A case report of transfusion-related acute lung injury during plasma exchange therapy for thrombotic thrombocytopenia purpura

Transfusion-related acute lung injury (TRALI) is a transfusion reaction that is often under recognized and underreported. Implications for diagnosis not only influence treatment considerations but also extend to donor selection, donor deferral and ultimately the safety of the final blood product. We report a case of a previously well 19-year-old female who presented a one week history of flu-like symptoms and mucosal bleeding. Laboratory results confirmed the diagnosis of thrombotic thrombocytopaenia purpura (TTP) and she was commenced on plasma exchange. During her second day of plasma exchange, she developed dyspnoea and rigors. Examination and investigation findings were consistent with a clinical diagnosis of TRALI. Granulocytes immunofluorescent test (GIFT - flow cytometry) was performed and cross reactivity was demonstrated between the patient's granulocytes and plasma from one of the nine donor fresh frozen plasma (FFP) packs. She made a full recovery. TRALIa accounts for 7% of all adverse events reported in the Serious Hazards of Transfusion (SHOT) database and has a mortality rate between 5-25%. Apheresis patients are a particularly vulnerable group of patients where clinical recognition and rapid laboratory confirmation of TRALI is imperative to minimize the risk of further patient exposure to donor granulocyte or human leukocyte antigen (HLA) antibodies. The provision of plasma from male donors may additionally reduce exposure. On a wider scale, rapid donor identification and deferral maintains the safety of the national blood supply.     

Systematic Coronary Risk Evaluation (SCORE): JACC Focus Seminar 4/8

Clinical estimation of the combined effect of several risk factors is unreliable and this resulted in the development of a number of risk estimation systems to guide clinical practice. Here, after defining general principles of risk estimation, the authors describe the evolution of the European Society of Cardiology’s (ESC) Systematic COronary Risk Evaluation (SCORE) risk estimation system and some learnings from the data. They move on to describe the establishment of the ESC’s Cardiovascular Risk Collaboration and outline its proposed research directions. First among these is the evolution of SCORE 2, which provides updated, calibrated risk estimates for total cardiovascular events for low, moderate, high, and very high-risk regions of Europe. The authors conclude by considering that the future of risk estimation may be to express risk as years of exposure to a cardiovascular risk factor profile rather than risk over a fixed time period, such as 10 years, and how advances in genetics may permit individualized lifetime risk estimation from childhood on.     

Insulin-like growth factor-binding protein-1 modulates blood glucose levels.

We have determined the consequences of insulin-like growth factor-binding protein-1 (IGFBP-1) administration alone and in combination with insulin-like growth factor-I (IGF-I). Human recombinant IGF-I, infused as a bolus into male Wistar rats, induced a fall in plasma glucose to 72 +/- 3% of baseline 15 min after injection. Co-infusion of equimolar concentrations of human IGFBP-1 abolished the IGF-I-induced fall (P less than 0.001). Injection of IGFBP-1 alone caused a rise in plasma glucose levels (P less than 0.002). The half life of human IGFBP-1, measured using a primate-specific RIA, was 12.5 +/- 0.7 min and was not influenced by the co-infusion of IGF-I. This study demonstrates that, in the rat, human IGFBP-1 blocks the hypoglycemic response to intravenous IGF-I and increases blood glucose levels when administered alone. Since IGFBP-1 concentrations are dependent on metabolic status, we suggest that fluctuating IGFBP-1 levels might modulate the hypoglycemic activity of unbound IGFs in the circulation.     

Cervical Spine Motion During Football Equipment-Removal Protocols: A Challenge to the All-or-Nothing Endeavor

Context

The National Athletic Trainers'' Association position statement on acute management of the cervical spine-injured athlete recommended the all-or-nothing endeavor, which involves removing or not removing both helmet and shoulder pads, from equipment-laden American football and ice hockey athletes. However, in supporting research, investigators have not considered alternative protocols.

Objective

To measure cervical spine movement (head relative to sternum) produced when certified athletic trainers (ATs) use the all-or-nothing endeavor and to compare these findings with the movement produced using an alternative pack-and-fill protocol, which involves packing the area under and around the cervical neck and head with rolled towels.

Design

Crossover study.

Setting

Movement analysis laboratory.

Patients or Other Participants

Eight male collegiate football players (age = 21.4 ± 1.4 years; height = 1.87 ± 0.02 m; mass = 103.6 ± 12.5 kg).

Intervention(s)

Four ATs removed equipment under 4 conditions: removal of helmet only followed by placing the head on the ground (H), removal of the helmet only followed by pack-and-fill (HP), removal of the helmet and shoulder pads followed by placing the head on the ground (HS), and removal of the helmet and shoulder pads followed by pack-and-fill (HSP). Motion capture was used to track the movement of the head with respect to the sternum during equipment removal.

Main Outcome Measure(s)

We measured head movement relative to sternum movement (translations and rotations). We used 4 × 4 analyses of variance with repeated measures to compare discrete motion variables (changes in position and total excursions) among protocols and ATs.

Results

Protocol HP resulted in a 0.1 ± 0.6 cm rise in head position compared with a 1.4 ± 0.3 cm drop with protocol HS (P < .001). Protocol HP produced 4.9° less total angular excursion (P < .001) and 2.1 cm less total vertical excursion (P < .001) than protocol HS.

Conclusions

The pack-and-fill protocol was more effective than shoulder pad removal in minimizing cervical spine movement throughout the equipment-removal process. This study provides evidence for including the pack-and-fill protocol in future treatment recommendations when helmet removal is necessary for on-field care.Key Words: National Athletic Trainers'' Association position statement, pack and fill, motion analysis, helmet removal

Key Points

• The pack-and-fill protocol resulted in less overall motion than removal of the helmet and shoulder pads followed by placing the head on the ground, which is currently endorsed by the National Athletic Trainers'' Association.
• Using pack and fill, the athletic trainers could position the head at release in, on average, nearly the identical position as at initiation.
• Removal of the helmet and shoulder pads resulted in a drop in linear and angular head position, placing the cervical spine into increased extension.

American football has the highest number of catastrophic cervical spine injuries of all sports in the United States.¹ Although still of major concern, the incidence of catastrophic cervical spine injuries has declined over the past 35 years, and the rate is now less than 1 per 100 000 exposures.² Much of this decline has been attributed to a 1976 rule change making it illegal to spear, or lower the head to butt or ram an opponent.² Given the force applied at the front and top of a player''s helmet, spearing has long been associated with the axial-load mechanism of injury that results in catastrophic cervical spine injury.³ However, despite a focus on player safety, researchers^4–6 have suggested that the incidence of spearing or other axial head impacts may be as prevalent in American football in the United States today as before the 1976 rule change. Instead, improved prehospital care and on-field management of equipment-laden athletes with potential spine injuries possibly also has led to a reduction in catastrophic cervical spine injuries by reducing the number of cervical spine injuries that result in catastrophic outcomes. This possibility needs to be documented, and research pertaining to prehospital care protocols and management techniques that may affect catastrophic spinal cord injury outcomes in American football needs to continue.Proper prehospital on-field medical care of the athlete with a spine injury, including equipment management, may be critical in limiting secondary cervical spine injury while also allowing access to the airway and chest compressions. The National Athletic Trainers'' Association (NATA) position statement on the acute management of the cervical spine-injured athlete⁷ includes the all-or–nothing technique, which discourages independent removal of the helmet or shoulder pads in American football or ice hockey when an athlete has a potential cervical spine injury. This specific NATA recommendation is based on several studies^8–11 in which the researchers measured vertebral positioning or spinal cord space before and after equipment removal and showed that when the football helmet is removed while the shoulder pads remain in place, cervical alignment can be compromised as the head and neck fall backward into extension.However, a gap exists in the body of evidence used to support this recommendation, as no authors of supporting studies have addressed the use of fillers (eg, rolled towels) to stabilize the head and cervical spine after removing only the helmet and leaving the shoulder pads on the athlete. This technique, termed pack and fill, would fill the void of the missing helmet by placing rolled towels around and beneath the posterior head, cervical spine, and surface of the spine board or ground to prevent the head and cervical spine from moving into extension during performance of critical-care tasks. Although the NATA position statement⁷ mentions this technique as a possibility for an athlete whose helmet is dislodged or shoulder pads are not removed easily, pack and fill could be an alternative clinical practice when removal of the helmet is necessary to provide safe access to the airway (eg, inability to remove the facemask efficiently or a poorly fitted football helmet creating instability of the head and cervical spine within the helmet). Decoster et al¹² recently demonstrated that pack and fill can effectively maintain a neutral sagittal cervical alignment after helmet removal.Another gap in these supporting studies is that they were based on static imaging and, therefore, did not account for the amount of head and neck movement that occurs during the equipment-removal process. In the case of shoulder-pad removal, this could be substantial. Therefore, the purposes of our study were to address these 2 gaps by measuring cervical spine movement (head with respect to sternum) throughout the removal process and to compare this movement among several possible removal protocols. We hypothesized that removal of the helmet combined with the pack-and-fill technique would result in less overall movement than removal of both the helmet and shoulder pads.     

Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis

Phenotype-driven approaches to gene discovery using inbred mice have been instrumental in identifying genetic determinants of inherited blood dyscrasias. The recessive mutant scat (severe combined anemia and thrombocytopenia) alternates between crisis and remission episodes, indicating an aberrant regulatory feedback mechanism common to erythrocyte and platelet formation. Here, we identify a missense mutation (G125V) in the scat Rasa3 gene, encoding a Ras GTPase activating protein (RasGAP), and elucidate the mechanism producing crisis episodes. The mutation causes mislocalization of RASA3 to the cytosol in scat red cells where it is inactive, leading to increased GTP-bound Ras. Erythropoiesis is severely blocked in scat crisis mice, and ~94% succumb during the second crisis (~30 d of age) from catastrophic hematopoietic failure in the spleen and bone marrow. Megakaryopoiesis is also defective during crisis. Notably, the scat phenotype is recapitulated in zebrafish when rasa3 is silenced. These results highlight a critical, conserved, and nonredundant role for RASA3 in vertebrate hematopoiesis.     

Prediagnostic circulating carotenoid levels and the risk of non-Hodgkin lymphoma: the Multiethnic Cohort

This analysis examined the association of non-Hodgkin lymphoma (NHL) with prediagnostic carotenoid levels, a marker for a diet rich in fruits and vegetables. We conducted a nested case-control study within the Multiethnic Cohort with 271 NHL cases and 538 controls matched on sex, ethnicity, location (Hawaii or Los Angeles), birth year, date and time of blood draw, and hours fasting before blood draw. Serum carotenoid levels were obtained by high-pressure liquid chromatography with photodiode array detection. Conditional logistic regression was used to calculate odds ratios (ORs) according to tertiles of serum carotenoids and trend tests using continuous variables. Higher total serum carotenoids (OR(T3 vs T1) = 0.66 [0.46-0.96]; P(trend) = .02), lycopene (OR = 0.54 [0.38-0.78]; P(trend) = .003), and α-cryptoxanthin (OR = 0.53 [0.36-0.78]; P(trend) = .003) were associated with a lower risk of NHL. For retinol (OR = 0.90 [0.61-1.33]; P(trend) = .04), a statistically significant inverse linear trend was detected. Risk estimates remained unchanged with adjustment for NHL risk factors and were similar in analyses stratified by sex and ethnicity; heterogeneity with NHL subtype was detected only for β-carotene. Other carotenoids, including α-carotene, β-carotene, lutein, β-cryptoxanthin, and zeaxanthin, showed no association with risk. These data provide support for a protective role of carotenoid-rich fruits and vegetables in the etiology of NHL.     

Renal cell carcinoma metastases to gallbladder

A 74-year old man underwent a radical cholecystectomy for presumed gallbladder cancer. The histology of the resected specimen in fact revealed the lesion to be metastatic renal cell carcinoma from his resected right nephrectomy performed 14 years previously.