Relationship between Obesity and Massive Transfusion Needs in Trauma Patients, and Validation of TASH Score in Obese Population: A Retrospective Study on 910 Trauma Patients.

BACKGROUND: Prediction of massive transfusion (MT) is challenging in management of trauma patients. However, MT and its prediction were poorly studied in obese patients. The main objective was to assess the relationship between obesity and MT needs in trauma patients. The secondary objectives were to validate the Trauma Associated Severe Hemorrhage (TASH) score in predicting MT in obese patients and to use a grey zone approach to optimize its ability to predict MT. METHODS AND FINDINGS: An observational retrospective study was conducted in a Level I Regional Trauma Center Trauma in obese and non-obese patients. MT was defined as ≥10 U of packed red blood cells in the first 24h and obesity as a BMI≥30 kg/m². Between January 2008 and December 2012, 119 obese and 791 non-obese trauma patients were included. The rate of MT was 10% (94/910) in the whole population. The MT rate tended to be higher in obese patients than in non-obese patients: 15% (18/119, 95%CI 9‒23%) versus 10% (76/791, 95%CI 8‒12%), OR, 1.68 [95%CI 0.97‒2.92], p = 0.07. After adjusting for Injury Severity Score (ISS), obesity was significantly associated with MT rate (OR, 1.79[95%CI 1.00‒3.21], p = 0.049). The TASH score was higher in the obese group than in the non-obese group: 7(4-11) versus 5(2-10) (p<0.001). The area under the ROC curves of the TASH score in predicting MT was very high and comparable between the obese and non-obese groups: 0.93 (95%CI, 0.89‒0.98) and 0.94 (95%CI, 0.92‒0.96), respectively (p = 0.80). The grey zone ranged respectively from 10 to 13 and from 9 to 12 in obese and non obese patients, and allowed separating patients at low, intermediate or high risk of MT using the TASH score. CONCLUSIONS: Obesity was associated with a higher rate of MT in trauma patients. The predictive performance of the TASH score and the grey zones were robust and comparable between obese and non-obese patients.

A simple assessment of haemothoraces thickness predicts abundant transfusion: a series of 525 blunt trauma patients.

BACKGROUND: The goal of this study was to evaluate the performance of haemothorax quantification to predict an abundant transfusion in blunt thoracic trauma patients. METHODS: This study included all severe trauma patients admitted into our trauma centre from January 2005 to January 2010, who presented a blunt thoracic trauma (thoracic AIS ≥1) and had a CT scan within the first hour following admission. For each haemothorax, thickness of dominant side and the cumulated thicknesses of both sides (Dominant-t, Cumulated-t), as well as lengths (Dominant-l, Cumulated-l) and the calculated volumes (Dominant-v, Cumulated-v provided by a previously validated formula) were retrospectively measured by CT scan. A multiple logistic regression was performed to define the independent risk factors for an abundant transfusion (≥5 packed red blood cells in the first 24h). Finally, ROC curves have been drawn on an isolated thoracic trauma subgroup to predict abundant transfusion. The more specific cut-offs were extracted from this analysis. RESULTS: From the 525 blunt thoracic trauma patients (75% males, mean age 38.2 (SD18.7) years, mean ISS 22.5 (SD16.4)), 31% received an abundant transfusion. In multivariable analysis, Cumulated-t was significantly associated with an abundant transfusion (OR 1.3 [95% CI 1.1-1.4], P=0.002). In isolated thoracic trauma subgroup (n=251), the global abilities of different CT measurements to predict abundant transfusion were significantly comparable (AUCs 0.69-0.70). The more specific cut-offs were established at 28mm for Cumulated-t (specificity 92%, positive predictive value 47%) and at 24mm for Dominant-t (specificity 92%; positive predictive value 43%). CONCLUSION: The haemothorax quantification upon admission may help to predict transfusion needs. Cumulated-t was found independent risk factor for abundant transfusion in a large population of severe trauma patients. Beyond a Cumulated-t of 28mm or a Dominant-t of 24mm, abundant transfusion will be very frequently necessary. LEVEL OF EVIDENCE: Retrospective review, level III.

Early coagulopathy at hospital admission predicts initial or delayed fibrinogen deficit in severe trauma patients.

BACKGROUND: Early detection of a fibrinogen deficit in the initial phase of trauma is a determinant for anticipating massive blood loss. Hemostatic impairment should rationally be associated with an overall depletion of clotting factors, leading to early coagulopathy. The main objective of this study was to evaluate whether the severity of coagulopathy at admission could predict an initial and delayed fibrinogen deficit during the initial management of severe trauma patients. METHODS: All severe trauma patients admitted consecutively to our trauma center between January 2006 and December 2009 were retrospectively reviewed. The results of coagulation tests and plasma fibrinogen levels at admission were studied. Patients were grouped according to severity of coagulopathy at admission: prothrombin time ratio and/or activated partial thromboplastin time ratio of 1.50 or greater, between 1.49 and 1.20, or less than 1.20. Correlation between severity of coagulopathy at admission and initial or delayed fibrinogen deficit (fibrinogen level < 1.5 g/L) within the first 24 hours was established. RESULTS: Of the 663 patients studied, 481 (72%) were male, and the mean (SD) Injury Severity Score (ISS) was 21.3 (17.6). At admission, 105 patients (20%) had severe coagulopathy, 215 (33%) had moderate coagulopathy, and 313 (47%) had no coagulopathy. The number of patients with a fibrinogen level less than 1.5 g/L at admission increased with the severity of coagulopathy: 87%, 29%, and 1%, respectively (p < 0.001). Corresponding rates for an initial fibrinogen level less than 1.0 g/L were 53%, 2%, 0.3%, respectively (p < 0.001). Moreover, severity of coagulopathy at admission was an independent risk factor of the occurrence of fibrinogen deficit within the first 24 hours (p < 0.001). CONCLUSION: Early coagulopathy at admission in severe trauma patients was strongly associated with a fibrinogen deficit during initial management. In the absence of specific monitoring of fibrinogen, coagulopathy severity helps to guide fibrinogen replacement therapy. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Hemoperitoneum semiquantitative analysis on admission of blunt trauma patients improves the prediction of massive transfusion.

BACKGROUND: The purpose of this study was to define whether the semiquantitative analysis of hemoperitoneum increases the accuracy of early prediction of massive transfusion (MT). METHODS: A retrospective review of severe trauma patients consecutively admitted to our trauma intensive care unit between January 2005 and December 2009 was conducted. Patients diagnosed with blunt abdominal trauma who had a computed tomography scan on admission were included. The hemoperitoneum size was defined using the Federle score on computed tomography as large, moderate, or minimal/none. The association between MT (≥10 U of packed red blood cells in the first 24 h) and moderate and large sizes of hemoperitoneum was assessed using a multiple logistic model. RESULTS: Of the 381 patients meeting the inclusion criteria, 270 (71%) were male; the mean age was 35.5 ± 18.2 years and mean injury severity score was 23.4 ± 17. Ninety-seven (26%) had large hemoperitoneum, 107 (28%) had moderate hemoperitoneum, and 177 (46%) had minimal/no hemoperitoneum. Eighty-three patients (22%) required MT. The positive predictive value for MT of a large hemoperitoneum was 41%, 23% for a moderate hemoperitoneum, and 10% for minimal/no hemoperitoneum (P < .001). The corresponding values for hypotensive patients were 61%, 32%, and 25%, respectively (P < .001). In the multivariate analysis model, only the large size of hemoperitoneum was significantly associated with MT (OR 6.4, 95% CI 2.9-14, P < .001, r(2) = 0.47). CONCLUSION: The assessment of the size of hemoperitoneum on admission substantially improves the prediction of MT in trauma patients and should be used to trigger and guide initial haemostatic resuscitation.

Increased plasma-immune cytokines throughout the high-dose melphalan-induced lymphodepletion in patients with multiple myeloma: a window for adoptive immunotherapy.

High-dose melphalan (HDM) followed by autologous stem cell transplantation (ASCT) is a standard treatment for patients with multiple myeloma. However, lymphocyte reconstitution is impaired after HDM. Recent work has suggested that the lymphopenia period occurring after various immunosuppressive or chemotherapy treatments may provide an interesting opportunity for adoptive antitumor immunotherapy. The objective of this study was to determine an immunotherapy window after HDM and ASCT, evaluating T cell lymphopenia, and measuring circulating immune cytokine concentrations in patients with multiple myeloma. The counts of T cell subpopulations reached a nadir at day 8 post-ASCT (day 10 post-HDM) and recovered by day 30. IL-6, IL-7, and IL-15 plasma levels increased on a median day 8 post-ASCT, respectively, 35-fold, 8-fold, and 10-fold compared with pre-HDM levels (p < or = 0.05). The increases in IL-7 and IL-15 levels were inversely correlated to the absolute lymphocyte count, unlike monocyte or myeloid counts. Furthermore, we have shown that CD3 T cells present in the ASC graft are activated, die rapidly when they are cultured without cytokine in vitro, and that addition of IL-7 or IL-15 could induce their survival and proliferation. In conclusion, the early lymphodepletion period, occurring 4-11 d post-HDM and ASCT, is associated with an increase of circulating immune cytokines and could be an optimal window to enhance the survival and proliferation of polyclonal T cells present in the ASC autograft and also of specific antimyeloma T cells previously expanded in vitro.

In vitro expansion of gamma delta T cells with anti-myeloma cell activity by Phosphostim and IL-2 in patients with multiple myeloma.

T-cell-mediated immunotherapy is a promising therapeutic option for multiple myeloma (MM). Gamma-delta T cells (gammadelta T cells) recognize phosphoantigens and display strong anti-tumour cytotoxicity. The synthetic agonist Phosphostim (bromohydrin pyrophosphate, BrHPP) has been shown to selectively activate Vgamma9Vdelta2 T cells. This study aimed to evaluate the expansion capacity and anti-myeloma cell cytotoxicity of circulating gammadelta T cells from MM patients at different time points throughout the disease, using Phosphostim and interleukin 2 (IL-2). Circulating gammadelta T cell counts in patients with newly diagnosed MM or in relapse did not differ from those in healthy donors. A 14-d culture of peripheral blood mononuclear cells with Phosphostim and IL-2 triggered a 100-fold expansion of gammadelta T cells in 78% of newly diagnosed patients. Gammadelta T cells harvested at the time of haematopoietic progenitor collection or in relapsing patients expanded less efficiently. Expanded gammadelta T cells killed 13/14 myeloma cell lines as well as primary myeloma cells, but not normal CD34 cells. Their killing efficiency was not affected by 2-d IL-2 starvation. This study demonstrated the ability of Phosphostim and IL-2 to expand gammadelta T cells from MM patients, and the efficient and stable killing of human myeloma cells by gd T cells.

Outcome and prognosis of severe thrombotic microangiopathies treated by plasma exchange.

BACKGROUND: Plasma exchange (PE) therapy has dramatically improved the outcome of thrombotic microangiopathies (TMA) in adults. However, resistance to PE, which indicates a poor prognosis, is observed in 1/3 of patients and remains not fully understood. We evaluated in this study the survival and the long-term outcome of severe TMA treated by PE and identified the predictive factors of resistance to PE and of mortality. MATERIAL/METHODS: Records of adults with severe TMA treated by PE were reviewed. Clinical and biological data, therapeutic delay to PE, plasma volume exchange per procedure, and number of PE sessions were collected. Mortality was assessed at one month and at one-year follow-up. All data were analyzed and compared between survived/deceased and between responder/non-responder patients. RESULTS: Nineteen females and six males were included. Mean age (+/-SD) was 46.8+/-16.3 years, Glasgow coma score 11+/-3, and Sequential Organ Failure Assessment (SOFA) score 5.8+/-2.8. Nineteen patients partially or fully responded to PE. Twenty patients were alive at one month and 19 at one year. The response to PE was the single discriminating parameter between survivors and non-survivors. A longer delay of PE and a neoplastic cause of TMA were significantly higher in the non-responders. CONCLUSIONS: Severe TMA treated by PE had a fair prognosis, with a survival rate at 76% after one year of follow-up. Unresponsiveness to PE was the only predictive factor of mortality; a neoplastic etiology of TMA and a longer therapeutic delay of PE were predictive of resistance to PE.

Functional regulatory T cells are collected in stem cell autografts by mobilization with high-dose cyclophosphamide and granulocyte colony-stimulating factor.

High-dose cyclophosphamide (Cy) and G-CSF are widely used to mobilize hemopoietic stem cells for treating patients with high-dose chemotherapy and autologous stem cell transplantation (ASCT). Because lymphocyte count in the graft collected after Cy-G-CSF treatment is an independent survival factor after ASCT for patients with multiple myeloma, our purpose was to study how Cy-G-CSF treatment affects the phenotype and function of T cells in patients with multiple myeloma. Cy induced a 3-fold decrease of T cell counts with a slow and partial T cell recovery of one-third at the time of hemopoietic stem cell collection. Cy-G-CSF treatment did not affect the relative ratios of central memory, effector memory, and late effector CD4+ or CD8+ T cells, but a decrease in the percentage of naive CD4+ cells was observed. The percentages of CD25+ cells increased 2- to 3-fold in CD4+ and CD8+ T cells, the former including both activated CD25low and CD25high cells. CD4+CD25high cells were regulatory T cells (Treg) that expressed high levels of FOXP3, CTLA-4, and GITR and displayed in vitro suppressive properties. The recovery of Treg absolute counts after Cy-G-CSF treatment was higher than the recovery of other lymphocyte subpopulations. In conclusion, Cy-G-CSF treatment induces a severe T cell count decrease without deleting Treg, which are potent inhibitors of antitumor response. The present data encourage novel therapeutic strategies to improve T cell recovery following ASCT while limiting Treg expansion.