Acute Kidney Injury During Hospitalization Increases the Risk of VTE.

BACKGROUND: Kidney disease has been linked to risk for hospitalization-related (HR) VTE, but the effect size and differences across types of kidney disease are described poorly. RESEARCH QUESTION: Can the risk for HR VTE among patients with acute kidney injury (AKI) and chronic kidney disease be quantified, and if so, how? STUDY DESIGN AND METHODS: We prospectively collected data on hospitalized adult patients and documented HR VTE events. We recorded creatinine clearance (CrCl) daily throughout hospitalization and modeled the effects that admission CrCl, peak CrCl, average CrCl, and AKI had on HR VTE. We controlled for known VTE risk factors and daily administration of chemoprophylaxis. RESULTS: Of the 6,552 admissions that met our inclusion criteria, 184 (2.81%) patients experienced an HR VTE. Surgery, AKI, chemical prophylaxis, and admission albumin all were associated with HR VTE in univariate analysis, but neither admission CrCl nor average CrCl (throughout the hospitalization) increased the odds of HR VTE. Kaplan-Meier curves showed AKI, whether it occurred before or during the hospitalization, was associated significantly with time to HR VTE. Cox regression analysis found that AKI was associated independently with HR VTE, as was surgery during admission, enoxaparin dose, and admission albumin. Sensitivity analyses showed that AKI lost significance when only patients with traumatic injuries were assessed. INTERPRETATION: We found that AKI increases the risk for HR VTE in a large, heterogeneous population that included medical and surgical patients. However, this relationship was not seen in patients with traumatic injuries.

The clinical efficacy of pentoxifylline and l-glutamine on ischemia and reperfusion injury in cattle with displaced abomasum: a longitudinal study.

This study aimed to assess the clinical efficacy of pentoxifylline (PTX) and L-glutamine (L-Gln) treatment on ischemia and reperfusion (I/R) injury in the abomasal tissue, acute phase response (APR), oxidative stress (OS), cytokine response, hemostatic, and coagulation disorders in the 96-h period before and after surgery in displaced abomasum (DA) cases. The study sample consisted of 48 dairy cows with DA that were categorized into four groups as group S (Sham group) (9 Left displaced abomasum (LDA)+3 Right displaced abomasum (RDA), group P (PTX) (10 LDA+2 RDA), group G (L-Gln) (10 LDA+2 RDA), and group P+G (PTX+L-Gln) (10 LDA+2 RDA). Acute-phase protein (Haptoglobin), oxidative stress indicators (malondialdehyde, nitric oxide, and glutathione), cytokines (tumor necrosis factor (TNF)-α and interleukin-1ß (IL-1ß), coagulation factors (D-Dimer, Antithrombin (ATIII), Thrombin-antithrombin complex, Plasminogen activator inhibitor-1), and enzyme activities (lactate dehydrogenase, gamma- -glutamyl transferase, sorbitol dehydrogenase, glutamate dehydrogenase, adenosine deaminase, myeloperoxidase, and creatine phosphokinase) in blood serum samples and coagulometric analyses of blood plasma were performed in samples taken before the operation and at 30 and 60 min and 2, 5, 10, 24, 48, 72, and 96 h after the operation. In DA cases, while post-operative treatment procedures with PTX and L-Gln were effective in decreasing APR and OS, these were ineffective in prohibiting the inflammatory response coordinated by cytokines. For the treatment and prevention of I/R injury in the DA cases, PTX and L-Gln procedures hold promise with their effects on APR, OS, and hemostatic dysfunction. Additional treatment procedures are required for the suppression of inflammatory response, and the effectiveness of preconditioning treatment may be evaluated.

The evaluation of hemostatic dysfunction and disseminated intravascular coagulation in dairy cows with abomasal displacement.

Disseminated intravascular coagulation (DIC) is a complex, dynamic and hemostatic disorder which develops secondarily to a disease characterized with an imbalance in the pro-coagulant and anti-coagulant components of hemostasis. The aim of the study is to evaluate hemostatic dysfunc- tion and the DIC syndrome in cattle with displaced abomasum (DA), with using the hematologic analyses and an extensive coagulation profile in the 96 hour-period including before and after surgery. The animal material of the study consisted of 12 dairy cows diagnosed with displaced abomasum (9 LDA and 3 RDA without volvulus) in the 2-4 week period after parturation and with no other post-partum disease. In dairy cows diagnosed with DA, hematological, coagulomet- ric (PT, APTT, Fibrinogen) and coagulation factor analyses [D-Dimer, TAT (thrombin-anti- thrombin complex), ATIII (antithrombin III), PAI-1 (plazminogen activator inhibitor-1] were performed in blood samples obtained before the operation as well as 30 minutes, 60 minutes and 2, 5, 10, 24, 48, 72 and 96 hours after the operation. In the DA cases, abnormalities were found in 6 of the 8 coagulation parameters. In the LDA and RDA groups, prolonged PT (sec), PT (INR) and APTT, hypofibrinogenemia, an increase in serum D-Dimer concentration at 72 and 96 hours after the operation and an increase in serum ATIII concentrations before and 30, 60 minutes and 2, 5, 72 and 96 hours after the operation was found (p⟨0.05). Hemostatic dysfunction and the risk of DIC developing in DA cases and continuing in the post-operative period was determined.

Effect of pentoxifylline on endotoxin-induced haemostatic disturbances in rabbits.

Pentoxifylline (PTX, a methylxanthine derivative) has been found to interrupt early gene activation for tumour necrosis factor, interleukin-1, interleukin-6 and tissue factor production and to improve survival from experimental sepsis. During endotoxaemia, lipopolysaccharide (LPS, endotoxin) and proinflammatory cytokines trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. The present study was undertaken to determine whether pentoxifylline could prevent coagulation disturbances in LPS-treated rabbits. Endotoxaemia was induced with E. coli lipopolysaccharide in New Zealand White rabbits. Forty rabbits were used and divided into four equal groups. Group 1 served as a control group; Group 2: lipopolysaccharide was injected intravenously, Group 3: pentoxifylline was injected intraperitoneally, Group 4: lipopolysaccharide and pentoxifylline were injected simultaneously. Blood samples were collected 6 h after the treatments. In rabbits with endotoxin-induced DIC, platelet count, leukocyte count, percentage of differential leukocyte values, fibrinogen level, antithrombin III (AT-III) and protein C (PC) activity were decreased. Moreover, activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged when compared to the control group. In conclusion, haemostatic disturbances associated with endotoxin-induced DIC were moderately suppressed by the administration of PTX.

How a New York cardiac surgery program uses outcomes data.

In New York State, a risk-adjusted outcomes system has been used by the Department of Health to monitor all cardiac operations since January 1989. Hospital-specific and physician-specific results are published annually. In this report we describe the experience of one hospital in New York State whose results showed a higher than expected surgical mortality. Staff reactions were initially skeptical, and case reviews found no quality-of-care problems. However, a different approach using statistical analysis of the detailed case-specific outcomes data was more revealing. The excess mortality was localized to patients having high-acuity, emergency coronary artery bypass grafting, particularly those who had suffered a preoperative acute myocardial infarction less than 6 hours before, those who were in shock, or those who were in a hemodynamically unstable condition. The staff responded with a focused effort to optimize the management of these patients, resulting in zero mortality for emergency coronary artery bypass grafting during the following year. In the process, staff from all departments joined together in a more collaborative approach to the cardiac surgery program. Outcomes data can be useful for effecting program improvement if comparable norms and open access for flexible analysis are available.

Alternative conduits for coronary revascularization: a novel approach for harvest of the lesser saphenous vein.

Previous use of the greater saphenous vein limits the subsequent availability of conduit for coronary artery bypass grafting (CABG). One readily available alternative conduit is the lesser saphenous vein (LSV). During a 4-year period, 34 LSVs were explored in 23 patients using a novel surgical approach. The incision used for LSV harvest was carried through and deep into the muscular fascia, posterior to the tibia, along the length of the leg, developing a fascial-cutaneous flap. The LSV in all patients was imaged before operation by venous duplex scanning. Important anatomic details were mapped on the patient's leg before surgery using indelible ink. Findings at operation correlated well with the duplex imaging results. Of the 34 LSVs explored 31 were judged usable by the operating surgeon. In eight patients bilateral LSVs were used and in two this vein was the only conduit available. Among patients undergoing LSV harvest there was no operative mortality and minimal operative morbidity related to harvesting. Only one wound infection developed at the incision site. There were no documented cases of deep vein thrombosis. A case-control study was performed in which a control group of 25 patients undergoing CABG without use of the LSV were compared with the 23 who had LSVs harvested; patients in both groups underwent preoperative venous duplex studies. There were no significant differences in operative mortality or morbidity rate between groups (statistical power > 0.8 for these negative observations), suggesting that harvest of the LSV is usually successful when used in conjunction with preoperative venous duplex scanning.(ABSTRACT TRUNCATED AT 250 WORDS)

Porins and lipopolysaccharide stimulate platelet activating factor synthesis by human mesangial cells.

Porins, a family of hydrophobic proteins located in the outer membrane of the cell wall of gram-negative bacteria and lipopolysaccharide (LPS), were shown to stimulate the synthesis of platelet activating factor (PAF), a phospholipid mediator of inflammation and endotoxic shock, by cultured human glomerular mesangial cells (MC). The synthesis of PAF induced by porins was rapid (peak at 20 min) and independent either from contamination by LPS or from generation of an endotoxin-induced cytokine such as tumor necrosis factor (TNF) since it was not prevented by cycloheximide, an inhibitor of protein synthesis or anti-TNF blocking antibodies. LPS also stimulated PAF synthesis by MC. However, the kinetic of PAF synthesis induced by LPS was biphasic with an early and transient peak at 10 minutes and a second and sustained peak at three to six hours. This second peak required an intact protein synthesis and was prevented by anti-TNF antibodies, suggesting the dependency on LPS-induced synthesis of TNF. Experiments with labeled precursors demonstrated that in MC, either after stimulation with porins or LPS, PAF was synthesized via the remodeling pathway that involves acetylation of 1-0-alkyl-sn-glyceryl-3-phosphorylcholine (2-lyso-PAF) generated from 1-0-alkyl-2-acyl-sn-glyceryl-3-phosphorylcholine by phospholipase A2 (PLA2) activity. Porins and LPS, indeed, induced PLA2-dependent mobilization of [14C]-arachidonic acid that was inhibited by p-bromodiphenacylbromide (PBDB). PBDB, an inhibitor of PLA2, also blocked PAF synthesis by preventing the mobilization of 2-lyso-PAF, the substrate for PAF-specific acetyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)

Platelet-activating factor in bronchoalveolar lavage from patients with sarcoidosis.

Platelet-activating factor (PAF), a lipid mediator of inflammation and anaphylaxis, may play a role in several physiopathologic alterations of the lung. A lipid compound with physicochemical and biologic characteristics similar to synthetic PAF was extracted and purified from bronchoalveolar lavage (BAL) fluid of 15 of 34 patients with sarcoidosis. PAF was quantitated by a bioassay on washed rabbit platelets. The specificity of platelet aggregation was assessed by using two different PAF receptor antagonists. The incidence of detectable amounts of PAF in BAL fluid of sarcoid patients was statistically significant (chi 2 = 4.064, p = 0.044) when compared with the 14 normal control subjects. The results demonstrated an increased production of PAF in the lower respiratory tract of patients with sarcoidosis. The presence of PAF in BAL fluid, however, did not correlate with radiologic stage, intensity of alveolitis, gallium scanning positivity, angiotensin-converting enzyme serum level, or lung function tests. Therefore, a direct relationship between presence of PAF in BAL fluid and activity of lung disease in patients with sarcoidosis was not directly established.

Donor-specific cytotoxicity testing: an advance in detecting pulmonary allograft rejection.

Ten beagle dogs underwent left unilateral lung transplantation and were treated with cyclosporine and azathioprine. After three days, cyclosporine administration was discontinued and azathioprine administration was maintained at a suboptimal dose to allow a graded response to the pulmonary allograft. Dogs were monitored by chest roentgenogram, bronchoalveolar lavage (BAL), and sampling of peripheral blood lymphocytes at weekly intervals. Open lung biopsies also were performed at weekly intervals in 5 of the dogs. Lymphocytes from the BAL and peripheral blood and those grown in culture from open and transbronchial biopsy specimens were tested for donor-specific cytotoxicity (DSC) by testing their responsiveness to lymphocytes from their donor. Rejection was confirmed in all animals. Donor-specific cytotoxicity became detectable in all animals in either the BAL fluid or biopsy specimens. An abnormal chest roentgenogram developed in 9 dogs, but not until after DSC was detected in the BAL in 7. In the open biopsy specimens tested for DSC, all exhibited DSC synchronous with the first changes noted on chest roentgenogram. Donor-specific cytotoxicity was sensitive for detecting rejection in 8 of 9 dogs in the BAL and in 5 of 5 dogs in the open biopsy specimens. Based on these results, 3 additional dogs were maintained on cyclosporine. Two of these dogs did not reject their transplants and had no evidence of DSC. We conclude that donor-specific functional assays provide an advance over less sensitive clinical techniques.