Pretransplant Chromosome Genomic Array Testing Improves Prognostication for Myelofibrosis Patients Undergoing Transplantation.

Background: Despite its known superior diagnostic yield for chromosomal anomalies compared with karyotype and fluorescence in situ hybridization (FISH) studies, chromosome genomic array testing (CGAT) is not used as a routine clinical test for myelofibrosis. Although many prognostic systems exist that risk stratify patients at diagnosis, limited tools are available to prognosticate transplant outcome.

Objective: The current study aimed at testing whether CGAT results obtained before transplantation improves prognosis of post-transplant outcome in patients with myelofibrosis compared with current risk categorization systems, for example, DIPSS plus (Dynamic International Prognostic Scoring System).

Mutual Emotional Labor as Method: Building Connections of Care in Qualitative Research.

Emotional labor may be vital to the success of qualitative research studies, particularly longitudinal studies that depend on the maintenance of research relationships over time. Rather than being limited to the comportment of researchers toward their participants, however, we find that participants also actively engage in practices of emotional labor to manage researchers and guide research interactions. We document elements of such "mutual emotional labor" in the establishment of rapport, in crafting experiences of personalized therapeutic benefit from participating in interviews, and in efforts to navigate closure at the conclusion of research projects.

Discovery of U2AF1 neoantigens in myeloid neoplasms.

Background: Myelodysplastic syndromes (MDS) arise from somatic mutations acquired in hematopoietic stem and progenitor cells, causing cytopenias and predisposing to transformation into secondary acute myeloid leukemia (sAML). Recurrent mutations in spliceosome genes, including , are attractive therapeutic targets as they are prevalent in MDS and sAML, arise early in neoplastic cells, and are generally absent from normal cells, including normal hematopoietic cells. MDS and sAML are susceptible to T cell-mediated killing, and thus engineered T-cell immunotherapies hold promise for their treatment.

Speculating on Precarious Income: Finance Cultures and the Risky Strategies of Healthy Volunteers in Clinical Drug Trials.

Speculation has become a normalized occupational strategy and quotidian economic rationality that extends throughout society. Although there are many contemporary articulations of speculation, this article focuses on contract labor as a domain of financialization. Seen through this lens, contract labor can be understood as a speculative investment strategy wherein individuals leverage whatever assets they have at their disposal-savings, time, bodily health-to capture economic advantages.

Early Mixed Lymphoid Donor/Host Chimerism is Associated with Improved Transplant Outcome in Patients with Primary or Secondary Myelofibrosis.

We investigated risk factors for the development of mixed chimerism in 131 patients who underwent transplantation for myelofibrosis and determined the impact of lymphoid (CD3+) and myeloid (CD33+) chimerism on transplant outcome. Disease risk included DIPSS plus categories low to high. The median patient age was 58 years.

Sacrificial Labour: Social Inequality, Identity Work, and the Damaging Pursuit of Elusive Futures.

This article explores the relationship between personal sacrifice and identity work within conditions of profound structural insecurity. We develop the concept of to describe how individual self-sacrifice aligns workers' identities to the needs of organizations while gradually foreclosing the actualization of individuals' desired future selves. Drawing upon qualitative data from a longitudinal study of healthy individuals who enrol in paid clinical trials for the pharmaceutical industry, we make two contributions to the identity-work literature.

Picking and Choosing Among Phase I Trials : A Qualitative Examination of How Healthy Volunteers Understand Study Risks.

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions.

Does perfusion matter? Preoperative prediction of incisional hernia development.

Purpose: Incisional hernias complicate 12-15% of general surgery cases with higher rates reported after laparotomy for aortoiliac occlusive disease (10-17%) and aneurysmal disease (17-38%). We hypothesize that inadequate perfusion of the abdominal wall promotes future hernia development.

Methods: Thirty-eight patients undergoing midline laparotomy or thoracoabdominal approach for aortic disease with at least 2 years of follow-up were included in the study.

Impact of clinical, cytogenetic, and molecular profiles on long-term survival after transplantation in patients with chronic myelomonocytic leukemia.

Chronic myelomonocytic leukemia (CMML) is a heterogeneous group of clonal hematopoietic malignancies with variable clinical and molecular features. We analyzed long-term results of allogeneic hematopoietic cell transplantation in patients with CMML and determined clinical and molecular risk factors associated with outcomes. Data from 129 patients, aged 7-74 (median 55) years, at various stages of the disease and transplanted from related or unrelated donors were analyzed.

Considerations beyond Stenosis for Carotid Endarterectomy in Treating Free-Floating Thrombus of the Carotid Artery.

Background: Free-floating thrombus (FFT) of the carotid artery is an uncommon condition that can present with neurologic symptoms, often in the setting of ischemic stroke. The literature pertaining to the incidence and optimal treatment of this condition is limited. Herein, we report our contemporary experience with FFT across a range of degrees of carotid stenosis.

The myristoylated alanine-rich C kinase substrate differentially regulates kinase interacting with stathmin in vascular smooth muscle and endothelial cells and potentiates intimal hyperplasia formation.

Objective: Restenosis limits the durability of all cardiovascular reconstructions. Vascular smooth muscle cell (VSMC) proliferation drives this process, but an intact, functional endothelium is necessary for vessel patency. Current strategies to prevent restenosis employ antiproliferative agents that affect both VSMCs and endothelial cells (ECs).

A Unique Bailout Method for the Repair of Abdominal Aortic Aneurism with a Narrow Iliac Bifurcation.

Background: Endovascular aneurysm repair (EVAR) became the procedure of first choice for the repair of the abdominal aortic aneurysms (AAAs) in the last decades. However, narrow distal aorta remains to be the main limiting factor for the use of EVAR. A limited number of bail-out procedures have been described in the literature to overcome this problem.

Small GTPases and Their Role in Vascular Disease.

Over eighty million people in the United States have cardiovascular disease that can affect the heart causing myocardial infarction; the carotid arteries causing stroke; and the lower extremities leading to amputation. The treatment for end-stage cardiovascular disease is surgical-either endovascular therapy with balloons and stents-or open reconstruction to reestablish blood flow. All interventions damage or destroy the protective inner lining of the blood vessel-the endothelium.

Prospective study of cryopreserved placental tissue wound matrix in the management of chronic venous leg ulcers.

Objective: Chronic venous leg ulcers (VLUs) affect up to 2% of the general population, resulting in a significant socioeconomic burden. Placental tissue that contains mesenchymal stem cells and active growth factors has been shown to be beneficial in healing of chronic wounds. We compared the efficacy of a human viable wound matrix (hVWM) of cryopreserved placental tissue for the treatment of refractory VLUs with standard therapy.

Healthy volunteers' perceptions of risk in US Phase I clinical trials: A mixed-methods study.

Background: There is limited research on healthy volunteers' perceptions of the risks of Phase I clinical trials. In order to contribute empirically to long-standing ethical concerns about healthy volunteers' involvement in drug development, it is crucial to assess how these participants understand trial risks. The objectives of this study were to investigate (1) participants' views of the overall risks of Phase I trials, (2) their views of the risk of personally being harmed in a trial, and (3) how risk perceptions vary across participants' clinical trial history and sociodemographic characteristics.

Healthy Volunteers' Perceptions of the Benefits of Their Participation in Phase I Clinical Trials.

Other than the financial motivations for enrolling in Phase I trials, research on how healthy volunteers perceive the benefits of their trial participation is scant. Using qualitative interviews conducted with 178 U.S.

Surgical Scarring after Arterial Bypass, an Etiology of Venous Hypertension.

Venous ulcers can be a chronic debilitating condition with a high rate of recurrence. Herein, we describe a case of a patient who successfully underwent an arterial bypass for rest pain but returned with lower extremity swelling and venous ulcers. Venography demonstrated a focal common femoral vein stenosis due to scarring from the surgical exposure.

Selective CD28 Inhibition Modulates Alloimmunity and Cardiac Allograft Vasculopathy in Anti-CD154-Treated Monkeys.

Background: Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using cytotoxic T lymphocyte antigen 4 Ig based on the hypothesis that the checkpoint immune regulators cytotoxic T lymphocyte antigen 4 and programmed death ligand 1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single-chain anti-CD28 Fv fragment linked to alpha-1 antitrypsin [sc28AT]) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation. Here, we explored the efficacy of combining a 3-week "induction" sc28AT treatment with prolonged CD154 blockade.

A Defined Protocol to Resolving Cannulation Failure during Endovenous Ablation Procedures.

During endovenous ablation for the treatment of insufficient veins, failure to cannulate the entirety of the refluxing vein with the treatment catheter prevents technically successful ablation. In this technique report, we describe a defined protocol to overcome cannulation failure of axial veins for endovenous ablation. This protocol utilizes commonly available adjunctive techniques including ultrasound-guided digital compression, the use of a guidewire, the use of a guide catheter, and placement of a second puncture site in a step-wise fashion to overcome varying degrees of tortuosity or obstruction.

Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function.

Arterial reconstruction, whether angioplasty or bypass surgery, involves iatrogenic trauma causing endothelial disruption and vascular smooth muscle cell (VSMC) proliferation. Common murine models study small vessels such as the carotid and femoral arteries. Herein we describe an in vivo system in which both VSMC proliferation and endothelial barrier function can be simultaneously assessed in a large vessel.

Double prepuncture as a valuable adjunctive technique for complex endovenous ablation.

Objective: The objective of this study was to characterize the technique and to report the results of double prepuncture used during complex radiofrequency ablation (RFA) in cases of treating multiple incompetent veins or encountering focal obstruction to catheter advancement.

Methods: A double prepuncture technique was applied in patients requiring endovascular ablation of multiple veins and patients with great saphenous vein cannulation failure. We treated 13 limbs in 12 patients during a 24-month period with RFA in which the double prepuncture technique was used.

Strategies for Obtaining Access to Secretive or Guarded Organizations.

Establishing contacts and gaining permission to conduct ethnographic or qualitative research can be time-consuming and stressful processes. Gaining access can be especially challenging when representatives of prospective research sites see their work as being sensitive and would prefer to avoid outside scrutiny altogether. One result of this dynamic is that many organizations that exert a profound influence in governing populations and regulating individuals' access to basic needs are relatively invisible to the public and shielded from meaningful public accountability.

MARCKS Signaling Differentially Regulates Vascular Smooth Muscle and Endothelial Cell Proliferation through a KIS-, p27kip1- Dependent Mechanism.

Background: Overexpression of the myristolated alanine-rich C kinase substrate (MARCKS) occurs in vascular proliferative diseases such as restenosis after bypass surgery. MARCKS knockdown results in arrest of vascular smooth muscle cell (VSMC) proliferation with little effect on endothelial cell (EC) proliferation. We sought to identify the mechanism of differential regulation by MARCKS of VSMC and EC proliferation in vitro and in vivo.

Myristoylated Alanine-Rich Protein Kinase Substrate (MARCKS) Regulates Small GTPase Rac1 and Cdc42 Activity and Is a Critical Mediator of Vascular Smooth Muscle Cell Migration in Intimal Hyperplasia Formation.

Background: Transcription of the myristoylated alanine-rich C kinase substrate (MARCKS) is upregulated in animal models of intimal hyperplasia. MARCKS knockdown inhibits vascular smooth muscle cell (VSMC) migration in vitro; however, the mechanism is as yet unknown. We sought to elucidate the mechanism of MARCKS-mediated motility and determine whether MARCKS knockdown reduces intimal hyperplasia formation in vivo.