Use of a dual lumen port for automated red cell exchange in adults with sickle cell disease

Red cell exchange (RCE) is a common procedure in adults with sickle cell disease (SCD). Implantable dual lumen Vortex (DLV) ports can be used for RCE in patients with poor peripheral venous access. We performed a retrospective cohort study of RCE procedures performed in adults with SCD. The main objective of the study was to compare the inlet speed, duration of procedures and rate of complications performed through DLV ports to those performed through temporary central venous and peripheral catheters. Twenty‐nine adults with SCD underwent a total of 318 RCE procedures. Twenty adults had DLV ports placed and 218 procedures were performed using DLV ports. Mean length of follow‐up after DLV port placement was 397 ± 263 days. Six DLV ports were removed due to infection and 1 for malfunction after a mean of 171 ± 120 days. Compared to temporary central venous and peripheral catheters, DLV port procedures had a greater rate of procedural complications, a longer duration, and a lower inlet speed (all P < 0.01). When accounting for the maximum allowable inlet speed to avoid citrate toxicity, 40% of DLV port procedures were greater than 10% below maximum speed, compared to 7 and 14% of procedures performed through temporary central venous and peripheral catheters (P < 0.0001). In conclusion, DLV ports can be used for RCE in adults with SCD, albeit with more procedural complications and longer duration. The smaller internal diameter and longer catheter of DLV ports compared to temporary central venous catheters likely accounts for the differences noted. J. Clin. Apheresis 30:353–358, 2015. © 2015 Wiley Periodicals, Inc.     

Maximizing Breast Cancer Therapy with Awareness of Potential Treatment-Related Blood Disorders

In this review we summarize the impact of the various modalities of breast cancer therapy coupled with intrinsic patient factors on incidence of subsequent treatment-induced myelodysplasia and acute myelogenous leukemia (t-MDS/AML). It is clear that risk is increased for patients treated with radiation and chemotherapy at younger ages. Radiation is associated with modest risk, whereas chemotherapy, particularly the combination of an alkylating agent and an anthracycline, carries higher risk and radiation and chemotherapy combined increase the risk markedly. Recently, treatment with granulocyte colony-stimulating factor (G-CSF), but not pegylated G-CSF, has been identified as a factor associated with increased t-MDS/AML risk. Two newly identified associations may link homologous DNA repair gene deficiency and poly (ADP-ribose) polymerase inhibitor treatment to increased t-MDS/AML risk. When predisposing factors, such as young age, are combined with an increasing number of potentially leukemogenic treatments that may not confer large risk singly, the risk of t-MDS/AML appears to increase. Patient and treatment factors combine to form a biological cascade that can trigger a myelodysplastic event. Patients with breast cancer are often exposed to many of these risk factors in the course of their treatment, and triple-negative patients, who are often younger and/or BRCA positive, are often exposed to all of them. It is important going forward to identify effective therapies without these adverse associated effects and choose existing therapies that minimize the risk of t-MDS/AML without sacrificing therapeutic gain.

Implications for Practice

Breast cancer is far more curable than in the past but requires multimodality treatment. Great care must be taken to use the least leukemogenic treatment programs that do not sacrifice efficacy. Elimination of radiation and anthracycline/alkylating agent regimens will be helpful where possible, particularly in younger patients and possibly those with homologous repair deficiency (HRD). Use of colony-stimulating factors should be limited to those who truly require them for safe chemotherapy administration. Further study of a possible leukemogenic association with HRD and the various forms of colony-stimulating factors is badly needed.

     

A Reminder of Methylene Blue's Effectiveness in Treating Vasoplegic Syndrome after On-Pump Cardiac Surgery

The inflammatory response induced by cardiopulmonary bypass decreases vascular tone, which in turn can lead to vasoplegic syndrome. Indeed the hypotension consequent to on-pump cardiac surgery often necessitates vasopressor and intravenous fluid support. Methylene blue counteracts vasoplegic syndrome by inhibiting the formation of nitric oxide.We report the use of methylene blue in a 75-year-old man who developed vasoplegic syndrome after cardiac surgery. After the administration of methylene blue, his hypotension improved to the extent that he could be weaned from vasopressors. The use of methylene blue should be considered in patients who develop hypotension refractory to standard treatment after cardiac surgery.     

Group testing in mediation analysis

We consider the scenario where there is an exposure, multiple biologically defined sets of biomarkers, and an outcome. We propose a new two-step procedure that tests if any of the sets of biomarkers mediate the exposure/outcome relationship, while maintaining a prespecified familywise error rate. The first step of the proposed procedure is a screening step that removes all groups that are unlikely to be strongly associated with both the exposure and the outcome. The second step adapts recent advances in postselection inference to test if there are true mediators in each of the remaining candidate sets. We use simulation to show that this simple two-step procedure has higher statistical power to detect true mediating sets when compared with existing procedures. We then use our two-step procedure to identify a set of Lysine-related metabolites that potentially mediate the known relationship between increased body mass index and the increased risk of estrogen-receptor positive breast cancer in postmenopausal women.     

Peripheral Vascular Complication from Coronary Angiography: a Case Report of Cholesterol Embolization

A 65-year-old man developed acute limb ischemia, severe abdominal wall and lower limb livedo reticularis following a coronary angiogram. The differential diagnoses of acute limb ischemia and multiple cholesterol emboli syndrome (MCES) are discussed. This work was performed at Long Island Jewish Medical Center, 270-05, 76^th Avenue, New Hyde Park, NY 11040.     

Novel explant model to study mechanotransduction and cell-cell communication.

To understand in situ behavior of osteocytes, we characterized a model of osteocytes in their native bone matrix and demonstrated real-time biologic activity of osteocytes while bending the bone matrix. Using 43 male Sprague-Dawley rats, dumbbell-shaped explants were harvested from stainless steel femoral implants after 6-12 weeks and incubated in culture medium or fixed. Sixteen specimens were used to determine bone volume density (BV/TV), volumetric bone mineral density (BMD) and histology for different implantation periods. Osteocyte viability was evaluated by L-lactate dehydrogenase (LDH) activity in 12 cultured explants. Confocal microscopy was used to assess tracer diffusion in three explants and changes in osteocyte pH of a mechanically loaded explant. From 6 to 12 weeks, explant BV/TV and volumetric BMD trended up 92.5% and 101%, respectively. They were significantly and highly correlated. Tissues were uniformly intramembranous and all bone cell types were present. Explants maintained LDH activity through culture day 8. Diffusion at 200 microM was limited to 1,209 Da. Explants appeared capable of reproducing complex bone biology. This model may be useful in understanding osteocyte mechanotransduction in the context of a physiologically relevant bone matrix.     

Sentinel health events surveillance in diabetes. Deaths among persons under age 45 with diabetes

The pilot study for a sentinel health events surveillance system for deaths among persons under age 45 with diabetes was conducted in six states in 1984 and 1985. Two hundred and thirty-three events were identified. Information from death certificates, physicians, and families revealed that 22% died from acute complications of diabetes and 53% from chronic complications. Blood pressure measurement and urinalysis testing had been performed in the last year for almost all of the decedents, but other preventive practices were reported less frequently. Hypertension was present in 57% and of those, was not controlled in 73%. Forty-four percent were cigarette smokers at the time of death. Agreement between physicians and families was generally higher for clinical conditions than for care practices. This surveillance system appears to yield information about the health care of persons with diabetes not readily available from other sources, although modifications may be necessary before implementation.