Primary graft dysfunction (PGD) is a major complication following lung transplantation. We reported that anti-type V collagen (col(V)) T cell immunity was strongly associated with PGD. However, the role of preformed anti-col(V) Abs and their potential target in PGD are unknown. Col(V) immune serum, purified IgG or B cells from col(V) immune rats were transferred to WKY rat lung isograft recipients followed by assessments of lung pathology, cytokines, and PaO2/FiO2, an index of lung dysfunction in PGD. Immune serum, purified IgG, and B cells all induced pathology consistent with PGD within 4 days posttransfer; up-regulated IFN-γ, TNF-α, and IL-1β locally; and induced significant reductions in PaO2/FiO2. Depleting anti-col(V) Abs before transfer demonstrated that IgG2c was a major subtype mediating injury. Confocal microscopy revealed strong apical col(V) expression on lung epithelial, but not endothelial cells; which was consistent with the ability of col(V) immune serum to induce complement-dependent cytotoxicity only in the epithelial cells. Examination of plasma from patients with or without PGD revealed that higher levels of preformed anti-col(V) Abs were strongly associated with PGD development. This study demonstrates a major role for anti-col(V) humoral immunity in PGD, and identifies the airway epithelium as a target in PGD.
The V antigen (LcrV) of the plague bacterium Yersinia pestis is a potent protective antigen that is under development as a vaccine component for humans. LcrV is multifunctional. On the bacterial surface it mediates delivery of a set of toxins called Yops into host cells, and as a released protein it can cause production of the immunosuppressive cytokine interleukin-10 (IL-10) and can inhibit chemotaxis of polymorphonuclear neutrophils. It is not known how these mechanisms of LcrV operate, what their relative importance is, when they function during plague, and which are critical to protection by antibody. This study investigated several of these issues. C57BL/6 mice, mice unable to express IL-10, or mice with the macrophage lineage eliminated were treated with a protective anti-LcrV antibody or a nonprotective antibody against YopM and infected intravenously by Y. pestis KIM5 or a strain that lacked the genes encoding all six effector Yops. Viable bacterial numbers were determined at various times. The data indicated that Yops were necessary for Yersinia growth after the bacteria had seeded liver and spleen. Anti-LcrV antibody prevented this growth, even in IL-10 ؊/؊ mice, demonstrating that one protective mechanism for anti-LcrV antibody is independent of IL-10. Anti-LcrV antibody had no effect on persistence in organs of Y. pestis lacking effector Yops, even though the yersiniae could strongly express LcrV, suggesting that Yops are necessary for building sufficient bacterial numbers to produce enough LcrV for its immunosuppressive effects. In vitro assays showed that anti-LcrV antibody could partially block delivery of Yops and downstream effects of Yops in infected macrophage-like J774A.1 cells. However, cells of the macrophage lineage were found to be dispensable for protection by anti-LcrV antibody in spleen, although they contributed to protection in liver. Taken together, the data support the hypothesis that one protective effect of the antibody is to block delivery of Yops to host cells and prevent early bacterial growth. The findings also identified the macrophage lineage as one host cell type that mediates protection.
Patient: Female, 67Final Diagnosis: Breast angiosarcomaSymptoms: Skin lesionMedication: —Clinical Procedure: SurgerySpecialty: OncologyObjective:Unusual clinical courseBackground:Radiation-associated breast angiosarcoma is a rare clinical entity that is thought to be increasing in incidence.Case Report:Here we present the case of a 67-year-old female with a history of left breast invasive ductal carcinoma who received breast conserving surgery and radiation therapy eight years ago. She then presented with a painless mild skin discoloration of the left breast that had been present for over one year. Mammograms and ultra-sounds were normal. A punch biopsy and a subsequent excisional biopsy revealed the diagnosis of angiosarcoma. The patient was treated with mastectomy and had no subsequent recurrences.Conclusions:The long-term clinical surveillance for all patients who receive breast conservation surgery is recommended and a high degree of suspicion should be exercised in view of potential atypical presentations of this disease.
Background The Texas/Chihuahua (US/Mexico) border is a medically underserved region with many reported barriers for health care access. Although Hispanic ethnicity is associated with health disparities for many different diseases, the population‐based estimates of incidence and survival for patients with blood cancer along the border are unknown. The authors hypothesized that Hispanic ethnicity and border proximity is associated with poor blood cancer outcomes. Methods Data from the Texas Cancer Registry (1995‐2016) were used to investigate the primary exposures of patient ethnicity (Hispanic vs non‐Hispanic) and geographic location (border vs non‐border). Other confounders and covariates included sex, age, year of diagnosis, rurality, insurance status, poverty indicators, and comorbidities. The Mantel‐Haenszel method and Cox regression analyses were used to determine adjusted effects of ethnicity and border proximity on the relative risk (RR) and survival of patients with different blood cancer types. Results Hispanic patients were diagnosed at a younger age than non‐Hispanic patients and presented with increased comorbidities. Whereas non‐Hispanics had a higher incidence of developing blood cancer compared with Hispanics overall, Hispanics demonstrated a higher incidence of acute lymphoblastic leukemia (RR, 1.92; 95% CI, 1.79‐2.08; P < .001) with worse outcomes. Hispanics from the Texas/Chihuahua border demonstrated a higher incidence of chronic myeloid leukemia (RR, 1.28; 95% CI, 1.07‐1.51; P = .02) and acute myeloid leukemia (RR, 1.17; 95% CI, 1.04‐1.33; P = .0009) compared with Hispanics living elsewhere in Texas. Conclusions Hispanic ethnicity and border proximity were associated with a poor presentation and an adverse prognosis despite the younger age of diagnosis. Future studies should explore differences in disease biology and treatment strategies that could drive these regional disparities.
Background/Aim: The aim of the study was to investigate the efficacy of neoadjuvant and chemotherapy (NACT) and adjuvant chemotherapy (ACT) in Hispanic/Latino (H/L) women with TNBC. Patients and Methods: We reviewed the charts of patients with TNBC, stages I-III, treated at TTUHSC from 2006 to 2016. Overall survival (OS) and recurrence-free survival (RFS) were estimated and compared between the treatment groups. Kaplan-Meier curve and Cox proportional hazards regression analyses were conducted to estimate unadjusted and adjusted effects of NACT compared to ACT. Results: A total of 104 patients with TNBC, 30 (29%) received NACT and 74 (71%) ACT. Women undergoing NACT were younger, with a mean age of 50.8 years. Of the 30 patients who received NACT, 12 (40%) had pathologically complete response (pCR). Women who achieved pCR had an excellent RFS (HR=0.5, p=0.001). Women with residual cancer after NACT had worse outcome compared to patients who received ACT (HR=1.7, p=0.005). Conclusion: pCR to NACT is a powerful surrogate for OS in H/L women with TNBC. Breast cancer is the second leading cause of cancer death after lung cancer. In 2019, the American Cancer Association estimated that there were 252,700 new cases of breast cancer in the United States and 41,000 deaths from the disease (1, 2). Breast cancer is a heterogeneous disease, biologically characterized by the expression of one or more steroid hormone receptors such as estrogen receptor (ER) or progesterone receptor (PR) along with the oncogeneepidermal growth factor receptor ErbB2 (Her-2neu). Of those subtypes, triple-negative breast cancer (TNBC) is biologically defined by the absence of expression of ER, PR, and Her-2neu receptors (3). It is a heterogenic subgroup of breast cancer that comprises approximately 15% of all types of breast cancer. TNBC is highly aggressive and has worse disease-specific outcomes than any other subtype of breast cancer (3, 4). One possible explanation is the absence of well-defined molecular targets such as ER, PR, or Her2-neu, which limits options for treating this subtype of breast cancer. Systemic chemotherapy has remained the only available option for these patients for almost two decades. Historically, NACT has been used to downstage unresectable breast cancer to allow for better locoregional control and to increase the chance for breast-conserving surgery. It has been recognized that NACT represents an excellent in vivo approach to directly test tumor sensitivity to chemotherapy. Unfortunately, the large National Surgical Adjuvant Breast and Bowel Project (NSABP) randomized clinical trial B-18 did not show any statistically significant difference in the overall survival (OS) between patients who underwent NACT and those who underwent adjuvant chemotherapy (ACT) (5). There was, however, a trend in favor of NACT in women younger than 50 years of age. The major limitation of the B-18 trial was the lack of subgroup analysis by hormonal status. Furthermore, multiple published retrospective clinical studies comparing the efficacy...
The mean age was 61.6±9.4 years, and 109 (91.6%) selfidentified as Hispanic/Latino. A total of 58% reported an annual income of $15,000 or less. Overall, 40.3% had completed eighth grade or less education, 31.9% high school, and 12% had obtained a technical degree. The majority of patients (56%) had either a medium (45%) or a low level of adherence (11%). High adherence was noted in 44% of participants. Seven (5.6%) patients scored 2 or below on a 4-point scale for intentional adherence, and 18 (13.5%) scored 2 or below on a 4-point scale for unintentional adherence. Conclusion: These data suggest that the majority of Hispanic/Latino women with breast cancer have medium or low levels of adherence to therapy with AIs. Factors associated with medium and low adherence were unintentional (forgetfulness), but also included intentional factors, such as avoidance of adverse effects and delays with obtaining refills (cost-related nonadherence). Breast cancer (BC) is the second leading cause of cancer death after lung cancer in the United States (1). In 2018, the American Cancer Association estimated that there were 252,700 new cases of BC in the United States and 41,000 deaths from the disease (1). It is the major type of cancer among Hispanic/Latino women in the United States, with approximately 20,000 new cases and 3,000 deaths per year(2). From 2003 to 2018, the incidence rate of BC remained stable in both Hispanic and non-Hispanic White women (2). The use of screening mammography and advances in treatment modalities including the use of adjuvant endocrine therapy have contributed to the reduction of mortality from BC in the United States by approximately 24% since 1990 (3). Multiple studies have shown substantial benefits from adjuvant endocrine therapy in improving progression-free and overall survival (4-7). For almost two decades, adjuvant endocrine therapy with an aromatase inhibitor (AI) has remained a gold-standard for patients with hormonal receptor-positive BC. In 2003, the first results of ATAC (arimidex, tamoxifen, alone or in combination) phase 857 This article is freely accessible online.
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