Since its initial cloning in 2002, a plethora of studies in a vast number of cancer indications, has strongly established AEG-1 as a bona fide oncogene. In all types of cancer cells, overexpression and knockdown studies have demonstrated that AEG-1 performs a seminal role in regulating proliferation, invasion, angiogenesis, metastasis and chemoresistance, the defining cancer hallmarks, by a variety of mechanisms, including protein-protein interactions activating diverse oncogenic pathways, RNA-binding promoting translation and regulation of inflammation, lipid metabolism and tumor microenvironment. These findings have been strongly buttressed by demonstration of increased tumorigenesis in tissue-specific AEG-1 transgenic mouse models, and profound resistance of multiple types of cancer development and progression in total and conditional AEG-1 knockout mouse models. Additionally, clinicopathologic correlations of AEG-1 expression in a diverse array of cancers establishing AEG-1 as an independent biomarker for highly aggressive, chemoresistance metastatic disease with poor prognosis have provided a solid foundation to the mechanistic and mouse model studies. In this review a comprehensive analysis of the current and up-to-date literature is provided to delineate the clinical significance of AEG-1 in cancer highlighting the commonality of the findings and the discrepancies and discussing the implications of these observations.

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Patient: Male, 55Final Diagnosis: Type-A aortic dissectionSymptoms: Exertional dyspnea • orthopneaMedication: —Clinical Procedure: Emergent surgical repair with mesh implantSpecialty: CardiologyObjective:Unusual clinical courseBackground:Aortic dissection presents with acute chest or back pain and is associated with high mortality. We present a case of aortic dissection with an atypical presentation in a peritoneal dialysis patient, and the challenges met with peritoneal dialysis.Case Report:A 53-year-old African American male presented with progressively worsening exertional dyspnea and orthopnea for 3 days without any history of chest pain. His chest x-ray showed mild pulmonary edema. He was admitted with a diagnosis of heart failure. Bedside echocardiogram revealed severe aortic regurgitation and concern for possible aortic dissection. Computed tomography of chest with contrast showed Stanford type-A aortic dissection extending from the aortic valve to the level of the left subclavian artery. Emergent surgery was performed. Postoperatively, the patient was managed in surgical and trauma intensive care unit to keep the blood pressure in the desired range. Initially, he was started on continuous veno-venous hemodialysis and later on transitioned to intermittent hemodialysis. He was switched back to peritoneal dialysis after 6 weeks of surgery.Conclusions:Atypical presentation of a silent aortic dissection without chest pain in the setting of renal failure and other comorbidities emphasizes that dialysis patients are different from the general population. Sometimes the management needs to be modified from the conventional ways to achieve the high level of success.

Case:A 62-year-old male presented with a two-week history of right-sided weakness. Brain MRI showed multiple ring-enhancing lesions consistent with metastatic disease and one lesion with a hemorrhagic component. Chest x-rays showed a 7.6-cm mass in the upper right lobe (Fig. 1, arrow) and bilateral nodular densities. A followup chest CT showed a lobulated mass measuring 9.9 9 6.0 9 6.3 cm in the upper right lobe and multiple pulmonary nodules bilaterally. In addiFigure 1. Chest x-rays showing a large mass in the upper right lobe (arrow).Figure 2. Chest CT showing a large filling defect in the right ventricle (arrow). LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.Figure 3. Transthoracic echocardiography in apical 4-chamber view showing a large (7.8 9 4.4 cm) mass in the right ventricle (arrow). LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

Immune reconstitution is critical to long term survivability in recipients of allogeneic hematopoietic cell transplantation (HCT), mitigating both relapse as well as infection risk. However, both graft versus host disease (GVHD) and post HCT immunosuppression used to prevent it impair immune recovery, particularly functional B cell reconstitution which may not happen for several months post-transplant. This is relevant for post-transplant vaccination which in some centers is delayed till immune cell recovery. In this retrospective, Virginia Commonwealth University institutional review board (IRB) approved study, T helper and B cell recovery for up to two years following HCT was evaluated in 212 patients transplanted between 2015 and 2019. There were 69 HLA matched related & 143 unrelated donor transplant recipients. Median age of the patients was 56 years (range 19-74); conditioning regimens utilized were reduced intensity (RIC) in ~62% of the patients and rabbit anti-thymocyte globulin was used in ~72% of the patients. Blood stem cells were given in 183 patients and bone marrow in 29. Only patients with hematological malignancies were included in this study. Landmark analysis was carried out, with patients who did not survive the first 6 months post-transplant excluded. Of these patients, 85% are surviving. Median CD3+/4+ (Th) cell counts were 153 at 6 months, 228 at 1-year, 296 at 2 years, and corresponding B cell counts were 70, 175, & 273. Plotting Th and B cell counts over time in each individual donor-recipient pair demonstrated close correspondence between Th and B cell recovery, with synchronous recovery observed in most patients, median R 0.76 (range: 0.01-0.99). The slope of the B/Th cell curves for each patient then were compared in a subset of patients, and demonstrated a significant difference between those patients who either did not develop GVHD or only had acute GVHD as opposed to those who developed both acute and chronic GVHD (1.3±1.4 B cells/Th cells and 1.1±1.2 vs. 0.5±1, P=0.02 and 0.06 respectively), suggesting poor B cell recovery in those with chronic GVHD. Different immune recovery kinetics were observed amongst patients (Figure 1); A) rapid B cell recovery, highest absolute B cell count between 30 and 180 days post-HCT, B) intermediate B cell recovery, days 180 and 455, C) delayed B cell recovery, days 455 and 725 days, and D) minimal to no B cell recovery. A higher relative risk for developing acute + chronic GVHD was seen in the intermediate B cell recovery group when compared to those with delayed recovery, RR = 2.38 (95% CI 1.08-5.25). Functional B cell studies were performed in a subset, by measuring IgG levels and anti-pneumococcal antibody titers. Correlation was observed between Th cell count and IgG levels over time in individual patients (median R = 0.57). Pneumococcal titers were also measured at approximately 6 months, 1- and 2-years post-transplant as patients were given a series of PCV13 & PSV23 vaccinations 6 months after HCT. When the antibody titers against unique pneumococcal serotypes were analyzed in individual patients, these varied within each individual, following a declining trend in levels for antibodies against different serotypes; this decline occurred on a logarithmic scale suggesting differential immunogenicity of the pneumococcal antigens, and also mathematically ordered, rather than random Th and B cell responses (Figure 2A). When the serotypes with the highest titers in most patients were correlated with Th and B cell counts measured simultaneously, no association was observed. Further, when fold increase in pneumococcal titers beyond 1-year post transplant were compared across different groups of patients based on their GVHD status, no significant difference was observed in their antibody responses (Figure 2B). In conclusion, our data suggest synchronous Th and B cell reconstitution post allogeneic HCT, both in numeric and functional terms, and thus strategies to help promote T cell recovery, such as IL-7 administration post-transplant, are necessary to encourage optimal immune reconstitution. Vaccine responses beyond 6 months, as in the institutional practice reported here, are independent of GVHD status and numeric immune cellular recovery. These findings are consistent with the notion that immune recovery is a dynamical, rather than a stochastic process. Disclosures No relevant conflicts of interest to declare.