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Roberts, C. J., delivered the opinion of the Court, in which Kennedy, Ginsburg, Breyer, Sotomayor, and Kagan, JJ., joined. Scalia, J., filed an opinion concurring in the judgment, in which Thomas, J., joined, and in which Alito, J., joined as to Part I. Thomas, J., filed an opinion concurring in the judgment, in which Scalia, J., joined, and in which Alito, J., joined as to Parts I, II, and III. Alito, J., filed an opinion concurring in the judgment.
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Previous studies have shown that preoperative anemia is correlated with the prognoses of various solid tumors. This study was performed to determine the effect of preoperative anemia on relapse and survival in patients with breast cancer.
In this study, we aimed to determine the effects of preoperative anemia on relapse (local relapse, lymph node metastasis, distant metastasis, and overall relapse) and survival (local relapse-free survival, lymph node metastasis-free survival, distant metastasis-free survival, relapse-free survival, and overall survival) in patients undergoing breast cancer surgery.
A total of 2960 patients with breast cancer who underwent surgery between 2002 and 2008 at the Sun Yat-sen University Cancer Center (Guangzhou, PR China) were evaluated in a retrospective analysis. This study was approved by the ethics committee of the Sun Yat-sen University Cancer Center. No consent from patients was needed.
We defined local relapse-free survival (LRFS) as the duration from the surgery date to the date when local relapse was diagnosed. Lymph node metastasis-free survival (LNMFS) was defined as the duration from the surgery date to the date when lymph node metastasis was diagnosed. Distant metastasis-free survival (DMFS) was defined as the duration from the surgery date to the date when distant metastasis was diagnosed. Relapse-free survival (RFS) was defined as the duration from the surgery date to the date when any relapse was diagnosed and overall survival (OS) as the duration from the surgery date to the date of death or the last follow-up.
The relation between Hb levels and various risk factors was examined by Spearman rank correlation coefficients. As shown in Table 2, we found that there was a significant positive correlation between Hb levels and BMI, and a negative correlation with T- and N-status and clinical stages.
Preoperative anemia has been reported to be associated with poor prognosis in many types of tumors [6, 14]. In our present study, a low preoperative Hb level was shown to be associated with local and distant relapses in breast cancer patients. Shorter survival was also observed in anemic patients. To the best of our knowledge, our study was the first to discover that preoperative Hb levels were associated with tumor (T) and nodal (N) status of breast cancer and BMI. Further, the most important study finding was that preoperative anemia was shown to be an independently prognostic factor for LRFS, LNMFS, DMFS, RFS, and OS in breast cancer patients, even in the same clinical stage or at lower stages.
Causes of anemia in cancer patients are multifactorial and can be considered as results of cancer invasion, induced by treatment (after radiotherapy or chemotherapy), or chronic kidney disease [15]. Among the three factors mentioned above, the first one is the largest contributor. Cancer itself can cause or exacerbate anemia in several ways [16]. Cancer cells may suppress hematopoiesis via bone marrow infiltration directly. They also generate cytokines that lead to functional iron deficiency, which decreases the production and shorten the survival of red blood cells [17]. Also, chronic blood loss at tumor sites through cancer cells infiltration can exacerbate anemia. Other indirect effects include nutritional deficiencies of iron, folate, and vitamin B12 secondary to anorexia or hemolysis by immune-mediated antibodies. For the factors mentioned above, it is plausible that preoperative anemia is more frequent in higher clinical stages and low BMI in association with malnutrition.
Many studies supported that pre-treatment Hb levels during adjuvant or neoadjuvant chemotherapy were related to the prognosis of breast cancer. However, few studies focused on the preoperative Hb levels [12, 18, 19]. Kandemir et al. reported that preoperative anemia was an independent risk factor of disease-free survival and overall survival in 336 early-stage breast cancer patients [11]. Our results not only supported their conclusion but also showed that preoperative anemia was associated with local relapse-free survival, lymph node metastasis-free survival, and distant metastasis-free survival in a larger cohort.
Although hypoxia may be a reasonable explanation for the association between anemia and survival of breast cancer, there was no direct evidence of hypoxia in cancer cells in our large population study. Emerging new tools that can measure the local Hb level and O2 tension directly in tumor tissues may solve this problem in the future. Our study provided a clue for further investigations to clarify the complex mechanisms of hypoxia in breast cancer.
Since preoperative anemia was associated with poor prognosis in breast cancer patients in our study, would patients benefit from anemia treatment preoperatively? Or could we improve the prognosis after administering treatment for anemia? The answer to this question is somewhat ambiguous because of the complexity of anemia. For most of patients with breast cancer without chemotherapy, preoperative anemia was caused by multiple etiologies, including blood loss, functional iron deficiency, erythropoietin deficiency secondary to renal disease, tumoral marrow involvement, well as other factors. Evaluation of anemia should be performed carefully before treatment because an unsuitable treatment might lead to adverse effects. The most common treatment options for anemic patients include iron therapy, red cell transfusion, and erythropoietic-stimulating agents. For iron therapy, nutritional status (iron, total iron binding capacity, ferritin, transferrin saturation, folate, and vitamin B12) and renal function should be evaluated. Only absolute iron deficiency will benefit from intravenous or oral iron monotherapy [38, 39]. Unfortunately the absence of data regarding the nutritional status and renal function of our patients impeded further analysis.
Red cell transfusion is an acceptable treatment option for anemic breast cancer patients, especially for those requiring rapid improvement of Hb levels. However, large-scale studies involving cancer patients found that red cell transfusion was associated with increased thrombosis risk as well as increased mortality risk [40]. Additionally, mild anemia accounted for 99% anemic patients in this study; thus, transfusions might not be necessary. As for erythropoietic-stimulating agent therapy, it was suitable only for patients receiving palliative, myelosuppressive chemotherapy with a Hb
YJ Zhang carried out the design and drafted the manuscript. YY Chen performed the interpretation of the data and statistical analysis. DT Chen, Y Jiang, W Huang, HD Ouyang and W Xing participated in acquisition of data. MS Zeng and XM Xie participated in the critical revision of the manuscript for important intellectual content. WA Zeng carried out the major design and funding support, and performed supervision and coordination with other departments. All authors read and approved the final manuscript.
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
The irony is that any charge that has been expunged by a court is probably of such age and of such a minor nature that even if the applicant listed it, as required on the SF-86, it would not serve as a barrier to obtaining a security clearance. But, for whatever reason, I see a number of smart people every year suddenly develop poor reading comprehension skills with respect to the criminal record section of the SF-86 or blame advice from their criminal defense attorney.
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Dzhokhar "Jahar" Anzorovich Tsarnaev (born July 22, 1993)[note 1] is a Kyrgyz-American terrorist of Chechen descent.[4][5] Tsarnaev was convicted of perpetrating the Boston Marathon bombing by planting pressure cooker bombs near the finish line of the race on April 15, 2013, along with his older brother Tamerlan Tsarnaev.[6][7][8][9] The bombings killed three people and injured 281 others.[10]
Tsarnaev and his family had traveled to the United States on a tourist visa and subsequently claimed asylum during their stay in 2002. He became a naturalized U.S. citizen on September 11, 2012.[11] At the time of the bombings, Tsarnaev was a student at University of Massachusetts Dartmouth. Previously, Tsarnaev had attended Cambridge Rindge and Latin School.
Following the bombings, on April 18, the Tsarnaev brothers shot and killed MIT Police Officer Sean Collier in a failed attempt to steal his firearm. Later that night, they engaged in a shootout with the police. Tamerlan was killed and a Massachusetts Bay Transportation Authority Police officer was critically injured in the course of the escape in an SUV.[12][13] Dzhokhar was injured but escaped, and a manhunt ensued, with thousands of police searching a 20-block area of Watertown, Massachusetts.
On the evening of April 19, Tsarnaev was found seriously wounded and unarmed hiding in a boat on a trailer in Watertown just outside the police perimeter. After the police opened fire at the boat, they arrested him and took him to Beth Israel Deaconess Medical Center. Tsarnaev was charged on April 22 with using and conspiring to use a weapon of mass destruction resulting in death and with malicious destruction of property resulting in death.[1][14][15] Tsarnaev later said during questioning that the brothers next intended to detonate explosives in Times Square in New York City.[16] Tsarnaev reportedly also told authorities that he and his brother were inspired, at least in part, by watching lectures by Anwar al-Awlaki.[17] He was convicted on April 8, 2015 and sentenced to death on June 24, 2015.[18][19][20] His death sentence was vacated on appeal in July 2020, but the U.S. Supreme Court reversed this decision in March 2022.[21][22] 041b061a72