Bariatric Surgery for Congestive Heart Failure Patients Improves Access to Transplantation and Long-term Survival.

INTRODUCTION: Obese patients with congestive heart failure (CHF) are often denied access to heart transplantation until they obtain significant weight loss to achieve a certain BMI threshold, often less than 35 kg/m2. It is unknown whether the rapid weight loss associated with bariatric surgery leads to improved waitlist placement, and as such improved survival for morbidly obese patients with CHF. METHODS: A decision analytic Markov state transition model was created to simulate the life of morbidly obese patients with CHF who were deemed ineligible to be waitlisted for heart transplantation unless they achieved a BMI less than 35 kg/m2. Life expectancy following medical weight management (MWM), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG) was estimated. Base case patients were defined as having a pre-intervention BMI of 45 kg/m2. Sensitivity analysis of initial BMI was performed. Markov parameters were extracted from literature review. RESULTS: RYGB improved survival compared with both SG and MWM. RYGB patients had higher rates of transplantation, leading to improved mean long-term survival. Base case patients who underwent RYGB gained 2.1 additional years of life compared with patient's who underwent SG and 7.4 additional years of life compared with MWM. SG patients gained 5.3 years of life compared with MWM. CONCLUSIONS: When strict waitlist criteria were applied, bariatric surgery improved access to heart transplantation and thereby increased long-term survival compared with MWM. Morbidly obese CHF patients who anticipate need for heart transplantation should be encouraged to pursue surgical weight management strategies, necessitating discussion between bariatric surgeons, cardiologists, and cardiac surgeons for appropriate perioperative risk management.

Viscoelastic measurements of platelet function, not fibrinogen function, predicts sensitivity to tissue-type plasminogen activator in trauma patients.

BACKGROUND: Systemic hyperfibrinolysis is a lethal phenotype of trauma-induced coagulopathy. Its pathogenesis is poorly understood. Recent studies have support a central role of platelets in hemostasis and in fibrinolysis regulation, implying that platelet impairment is integral to the development of postinjury systemic hyperfibrinolysis. OBJECTIVE: The objective of this study was to identify if platelet function is associated with blood clot sensitivity to fibrinolysis. We hypothesize that platelet impairment of the ADP pathway correlates with fibrinolysis sensitivity in trauma patients. METHODS: A prospective observational study of patients meeting the criteria for the highest level of activation at an urban trauma center was performed. Viscoelastic parameters associated with platelet function (maximum amplitude [MA]) were measured with native thrombelastography (TEG), and TEG platelet mapping of the ADP pathway (ADP-MA). The contribution of fibrinogen to clotting was measured with TEG (angle) and the TEG functional fibrinogen (FF) assay (FF-MA). Another TEG assay containing tissue-type plasminogen activator (t-PA) (75 ng mL(-1) ) was used to assess clot sensitivity to an exogenous fibrinolytic stimulus by use of the TEG lysis at 30 min (LY30) variable. Multivariate linear regression was used to identify which TEG variable correlated with t-PA-LY30 (quantification of fibrinolysis sensitivity). RESULTS: Fifty-eight trauma patients were included in the analysis, with a median injury severity score of 17 and a base deficit of 6 mEq L(-1) . TEG parameters that significantly predicted t-PA-LY30 were related to platelet function (ADP-MA, P = 0.001; MA, P < 0.001) but not to fibrinogen (FF-MA, P = 0.773; angle, P = 0.083). Clinical predictors of platelet ADP impairment included calcium level (P = 0.001), base deficit (P = 0.001), and injury severity (P = 0.001). RESULTS AND CONCLUSIONS: Platelet impairment of the ADP pathway is associated with increased sensitivity to t-PA. ADP pathway inhibition in platelets may be an early step in the pathogenesis of systemic hyperfibrinolysis.

Trauma-Induced Coagulopathy: An Institution's 35 Year Perspective on Practice and Research.

INTRODUCTION: Injury is the second leading cause of death worldwide, and as much as 40% of injury-related mortality is attributed to uncontrollable hemorrhage. This persists despite establishment of regionalized trauma systems and advances in the management of severely injured patients. Trauma-induced coagulopathy has been identified as the most common preventable cause of postinjury mortality. METHODS: A review of the current literature was performed by collecting PUBMED references related to trauma-induced coagulopathy. Data were then critically analyzed and summarized based on the authors' clinical and research perspective, as well as that reported by other institutions and researchers interested in trauma-induced coagulopathy. A particular focus was placed on those aspects of coagulopathy in which agreement among clinical and basic scientists is currently lacking; these include, pathophysiology, the role of blood components and factor therapy, and goal-directed assessment and management. RESULTS: Trauma-induced coagulopathy has been recognized in approximately one-third of trauma patients. There is a vast range of severity, and the emergence of viscoelastic assays, such as thrombelastography and rotational thromboelastogram, has refined its diagnosis and management, particularly through the establishment of goal-directed massive transfusion protocols. Despite advancements in the diagnosis and management of trauma-induced coagulopathy, much remains to be understood regarding its pathophysiology. The cell-based model of hemostasis has allowed for characterization of endothelial dysfunction, impaired thrombin generation, platelet dysfunction, fibrinolysis, endogenous anticoagulants such as protein-C, and antifibrinolytic proteins. These concepts collectively compose the contemporary, but still partial, understanding of trauma-induced coagulopathy. CONCLUSION: Trauma-induced coagulopathy is a complex pathophysiological condition, of which some mechanisms have been characterized, but much remains to be understood in order to translate this knowledge into improved outcomes for the injured patient.

Hypertonic saline activation of p38 MAPK primes the PMN respiratory burst.

Investigation of hypertonic saline (HTS) modulation of neutrophils (PMN) cytotoxic responses has generated seemingly contradictory results. Clinically relevant levels of HTS attenuate receptor-mediated p38 MAPK signaling, whereas higher levels activate p38 MAPK. Concurrently, HTS exerts a dose-dependent attenuation of the PMN respiratory burst, most notably at concentrations where p38 MAPK is activated. We hypothesized that HTS-mediated p38 MAPK activation augments the PMN respiratory burst on return to normotonicity. We found that although clinically relevant levels of HTS (Na+ > or = 200 mM) did not activate p38 MAPK, higher concentrations (Na+ > or = 300 mM) resulted in activation comparable with that after PAF stimulation. Transient stimulation with high levels of HTS primed the PMN respiratory burst in response to fMLP and PMA. This effect was attenuated by pretreatment with SB 203580, a p38 MAPK specific inhibitor. We conclude that severe osmotic shock primes the respiratory burst via p38 MAPK signaling, further supporting the role of this signaling cascade in PMN priming.

Isolation of Mobiluncus species from clinical specimens by using cold enrichment and selective media.

New and selective Rlk and SA media, combined with cold enrichment at 4 to 5 degrees C, allowed isolation of Mobiluncus species from patients with bacterial vaginosis at higher rates than with conventional cultivation methods. Rlk medium consists of Columbia CNA agar supplemented with peptone, yeast extract, 5% laked rabbit or sheep blood, nalidixic acid, and tinidazole. SA medium consists of Columbia CNA agar supplemented with 2% rabbit serum, 1.6% laked rabbit or sheep blood, nalidixic acid, and tinidazole. Use of these selective media plus the cold enrichment technique permitted Mobiluncus species to propagate at rates similar to those of other anaerobic members of the vaginal flora.

Comparison of three procedures for biochemical testing of anaerobic bacteria.

The Analytab Products, Inc. (API), anaerobic multitest microsystem (MICRO) was compared with the Center for Disease Control conventional (CONV) thioglycolate (supplemented with hemin and vitamin K1) system and with pre-reduced anaerobically sterilized (PRAS) media as recommended by the Virginia Polytechnic Institute. Growth from a solid medium was suspended to produce standard inocula. Substrates included 16 carbohydrates, indole, urea, gelatin, and esculin. API strips were inoculated in air and incubated in GasPak (BBL) jars. MICRO tests were read at 1 and 2 days. CONV tests at 1, 2, and 7 days, and PRAS tests at 3 weeks. One hundred thirty well-characterized strains of anaerobes (76 gram-negative rods, 16 cocci, 26 gram-positive nonsporeforming rods, and 12 clostridia), including 48 reference strains, were studied. Of 2,600 tests performed, 2,085 (80.2%) showed agreement with all three methods. There was 90.9% agreement between the MICRO and CONV, 84.9% between the MICRO and PRAS, and 84.6% between the CONV and PRAS tests. All MICRO tests were reliable except for indole, which was not sensitive enough, and gelatin, which was very insensitive. The MICRO system permits performance of biochemical tests at the workbench in the average clinical laboratory without the need for expensive equipment and time-consuming procedures.