Gamified versus non-gamified online educational modules for teaching clinical laboratory medicine to first-year medical students at a large allopathic medical school in the United States.

BACKGROUND: Medical educators seek innovative ways to engage learners efficiently and effectively. Gamification has been explored as one way to accomplish this feat; however, questions remain about which contexts gamification would be most useful. Time constraints and student interest present major barriers for teaching laboratory medicine to students. This study aims to compare two versions of an interactive online module, one gamified and one not, for teaching laboratory medicine concepts to pre-clinical medical students. METHODS: First-year medical students reviewed either a gamified or non-gamified version of an interactive online module in preparation for an in-person flipped classroom session on Laboratory Medicine. Learning theory guided the design of the modules and both contained identical content, objectives, and structure. The "gamified" module included the additional elements of personalization, progress meters, points, badges, and story/role play. After reviewing the module, students completed an anonymous knowledge check and optional survey. RESULTS: One hundred seventy-one students completed the post module knowledge check as assigned (82 gamified, 89 non-gamified). Knowledge check scores were higher for the students who reviewed the gamified module (p < 0.02), corresponding to an effect size of 0.4 for the gamified module. Eighty-one students completed optional post-module surveys (46 gamified, 35 non-gamified). Instructional efficiency was calculated using task difficulty questions and knowledge check scores, and the resulting instructional efficiency was higher for the gamified module. There was no significant difference in the student-reported time required to complete the modules. Additionally, both versions of the module were well received and led to positive ratings related to motivation and confidence. Finally, examination of open-ended survey results suggested that the addition of game elements added value to the gamified module and enhanced engagement and enjoyment. CONCLUSIONS: In this setting, the addition of gamification to an interactive online module enhanced learning outcome, instructional efficiency, student engagement and enjoyment. These results should inspire further exploration of gamification for teaching Laboratory Medicine concepts to pre-clinical medical students.

Use of therapeutic plasma exchange for pediatric neurological diseases.

Therapeutic plasma exchange is used to treat neurological diseases in the pediatric population. Since its first use in pediatric patients with hepatic coma in the form of manual whole blood exchange, therapeutic plasma exchange has been increasingly used to treat these disorders of the nervous system. This expansion is a result of improved techniques and apheresis instruments suitable for small children, as well as the recognition of its applicability to many diseases in the pediatric population. This review provides a historical overview of the use of therapeutic apheresis in children and highlights the most common applications for therapeutic plasma exchange to treat neurological disorders in children.

Changes in Mean Corpuscular Volume and RBC Distribution Width Predict Erythrocyte Engraftment Following ABO-Incompatible Hematopoietic Stem Cell Transplantation.

OBJECTIVES: The purpose of this study was to identify laboratory parameters representing erythrocyte engraftment to be used as an indicator to change the recipient to donor ABO group and Rh type following an ABO-incompatible hematopoietic stem cell transplant (HSCT). Studies have shown that ABO incompatibility does not have an effect on outcome of HSCT; however, the serologic consequences of these ABO-incompatible transplants can make it difficult to decide when to begin support with donor ABO/Rh-type blood products. METHODS: This study explored the use of RBC distribution width (RDW), mean corpuscular volume, and hemoglobin as regularly tested laboratory parameters that could be used as surrogate markers for RBC engraftment in 65 patients who received ABO/Rh-incompatible HSCT. RESULTS: The appearance of engrafted donor RBCs correlated with a peak in RDW (P = .002). In addition, our findings suggest that serologic changes in ABO/Rh appear to correspond with a peak in RDW (P = .002). CONCLUSIONS: High values of RDW likely result from a substantial proportion of large, young erythrocytes from recent engraftment with smaller, older pretransplant erythrocytes from the recipient. Our findings suggest that peak RDW may be an indicator of erythrocyte engraftment, following an ABO/Rh-incompatible HSCT.

Therapeutic plasma exchange for neuromyelitis optica spectrum disorder: A multicenter retrospective study by the ASFA neurologic diseases subcommittee.

IMPORTANCE: Neuromyelitis optica/neuromyelitis optica spectrum disorder patients' response to therapeutic plasma exchange (TPE) is currently incompletely characterized. OBJECTIVE: Our study aims to understand the clinical status improvement of neuromyelitis optica/neuromyelitis optica spectrum disorder patients treated with TPE. DESIGN, SETTING, AND PARTICIPANTS: This is a multicenter retrospective study conducted between 1 January 2003 and 31 July 2017 at 13 US hospitals performing apheresis procedures. Subjects studied were diagnosed with neuromyelitis optica/neuromyelitis optica spectrum disorder who received TPE during presentation with acute disease. MAIN OUTCOMES AND MEASURES: The primary outcome was clinical status improvement in patients treated with TPE. Secondary measures were procedural and patient characteristics associated with response to treatment. RESULTS: We evaluated 114 patients from 13 institutions. There was a female predilection. The largest ethnic group affected was non-Hispanic Caucasian. The average age of diagnosis was 43.1 years. The average time to diagnosis was 3.1 years. On average, five procedures were performed during each treatment series. The most commonly performed plasma volume exchange was 1.0 to 1.25 using 5% albumin as replacement fluid. Most patients (52%) did not require an additional course of TPE and noted "mild" to "moderate" clinical status improvement. Maximal symptom improvement appeared by the fourth or fifth TPE treatment. CONCLUSION AND RELEVANCE: TPE improved the clinical status of patients. Adults responded more favorably than children. Procedural characteristics, including number of TPEs, plasma volume exchanged, and replacement fluid used, were similar between institutions. TPE was well-tolerated and had a low severe adverse event profile.

Iron Deficiency Anemia in Patients Undergoing Extracorporeal Photopheresis for Cutaneous T-Cell Lymphoma.

OBJECTIVE: To describe the indicidence and severity of iron deficiency anemia (IDA) in patients who have received extracorporeal photopheresis (ECP) treatment of cutaneous T-cell lymphoma (CTCL). METHODS: We performed a retrospective study during a 9-year period of patients with CTCL who were treated with ECP. ECP was performed with UVAR XTS and CELLEX (Therakos Inc). IDA was defined by a drop in hemoglobin (Hb), mean cell volume (MCV), and increased red blood cell distribution width (RDW). RESULTS: We identified a total of 36 patients; 1 patient was excluded due to severe anemia. In 35 patients, initial hemoglobin values ranged from 9.8 g per dL to 15.9 g per dL, and patients received 4 to 327 ECP treatments. In all, 28 patients showed decreases in Hb of 0.8 g per dL to 6 g per dL during treatments. CONCLUSION: Chronic ECP led to IDA in 28 of 35 patients with CTCL. IDA occurs due to blood loss when ECP equipment does not return full blood volume to patients.

Attenuation of Red Blood Cell Storage Lesions with Vitamin C.

Stored red blood cells (RBCs) undergo oxidative stress that induces deleterious metabolic, structural, biochemical, and molecular changes collectively referred to as "storage lesions". We hypothesized that vitamin C (VitC, reduced or oxidized) would reduce red cell storage lesions, thus prolonging their storage duration. Whole-blood-derived, leuko-reduced, SAGM (saline-adenine-glucose-mannitol)-preserved RBC concentrates were equally divided into four pediatric storage bags and the following additions made: (1) saline (saline); (2) 0.3 mmol/L reduced VitC (Lo VitC); (3) 3 mmol/L reduced VitC (Hi VitC); or (4) 0.3 mmol/L oxidized VitC (dehydroascorbic acid, DHA) as final concentrations. Biochemical and rheological parameters were serially assessed at baseline (prior to supplementation) and Days 7, 21, 42, and 56 for RBC VitC concentration, pH, osmotic fragility by mechanical fragility index, and percent hemolysis, LDH release, glutathione depletion, RBC membrane integrity by scanning electron microscopy, and Western blot for ß-spectrin. VitC exposure (reduced and oxidized) significantly increased RBC antioxidant status with varying dynamics and produced trends in reduction in osmotic fragility and increases in membrane integrity. CONCLUSION: VitC partially protects RBC from oxidative changes during storage. Combining VitC with other antioxidants has the potential to improve long-term storage of RBC.

Impact of high dose vitamin C on platelet function.

AIM: To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). METHODS: Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to: (1) normal saline (control); (2) 0.3 mmol/L VitC (Lo VitC); or (3) 3 mmol/L VitC (Hi VitC, final concentrations) and stored appropriately. The VitC additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of VitC used here correspond to plasma VitC levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography (TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate (ATP) secretion in response to collagen or adenosine diphosphate (ADP); and flow cytometry, for changes in expression of CD-31, CD41a, CD62p and CD63. In addition, PLT intracellular VitC content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time (PT), partial thrombplastin time (PTT), functional fibrinogen] and Lipidomics analysis (UPLC ESI-MS/MS). RESULTS: VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L (Lo VitC) and 15.7 mmol/L (Hi VitC, P < 0.05). VitC supplementation did not significantly change PT and PTT values, or functional fibrinogen levels over the 8 d exposure period (P > 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle (P < 0.05). There was also a fall of 20 mm in maximum amplitude associated with the Hi VitC compared to both baseline and day 8 saline controls. Platelet aggregation studies, showed uniform declines in collagen and ADP-induced platelet aggregations over the 8-d study period in all three groups (P > 0.05). Collagen and ADP-induced ATP secretion was also not different between the three groups (P > 0.05). Finally, VitC at the higher dose (3 mmol/L) also induced the release of several eicosanoids including thromboxane B2 and prostaglandin E2, as well as products of arachidonic acid metabolism via the lipoxygenases pathway such as 11-/12-/15-hydroxyicosatetraenoic acid (P < 0.05). CONCLUSION: Alterations in PLT function by exposure to 3 mmol/L VitC for 8 d suggest that caution should be exerted with prolonged use of intravenous high dose VitC.

Development and Detection of Kidd Antibodies.

Kidd antibodies have a reputation for causing hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. We present a case of an untransfused male patient who developed anti-Kidd(a) (Jk(a)) antibodies after receiving an allogenic renal transplant. The formation of this antibody was associated with exposure to the Kidd antigen expressed on the tubular epithelium of the transplanted kidney. The 59-year-old white male patient had received a cadaveric renal transplant at our clinic and returned 5 years later with proteinuria and elevated serum creatinine levels, consistent with nephrotic syndrome. We review the expression of Kidd antigens and the development and detection of Kidd antibodies, and discuss the case reports from the literature of Kidd antibodies associated with kidney-graft rejection that suggest Kidd antigens play a role as a minor histocompatibility antigen.

Harvesting autologous stem cells from a patient with red blood cell abnormalities of ß-thalassemia intermedia.

BACKGROUND: Autologous stem cell transplants in patients with hemoglobinopathies are limited. Previous reports used granulocyte-colony-stimulating factor (G-CSF) for mobilization of stem cells; there are no reported cases undergoing plerixafor mobilization. We report such a patient, providing guidance for peripheral blood stem cells collection when aberrant red blood cells (RBCs) disrupt normal separation. STUDY DESIGN AND METHODS: A patient with ß-thalassemia intermedia and hereditary persistence of fetal hemoglobin presented for peripheral blood stem cell collection for autologous transplant for myeloma. He underwent splenectomy for anemia secondary to hemoglobinopathy and chemotherapy, ceasing RBC transfusions. The patient was mobilized using plerixafor after collection with G-CSF failed. RESULTS: Collections were performed using an apheresis system, processing 24 L daily. Peripheral blood and apheresis product CD34 determinations were performed daily. On Day 1, the product yield was 0.04 × 10(6) CD34 cells/kg, less than expected based on white blood cell count and CD34-positive cells. Peripheral blood smear showed nucleated RBCs and RBC morphologic abnormalities. Changes in instrument variables were made after consultation with Terumo BCT to adjust for variable distribution of mononuclear and stem cells during centrifugation. Collecting stem cells at a deeper location and centrifuging faster improved collection, and a cumulative total of 4.40 × 10(6) CD34 cells/kg was achieved after four collections. The patient underwent tandem autologous transplantation and engrafted within 12 to 13 days of each transplant. CONCLUSIONS: Adjustments in apheresis variables allowed successful collection of peripheral blood stem cells from a patient with RBC anomalies of ß-thalassemia that interfered with standard stem cell harvesting.

Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen-specific cellular immunity.

Patients with multiple myeloma (MM) undergoing high dose therapy and autologous stem cell transplantation (SCT) remain at risk for disease progression. Induction of the expression of highly immunogenic cancer testis antigens (CTA) in malignant plasma cells in MM patients may trigger a protective immune response following SCT. We initiated a phase II clinical trial of the DNA hypomethylating agent, azacitidine (Aza) administered sequentially with lenalidomide (Rev) in patients with MM. Three cycles of Aza and Rev were administered and autologous lymphocytes were collected following the 2nd and 3rd cycles of Aza-Rev and cryopreserved. Subsequent stem cell mobilization was followed by high-dose melphalan and SCT. Autologous lymphocyte infusion (ALI) was performed in the second month following transplantation. Fourteen patients have completed the investigational therapy; autologous lymphocytes were collected from all of the patients. Thirteen patients have successfully completed SCT and 11 have undergone ALI. Six patients tested have demonstrated CTA up-regulation in either unfractionated bone marrow (n = 4) or CD138+ cells (n = 2). CTA (CTAG1B)-specific T cell response has been observed in all three patients tested and persists following SCT. Epigenetic induction of an adaptive immune response to cancer testis antigens is safe and feasible in MM patients undergoing SCT.

Extracorporeal photopheresis: clinical use so far.

Extracorporeal photopheresis (ECP or photopheresis) is an advanced therapeutic apheresis procedure in which blood is separated into its various components and the isolated buffy coat is treated with 8-methoxypsoralen (a photoactivating drug), exposed to ultraviolet light and returned to the patient. All other remaining blood components are also returned to the patient. The purpose of this procedure is immunomodulation. The treated leukocytes, specifically T-cells, are returned to the patient's circulation and will induce cytotoxicity and reduce proliferation of new T-cells. In the United States, ECP was initially approved for the treatment of cutaneous T-cell lymphoma by the US Food and Drug Administration in the late 1980s. Since that time, it has been used as an "off-label" therapy to treat several other autoimmune diseases in the United States and even more extensively in Europe and Asia. The following review is limited to the current clinical use of ECP in cutaneous T-cell lymphoma, Crohn's disease, systemic sclerosis, graft versus host disease, and emerging data on nephrogenic systemic fibrosis.

Therapeutic apheresis in critically ill patients.

Therapeutic apheresis procedures in critically ill patients comprises of therapeutic plasma exchange in most cases but also less commonly, erythrocytapheresis (red cell exchange), thrombocytapheresis, or leukocytapheresis. These procedures present a number of challenges to the apheresis healthcare team, and there are myriad beneficial and adverse effects for patients. In this patient population, one has to weigh the risks against the benefits and especially in those situations where apheresis is requested as a treatment when other alternative therapies have failed. Therapeutic plasma exchange is capable of removing toxins, pathologic auto- and allo-antibodies but will also remove beneficial medications, clotting factors and cations which are chelated by citrate anticoagulant. Herein, we review clinically significant issues that are commonly encountered in patients that are in the intensive care unit and have conditions that require therapeutic apheresis.

Investigation of heparin-related hypotensive adverse events during photopheresis: utility of a patient care database.

BACKGROUND: Extracorporeal photopheresis (ECP) is a procedure in which leukocytes are harvested from a patient's whole blood, treated with a DNA binding dye and ultraviolet light to inactivate lymphocytes, and then returned into the patient's circulation. In January 2008, we observed moderately severe anaphylactoid reactions in eight of 16 patients undergoing ECP. CASE STUDY: Each affected individual exhibited hypotension of sudden onset, usually with tachycardia, during the return of heparin-anticoagulated blood at the end of the first cycle of collection of leukocytes. A systematic investigation of possible contributing factors revealed that all reactions were associated with administration of a single new lot of heparin. RESULTS: Changing to a different manufacturer of heparin eliminated the occurrence of further such hypotensive reactions during ECP. Although the symptoms were initially attributed to vasovagal reactions or dehydration, their temporal association with exposure to a new lot of heparin suggested a procedure-related phenomenon. Of particular note, was the finding that of the eight patients who had reactions at any time, six had initial exposures without reactions, suggesting a process of sensitization. CONCLUSION: This study demonstrated the value of a patient database listing lot numbers of all medications and components used in each routine ECP procedure for facilitating rapid determination of common patient exposures, making it easier to determine the cause of adverse events, in this case, a particular lot of heparin responsible for the hypotensive adverse events.

Fecal occult blood testing.

Colorectal cancer (CRC) is the third most common cancer in the United States. A reduction in cumulative mortality occurs when patients are routinely screened by fecal occult blood tests (FOBT) and early lesions are removed. These point-of-care tests detect minute amounts of blood released from precancerous and cancerous colon lesions. Positive test results should be followed up with complete diagnostic testing to treat precancerous lesions and diagnose patients at earlier stages of cancer, thereby increasing overall survival. More complex assays are designed to detect genetic changes in cells released from malignant and even premalignant lesions. This article provides information on the screening and diagnostic tests available for CRC detection as well as the advantages and disadvantages of each.