatment regimen. Patients with CD who present with fever or pharyngitis should be thoroughly investigated including blood and pharyngeal swab cultures.
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Purpose: A mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process. Methods: Cardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process. Results: Cardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes. Conclusion: We are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.
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Macrófagos , Fagocitosis , Ratones , Animales , Inflamación/metabolismo , Interferones/metabolismo , Análisis de Secuencia de ARNRESUMEN
Purpose: The aim of this study was to explore how a multidisciplinary team (MDT) affects patterns of local or systematic treatment. Methods: We retrospectively reviewed the data of consecutive patients in the breast cancer with brain metastases (BCBM) database at our institution from January 2011 to April 2021. The patients were divided into an MDT group and a non-MDT group. Results: A total of 208 patients were analyzed, including 104 each in the MDT and non-MDT groups. After MDT, 56 patients (53.8%) were found to have intracranial "diagnosis upgrade". In the matched population, patients in the MDT group recorded a higher proportion of meningeal metastases (14.4% vs. 4.8%, p = 0.02), symptomatic tumor progression (11.5% vs. 5.8%, p = 0.04), and an increased number of occurrences of brain metastases (BM) progression (p < 0.05). Attending MDT was an independent factor associated with ≥2 courses of intracranial radiotherapy (RT) [odds ratio (OR) 5.4, 95% confidence interval (CI): 2.7-10.9, p < 0.001], novel RT technique use (7.0, 95% CI 3.5-14.0, p < 0.001), and prospective clinical research (OR 5.7, 95% CI 2.4-13.4, p < 0.001). Conclusion: Patients with complex conditions are often referred for MDT discussions. An MDT may improve the qualities of intracranial RT and systemic therapy, resulting in benefits of overall survival for BC patients after BM. This encourages the idea that treatment recommendations for patients with BMBC should be discussed within an MDT.
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BACKGROUND AND OBJECTIVES: Neoadjuvant chemotherapy (nCT) appears in a few clinical studies as an alternative to neoadjuvant chemoradiation (nCRT) in selected patients with locally advanced rectal cancer (LARC). We aimed to compare the clinical outcomes of nCT with or without nCRT in patients with LARC and to identify patients who may be suitable for nCT alone. MATERIALS AND METHODS: A total of 155 patients with LARC who received neoadjuvant treatment (NT) were retrospectively analysed from January 2016 to June 2021. The patients were divided into two groups: nCRT (n = 101) and nCT (n = 54). More patients with locally advanced disease (cT4, cN+ and magnetic resonance imaging-detected mesorectal fascia [mrMRF] positive [+]) were found in the nCRT group. Patients in the nCRT group received a dose of 50 Gy/25 Fx irradiation with concurrent capecitabine, and the median number of nCT cycles was two. In the nCT group, the median number of cycles was four. RESULTS: The median follow-up duration was 30 months. The pathologic complete response (pCR) rate in the nCRT group was significantly higher than that in the nCT group (17.5% vs. 5.6%, p = 0.047). A significant difference was observed in the locoregional recurrence rate (LRR); 6.9% in the nCRT group and 16.7% in the nCT group (p = 0.011). Among patients with initial mrMRF (+) status, the LRR in the nCRT group was significantly lower than that in the nCT group (6.1% vs. 20%, p = 0.007), but not in patients with initial mrMRF negative (-) (10.5% in each group, p = 0.647). Compared with the nCT group, a lower LRR was observed in patients in the nCRT group with initial mrMRF (+) converted to mrMRF (-) after NT (5.3% vs. 23%, p = 0.009). No significant difference was observed between the two groups regarding acute toxicity and overall and progression-free survivals. Multivariate analysis showed that nCRT and ypN stage were independent prognostic factors for the development of LRR. CONCLUSION: Patients with initial mrMRF (-) may be suitable for nCT alone. However, patients with initial mrMRF (+) converted to mrMRF (-) after nCT are still at high risk of LRR, and radiotherapy is recommended. Prospective studies are required to confirm these findings.
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Terapia Neoadyuvante , Selección de Paciente , Neoplasias del Recto , Terapia Neoadyuvante/efectos adversos , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/terapia , Estudios Retrospectivos , Imagen por Resonancia Magnética , Supervivencia sin Progresión , Pronóstico , Humanos , Masculino , Adulto , Persona de Mediana Edad , Anciano , Leucopenia/etiología , Radiodermatitis/etiologíaRESUMEN
In vitro experiments have shown that the E2 protein of human papillomaviruses (HPV) binds to the upstream regulatory region (URR) of the viral genome and modulates transcription. Additionally, it seems to be a necessary component for viral DNA replication together with E1. We have developed a transgenic mouse model containing the URR region of the low-risk virus HPV11 that regulates the expression of the lacZ reporter gene. Most interestingly, in these mice, the transgene was exclusively expressed in the bulge region of the hair follicle but not in any other tissues. Further experimental data indicate that in double transgenic mice that also express the HPV11-E2 protein under the control of the Ubiquitin C-promoter, the transcription of the reporter gene is modulated. When E2 is present, the expression of the reporter gene also occurs exclusively in the bulge region of the hair follicles as it does in the single transgenic mice, but the expression of the lacZ driven by the URR is increased and the statistical spread is greater. Even if the expression of the reporter gene occurs in the hair follicles of the dorsal skin of an animal uniform, E2 obviously has the capacity for both to induce and to repress the URR activity in vivo.
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Replicación del ADN , Replicación Viral , Ratones , Animales , Humanos , ADN Viral/metabolismo , Regiones Promotoras Genéticas , Ratones TransgénicosRESUMEN
INTRODUCTION: Short course regimen has become the major trend in the field of adjuvant radiotherapy for patients with breast cancer. Hypofractionated radiotherapy (HF-RT) regimen of 40-42.5 Gy in 15-16 fractions has been established as a preferred option for whole breast irradiation. However, few evidences of hypofractionated regional nodal irradiation (RNI), especially involving internal mammary nodes (IMNs), could be available during the era of intensity-modulated radiation therapy (IMRT). Against this background, we design this trial to explore the hypothesis that HF-RT regimen involving RNI (including infraclavicular, supraclavicular nodes and IMNs) will be non-inferior to a standard schedule by using IMRT technique. METHODS AND ANALYSIS: This is an open-label randomised, non-inferior, multicentre phase III trial. Patients with breast cancer with an indication for RNI after breast conserving surgery or mastectomy are randomised at a ratio of 1:1 into the following two groups: hypofractionated regimen of 2.67 Gy for 16 fractions or conventional regimen of 2 Gy for 25 fractions. The dose was prescribed to ipsilateral chest wall or whole breast and RNI (including infraclavicular, supraclavicular nodes and IMNs, lower axilla if indicated). The trial plans to enrol a total of 801 patients and all patients will be treated using IMRT technique. The primary endpoint is 5-year locoregional recurrence. The secondary endpoints include 5-year distant metastasis free survival, invasive recurrence-free survival, overall survival, accumulative acute radiation-induced toxicity and accumulative late radiation-induced toxicity, cosmetic outcomes and quality of life. ETHICS AND DISSEMINATION: The study has been approved by the Ethical Committee of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine (version 2018-95-3) and approvals from ethical committee of each participating centre have also been obtained. Research findings will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03829553.
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Neoplasias de la Mama , Traumatismos por Radiación , Radioterapia de Intensidad Modulada , Humanos , Femenino , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mastectomía , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Calidad de Vida , Recurrencia Local de Neoplasia/patología , China , Traumatismos por Radiación/etiología , Adyuvantes Inmunológicos , Radioterapia Adyuvante , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como AsuntoRESUMEN
Background: Many studies have shown that the peripheral blood inflammatory index and nutritional index, such as the platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), lymphocyte monocyte ratio (LMR), systemic inflammation response index (SIRI), pan-immune-inflammation value (PIV), systemic immune-inflammation index (SII), and prognostic nutrition index (PNI), are independent prognostic factors for tumors. The present study aimed to investigate the prognostic role of these peripheral blood indexes before treatment in locally advanced gastric cancer (LAGC) treated with adjuvant chemoradiotherapy after D2 dissection. Methods: A total of 89 patients with LAGC who underwent D2 gastrectomy and adjuvant chemoradiotherapy at our hospital from 2010-2018 were eligible. Systemic inflammatory indicators before treatment were evaluated. Receiver operating characteristic curve (ROC), Kaplan-Meier analysis, and Cox regression were utilized for prognosis evaluation. Results: The median follow-up time was 29.1 (4.1-115.8) months. The overall survival at 3 years (OS) and the disease-free survival (DFS) were 78.9% and 59.1%, respectively. According to the ROC curve for 3-year DFS, the best cut-off values of pre-treatment NLR, PLR, LMR, SII, SIRI, PIV and PNI were 1.7, 109.3, 2.9, 369.2, 0.58, 218.7, and 48, respectively. Multivariate Cox regression analysis showed that NLR was an independent prognostic factor for DFS (HR 2.991, 95%CI 1.085-8.248, P = 0.034). Kaplan-Meier analysis showed that a higher NLR (>1.70) was significantly associated with a poorer OS (3-year OS: 68.8% vs 92.9%, P = 0.045) and DFS (3-year DFS: 47.5% vs 80.9%, P = 0.005). In terms of the free locoregional recurrence rate (LRR), the prognosis of patients with high NLR was also significantly worse than those with low NLR (70.2% vs 96.0%, P = 0.017). Paraaortic lymph nodes were the most common site of LRR (7/14 patients). The seven cases of paraaortic lymph node metastasis occurred in patients with high NLR. Conclusions: In our retrospective analysis, we found that pretreatment NLR could serve as a prognostic factor for survival in LAGC treated with adjuvant chemoradiotherapy after D2 dissection, especially for the prediction of LRR and paraaortic lymph node metastasis. Prospective studies are needed to confirm our findings.
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Purpose: We sought to explore the role of nomogram-combined biomarkers, mammographic microcalcification and inflammatory hematologic markers in guiding local therapy decisions in ductal carcinoma in situ (DCIS) subgroups with different ipsilateral breast tumour recurrence (IBTR) risk. Methods: Between January 2009 and December 2018, consecutive patients with DCIS and breast conserving surgery (BCS) were enrolled and randomly assigned to a training cohort (n = 181) and internally validation cohort (n = 78). Multivariate analyses were performed to identify predictors of IBTR. Model performance was evaluated by the concordance index (C-index) and calibration plot. The time-to-event curves were calculated by the Kaplan−Meier methods and compared by the log-rank test. Results: In total, 259 patients were enrolled and 182 of them received whole breast irradiation (WBI). After a median follow-up of 51.02 months, 23 IBTR events occurred in the whole cohort. By multivariate analyses of training cohort, presence of microinvasion, Ki67 index >14%, mammographic-clustered fine linear microcalcifications and neutrophil/lymphocyte ratio before BCS (preop-NLR), >1.1 remained independent risk factors of IBTR to develop a nomogram. The C-indexes of the nomogram were 0.87 and 0.86 in the training and internal validation set, respectively. Calibration plots illustrated good agreement between the predictions and actual observations for 5-year IBTR. Cut-off values of nomogram point were identified as 53 and 115 points, which divided all patients into low-, intermediate- and high-risk groups. Significant differences in IBTR existed between low-, intermediate- and high-risk subgroups (p < 0.01). For the whole cohort and ER-positive tumours, the benefit of WBI was found only in the intermediate-risk subgroup, but not in those with low or high risk. Fourteen out of 23 IBTRs occurred outside the original quadrant and all occurred in the high-risk group. Conclusions: The novel nomogram demonstrated potential to separate the risk of IBTR and locations of IBTR. For the whole cohort and ER-positive tumours, the benefit of WBI was restricted to an intermediate-risk subgroup.
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Purpose: To determine the relationship between time to radiotherapy (TTR) and survival outcomes in breast cancer (BC) patients treated with neoadjuvant treatments (NATs). Methods: Continuous non-metastatic BC patients receiving NAT and adjuvant radiotherapy (RT) from 2009 to 2016 were retrospectively reviewed. A multivariable Cox model with restricted cubic splines (RCSs) was used to determine the panoramic relationship between TTR and survival outcomes. Multivariable analysis was used to control for confounding factors between the groups of TTR. Results: A total of 315 patients were included. The RCS modeling demonstrated a non-linear relationship between TTR and survival outcomes. The lowest risk for distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) was observed at the TTR of 12 weeks, and the lowest risk of BC-specific survival (BCSS) at 10 weeks. TTR was accordingly transformed into categorical variables as ≤10, 11-20, and >20 weeks. Multivariable analysis revealed that the TTR of ≤10 weeks was an independent prognostic factor for worse DMFS (HR = 2.294, 95% CI 1.079-4.881) and RFS (HR = 2.126, 95% CI 1.038-4.356) compared with the TTR of 10-20 weeks, while the is no difference in DMFS, RFS, and BCSS between TTR >20 weeks and TTR of 10-20 weeks. Conclusion: There exists a non-linear relationship between TTR after surgery and survival outcomes in patients treated with NAT. Early initiation of RT following surgery does not seem to be associated with a better therapeutic outcome. A relatively flexible recommendation of TTR could be adopted in clinical practice.
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Purpose: The effect of adjuvant irradiation after mastectomy in early-stage breast cancer patients remains controversial. The present study aims to explore the clinical benefit obtained from adjuvant radiotherapy among post-mastectomy pT1-2N1 breast cancer patients who received adjuvant modern systemic therapy. Methods: Medical records of consecutive patients with pT1-2N1 breast cancer who received mastectomy in our institution between January 2009 and December 2016 were retrospectively reviewed. High-risk features consist of patient age, number of positive lymph nodes, T stage, and Ki67 index, which were developed previously at our institution using early-stage breast cancer patients after mastectomy without adjuvant radiotherapy. Differences of survival and local recurrence were compared between no-postmastectomy radiotherapy (PMRT) and PMRT group according to number of risk factors. The time-to-event curves were calculated by the Kaplan-Meier methods and compared by the log-rank test. Propensity score matching (PSM) was performed to reduce the imbalances in patient characteristics. Results: A total of 548 patients were enrolled (no-PMRT: 259 and PMRT: 289). After a median follow-up of 69 months, the 5-year rate of DFS, BCSS, and LRR in the overall cohort was 90.2%, 97.4%, and 3.6%, respectively. PMRT did not significantly improve DFS, BCSS, and LRRFS in the whole cohort. Patients were divided into low-risk (with no or one risk factor) and high-risk (with two or more risk factors) groups. According to the univariable and multivariable analysis, high-risk group (HR = 1.81, 95% CI 1.11-2.98, p = 0.02) was demonstrated as an independent risk factor for DFS. For the high-risk group, PMRT significantly improved DFS from 81.4% to 91.9% and BCSS from 95.5% to 98.6% and decreased the 5-year rate of LRR from 5.6% to 1.4%, respectively (p < 0.01, p = 0.05, and p = 0.06). However, no survival benefit from PMRT was observed in the low-risk group in terms of DFS, BCSS, and LRR (p = 0.45, p = 0.51, and p = 0.99, respectively). In multivariate analysis, PMRT remained an independent prognostic factor for DFS (HR = 0.50, 95% CI 0.24-1.00, p = 0.05) in the high-risk group. After PSM analysis, the survival benefit of PMRT was sustained in high-risk patients. Conclusion: PMRT significantly improved DFS in high-risk pT1-2N1 breast cancer patients, but not in low-risk patients. Independent validation of our scoring system is recommended.
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OBJECTIVE: The outbreak of COVID-19 pandemic has greatly impacted on radiotherapy (RT) strategy for breast cancer patients, which might lead to increased distressing psychological symptoms. We performed a multi-center cross-section survey to investigate prevalence of fear of cancer recurrence (FCR) and predictors for FCR in patients referred to RT during pandemic. METHODS: 542 patients were consecutively enrolled from three regions in China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients' characteristics were collected using an information sheet, Fear of progression questionnaire-short form, Hospital Anxiety/Depression Scale and EORTC QLQ-C30. The hierarchical multiple regression models were performed. RESULTS: 488 patients with complete data were eligible. The RT strategy was affected in 265 (54.3%) patients, including 143 with delayed RT initiation, 66 believing to have delayed RT initiation but actually not, 24 with RT interruptions, 19 shifting to local hospitals for RT and the remaining 13 influenced on both RT schedule and hospital level. The model explained 59.7% of observed variances in FCR (p<0.001) and showed that influence of RT strategy had significantly impacted on FCR (â³R2 = 0.01, â³F=2.966, p=0.019). Hospitals in Shanxi province (ß=-0.117, p=0.001), emotional function (ß=-0.19, p<0.001), social function (ß=-0.111, p=0.006), anxiety (ß=0.434, p<0.001) and RT interruption (ß=0.071, p=0.035) were independent predictors. CONCLUSIONS: RT strategy for breast cancer patients was greatly influenced during pandemic. RT interruption is an independent predictor for high FCR. Our findings emphasize the necessity to ensure continuum of RT, and efforts should be taken to alleviate FCR through psychological interventions.
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Radiation-induced heart disease (RIHD) leads to myocardial dysfunction and metabolic abnormalities in patients treated with thoracic irradiation which restricts the long-term survival benefits of radiotherapy. There is no specific or effective manner of intervention currently available. Asparaginyl endopeptidase (AEP) plays a pivotal role in the maintenance of cellular functions through regulating proteolytic cleavage as peptidase enzyme. We aimed to investigate the role of unique cardiac AEP in cardiac function by modulating key signaling elements in the myocardium. The murine heart was exposed to a single dose of 14 Gy radiation. Cellular signaling and apoptosis was analyzed in human and rat cardiomyocytes treated with various doses of radiation, we observed expression of AEP was increased by immunohistochemical staining in murine heart exposed to radiation. The AEP production along with its increased level of mRNA expression was associated with increased doses of radiation (0, 2, 5, 10 Gy) in cardiomyocytes. The myocardial cells transfected with AEP overexpression showed overall cellular viability enhancement, DNA damage inhibition, the foci formation of γ-H2AX suppressed and DNA repair enhancement significantly after radiation exposure. Small interfering RNA-mediated AEP knockdown was with reduced cardiomyocyte viability, elevated apoptotic rate, increased γ-H2AX foci formation and inhibited DNA repair as well after irradiation. After radiation exposure of 10 Gy, the expression of AEP increased in P53 overexpressing cardiomyocytes and decreased in the P53 knockdown cells, indicates that radiation-induced expression of AEP might be regulated by P53. Moreover, treatments with either AEP overexpression or knockdown showed enhanced NRF2 activity in the nuclear or suppressed NRF2 expression in the cytoplasm of myocardial cells after irradiation, respectively, defined a possible regulatory effect of AEP associated with diminished NRF2 translocation and activation by radiation exposure, including impair myocardium and myocardial apoptosis. These findings suggest that increased levels of AEP in failing myocardium after irradiation is mediated by P53 and regulate a novel pathway that involves NRF2 activation. AEP is essential for maintaining cellular redox homeostasis of cardiac function.
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BACKGROUND: One of the most controversial areas in gastrointestinal oncology is the benefit of postoperative chemoradiotherapy (CRT) over chemotherapy (CT) alone after D2 dissection of locally advanced gastric cancer (LAGC). We aimed to identify the LAGC patients who may benefit from adjuvant CRT. METHODS: We analyzed retrospectively 188 patients receiving radical gastrectomy with D2 dissection for LAGC in our hospital. Patients were divided into two balanced groups by using propensity score matching: CRT group (n = 94) received adjuvant CRT, and CT group received adjuvant CT alone. RESULTS: At a median follow-up of 27.10 months, 188 patients developed 79 first recurrence events (36 in CRT group and 43 in CT group). Our results showed that adjuvant CRT significantly decreased the risk of developing local regional recurrence (LRR) when compared to CT alone (14.9% vs. 25.5%, p = 0.044), while the estimated 3-year disease-free survival (DFS) was comparable between the CRT and CT groups (59.3% vs. 50.9%, p = 0.239). In the subgroup analysis, a significantly decreased LRR rate was also observed in LAGC patients with N1-3a stage after adjuvant CRT (p = 0.046), but not for N3b. Para-aortic lymph nodes (station No. 16) were the most frequent sites of LRR. After receiving radiotherapy, recurrence of 16 a2 region and 16 b1 region were significantly deceased (p = 0.026 and p = 0.044, respectively). Patients who received irradiation more than 4 months after surgery showed an increased risk of LRR (p = 0.022). CONCLUSIONS: This study showed that adjuvant CRT significantly reduced LRR after D2 dissection of LAGC. Early initiation of adjuvant RT with clinical target volume encompassing a2 and b1 regions of para-aortic lymph nodes is recommended for pN1-3a patients after D2 dissection.
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This study aims to identify the density of TILs in ductal carcinoma in situ (DCIS) in terms of prognostic significance with recurrence and the benefit of whole breast irradiation (WBI). The clinicopathological data of DCIS patients from Jan 2009 to Dec 2016 who received breast-conserving surgery (BCS) were retrospectively reviewed. Cox regression analysis was used to confirm independent prognostic factors of ipsilateral breast tumor recurrence (IBTR). Kaplan-Meier method was utilized to analyze IBTR and values of WBI. Touching-tumor-infiltrating lymphocytes (TILs) were defined by TILs touching or within one lymphocyte cell thickness from the malignant ducts' basement membrane. In total, 129 patients were enrolled in this analysis with 98 patients who received WBI. After a median follow-up of 53.0 months, there were 16 IBTR events with five invasive IBTRs. Univariate and multivariate analyses showed that touching-TILs >5 were an independent prognostic factor for higher IBTR (HR = 6.17, 95%CI 1.95-19.56, p < .01). The whole cohort was classified into two subgroups: dense group (>5 touching-TILs per duct) and sparse group (≤5 touching-TILs per duct). Dense touching-TILs were associated with unfavorable biologic characteristics. The 5-y rate of IBTR between dense and sparse group was 29.0% versus 4.5% (p < .01). For the sparse group, WBI significantly reduced the rate of 5-y-IBTR risk from 13.2% to 1.7% (p = .02), but there was no benefit of WBI in the dense group. Touching-TILs density was heterogeneous in patients with DCIS. Sparse touching-TILs were associated with better prognosis and benefit from WBI. Dense touching-TILs not only were associated with a higher risk of IBTR but also lack of benefit from WBI.
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Carcinoma Intraductal no Infiltrante , Carcinoma Intraductal no Infiltrante/cirugía , Humanos , Linfocitos Infiltrantes de Tumor , Recurrencia Local de Neoplasia , Pronóstico , Estudios RetrospectivosRESUMEN
PURPOSE: The aim of this study was to evaluate the impact of time to radiotherapy (TTR) after completion of chemotherapy (CT), and TTR after surgery, in breast cancer (BC) patients. PATIENTS AND METHODS: Continuous breast cancer patients treated with surgery and CT followed by radiotherapy (RT) from 2009 through 2015 were retrospectively reviewed. Patients were categorized into four groups with respect to TTR after CT, i.e. <4, 4-8, 8-12, and >12 weeks, and TTR after surgery, i.e. <147, 147-180, 180-202, and >202 days. The Cox proportional hazards model was used to identify the independent effect of TTRs. RESULTS: Overall, 989 patients were enrolled. Patients with a TTR of >12 weeks after CT showed significantly worse breast cancer-specific survival (BCSS) and overall survival (OS) compared with those who had a TTR of <4 weeks (BCSS: hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.1-0.76; OS: HR 0.33, 95% CI 0.13-0.88), 4-8 weeks (BCSS: HR 0.23, 95% CI 0.08-0.66; OS: HR 0.29, 95% CI 0.11-0.8), and 8-12 weeks (BCSS: HR 0.22, 95% CI 0.05-0.96; OS: HR 0.23, 95% CI 0.06-0.99). TTR after surgery showed no significant association with survival outcomes in the entire cohort, except in patients with hormone receptor (HR)-positive disease and those receiving mastectomy. In HR-positive tumors, a TTR after CT of >12 weeks remained an independent predictor for adverse BCSS and OS. CONCLUSION: Initiation of RT beyond 12 weeks after CT might compromise survival outcomes. Efforts should be made to avoid delaying RT, especially after completion of CT and in patients with HR-positive tumors, positive lymph nodes, and those receiving mastectomy.
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Neoplasias de la Mama , Mama , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Humanos , Mastectomía , Radioterapia Adyuvante , Estudios RetrospectivosRESUMEN
The ability of electrospun polyvinylidene fluoride (PVDF) fibers to produce piezoelectricity has been demonstrated for a while. Widespread applications of electrospun PVDF as an energy conversion material, however, have not materialized due to the random arrangement of fibers fabricated by traditional electrospinning. In this work, a developed 3D electrospinning technique is utilized to fabricate a PVDF micro wall made up of densely stacked fibers in a fiber-by-fiber manner. Results from X-ray diffraction (XRD) and Fourier transform infrared spectra (FTIR) demonstrate that the crystalline structure of this PVDF wall is predominant in the ß phase, revealing the advanced integration capability of structural fabrication and piezoelectric poling with this 3D electrospinning. The piezoelectric response along the radial direction of these PVDF fibers is measured while the toppled micro wall, comprised of 60 fibers, is sandwich assembled with a pair of top/bottom electrodes. The measured electrical output is ca. 0.48 V and 2.7 nA. Moreover, after constant mechanical compression happening over 10,000 times, no obvious reduction in the piezoelectric response has been observed. The combined merits of high-precision 3D fabrication, in situ piezoelectric poling, and high mechanical robust make this novel structure an attractive candidate for applications in piezoelectric energy harvesting and sensing.
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BACKGROUND: Lacking quantitative evaluations of clinicopathological features and the risk factors for loco-regional recurrence (LRR) in gastric cancer after D2 gastrectomy, we aimed to develop a competing risk nomogram to identify the risk predictors for initial LRR. METHODS: We retrospectively analysed 1105 patients who underwent radical gastrectomy with D2 resection for stage I-III gastric cancer. A nomogram predicting initial LRR of gastric cancer was conducted based on Fine and Grey's competing risk analysis. The predictive accuracy and discriminative ability of the model were determined using the concordance index (C-index) and calibration curve. Decision tree analysis was performed for patient grouping. RESULTS: At a median follow-up of 28.4 months, 274 patients developed 373 first recurrence events (local, regional, and distant disease). The median recurrence-free survival (RFS) was 16.7 months. Multivariate competing risk analysis showed that age (SHR, 1.72; 95% CI, 1.10-2.83, p = 0.031), CEA (SHR, 1.94; 95% CI, 1.09-3.46, p = 0.024), pT4 (SHR, 2.77; 95% CI, 1.01-7.57, p = 0.047), lymph node metastasis (SHR 1.92, 95% CI: 1.09-3.38, p = 0.024) and LVI (SHR, 1.84; 95% CI, 1.06-3.20, p = 0.028) were independent risk factors for LRR (all p < 0.05). The nomogram incorporating these factors achieved good agreement between prediction and actual observation with a concordance index of 0.738 (95% CI, 0.767 to 0.709). In a subgroup analysis of node-positive patients, pN3b was associated with increased peritoneal and distant metastasis (p = 0.048). The para-aortic lymph nodes were the most frequent sites (n = 71) of LRR, and among them, the 16a2 and 16b1 nodes exhibited even more prevalence (90.1 and 81.7%). CONCLUSIONS: Adjuvant radiotherapy might be recommended in gastric cancer patients ≥65 years old or those with pN+, pT4, LVI, or increased CEA levels, particularly in high-risk or pN1-3a patients. The competing risk nomograms may be considered as convenient and individualized predictive tools for LRR in gastric cancer after D2 gastrectomy. It is also recommended that the clinical target volume (CTV) include 16a2 and 16b1 regions of para-aortic lymph nodes.
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Adenocarcinoma/cirugía , Gastrectomía/efectos adversos , Recurrencia Local de Neoplasia/diagnóstico , Nomogramas , Medición de Riesgo/métodos , Neoplasias Gástricas/cirugía , Adenocarcinoma/patología , Adulto , Anciano , Anciano de 80 o más Años , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Recurrencia Local de Neoplasia/etiología , Pronóstico , Estudios Retrospectivos , Neoplasias Gástricas/patología , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: The role of regional nodal irradiation (RNI) in patients with cN1 breast cancer following neoadjuvant treatment (NAT) is still controversial. The Neo-Bioscore staging system has shown promising prospect in assessing individual prognosis after NAT, and we sought to evaluate the role of Neo-Bioscore in guiding RNI following NAT. METHODS: Medical records of 163 women with cN1 and ypN0-1 disease treated with NAT between 2009 and 2014 were retrospectively reviewed and a Neo-Bioscore was assigned to each patient. Survivals were calculated using the Kaplan-Meier method and compared with the log-rank test. Multivariate analysis was used to identify independent predictors by using Cox proportional hazards models. RESULTS: The median follow-up after surgery was 59.4 months. Of all 163 patients, 119 received RNI. At surgery, 36 patients (22.1%) had pathological complete response (pCR), while 89 patients (54.6%) achieved ypN0. In the whole cohort, RNI significantly improved distant metastasis-free survival (DMFS) on multivariable analysis. In the subgroup of patients with a Neo-Bioscore of 1-3, RNI significantly improved the 5-year DMFS rate of 97.0% versus 76.9% (p = 0.002), 5-year regional node recurrence-free survival rate of 95.5% versus 76.9% (p = 0.007), and 5-year overall survival rate of 100% versus 89.2% (p = 0.005). No significant difference in outcomes was found between the RNI and non-RNI groups in patients with a score of 4-6. CONCLUSIONS: In patients with cN1 and ypN0-1, RNI was found to significantly improve DMFS following NAT. Patients with a Neo-Bioscore of 1-3 are more likely to benefit from RNI, however a large prospective study is needed to confirm this finding.
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Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Carcinoma Lobular/patología , Ganglios Linfáticos/patología , Terapia Neoadyuvante/mortalidad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias/normas , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/radioterapia , Carcinoma Lobular/terapia , Femenino , Estudios de Seguimiento , Humanos , Ganglios Linfáticos/efectos de la radiación , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/terapia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Radiotherapy (RT) is a modality of salvage therapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but its efficacy is currently not well defined. This paper reports a retrospective review of patients who received salvage RT for R/R DLBCL in our hospital. METHODS: We selected 32 patients who had relapsed and had progressive disease after chemotherapy or partial remission (PR) after chemotherapy. The patients had a median age of 47 years (range, 13-85 years) and were treated between January 1, 2009, and June 30, 2016. The histological type was DLBCL in all cases. Progression-free survival (PFS) and overall survival (OS) were estimated with the Kaplan-Meier method; predictors for adverse factors were evaluated using a Cox proportional hazards regression model. RESULTS: Median age-adjusted International Prognostic Index (IPI) score was 3 (range, 0-4), and 20 (62.5%) patients had large tumors. Patients were irradiated with a median dose of 42.7 Gy (range, 30-54 Gy): 4 (12.5%) by conventional RT, 2 (6.3%) by conformal 3D technique and 26 (81.3%) by intensity-modulated RT (IMRT). Most toxicities were mild (CTCAE grade 1 or 2), including neutropenia, diarrhea, dermatitis, mucositis and dysphagia. With a median follow-up of 25.4 months (range, 0.4-98.9 months) after irradiation, the 5-year PFS and OS were 61.8% and 83.2%, respectively. In multivariate analysis, adverse factors associated with PFS in our cohort were multiple lesions. CONCLUSIONS: Due to its low toxicity and ease of use, RT should remain a salvage therapy option for patients with R/R DLBCL.