Postoperative fibrinolytic resistance is associated with early allograft dysfunction in liver transplantation: A prospective observational study.

Perioperative dysfunction of the fibrinolytic system may play a role in adverse outcomes for liver transplant recipients. There is a paucity of data describing the potential impact of the postoperative fibrinolytic system on these outcomes. Our objective was to determine whether fibrinolysis resistance (FR), on postoperative day one (POD-1), was associated with early allograft dysfunction (EAD). We hypothesized that FR, quantified by tissue plasminogen activator thrombelastography, is associated with EAD. Tissue plasminogen activator thrombelastography was performed on POD-1 for 184 liver transplant recipients at a single institution. A tissue plasminogen activator thrombelastography clot lysis at 30 minutes of 0.0% was identified as the cutoff for FR on POD-1. EAD occurred in 32% of the total population. Fifty-nine percent (n=108) of patients were categorized with FR. The rate of EAD was 42% versus 17%, p <0.001 in patients with FR compared with those without, respectively. The association between FR and EAD risk was assessed using multivariable logistic regression after controlling for known risk factors. The odds of having EAD were 2.43 times (95% CI, 1.07-5.50, p =0.03) higher in recipients with FR [model C statistic: 0.76 (95% CI, 0.64-0.83, p <0.001]. An additive effect of receiving a donation after circulatory determination of death graft and having FR in the rate of EAD was observed. Finally, compared with those without FR, recipients with FR had significantly shorter graft survival time ( p =0.03). In conclusion, FR on POD-1 is associated with EAD and decreased graft survival time. Postoperative viscoelastic testing may provide clinical utility in identifying patients at risk for developing EAD, especially for recipients receiving donation after circulatory determination of death grafts.

Preoperative thrombelastography maximum amplitude predicts massive transfusion in liver transplantation.

BACKGROUND: Massive transfusion (MT) is frequently required during liver transplantation. Risk stratification of transplant patients at risk for MT is an appealing concept but remains poorly developed. Thrombelastography (TEG) has recently been shown to reduce mortality when used for trauma resuscitation. We hypothesize that preoperative TEG can be used to risk stratify patients for MT. MATERIAL AND METHODS: Liver transplant patients had blood drawn before surgical incision and assayed via TEG. Preoperative TEG measurements were collected in addition to standard laboratory coagulation tests. TEG variables including R-time (reaction time), angle, maximum amplitude (MA), and LY30 (clot lysis 30 min after MA) were correlated to red blood cell units, plasma (fresh frozen plasma), cryoprecipitate, and platelets during the first 24 h after surgery and tested for their performance using a receiver-operating characteristic curve. RESULTS: Twenty-eight patients were included in the analysis with a median Model for End-Stage Liver Disease score of 17; 36% received a MT. The TEG variables associated with MT (defined as ≥10 red blood cell units/24 h) were a low MA (P < 0.001) and low angle (P = 0.014). A high international normalized ratio of prothrombin time (P = 0.003) and low platelet count (P = 0.007) were also associated with MT. MA had the highest area under the curve (0.861) followed by international normalized ratio of prothrombin time (0.803). An MA of less than 47 mm has a sensitivity of 90% and specificity of 72% to predict a MT. MA was the only coagulation variable that correlated strongly to all blood products transfused. CONCLUSIONS: TEG MA has a high predictability of MT during liver transplantation. The use of TEG preoperatively may help guide more cost effective blood bank preparation for this procedure as only a third of patients required a MT.

Oxalate upregulates expression of IL-2Rß and activates IL-2R signaling in HK-2 cells, a line of human renal epithelial cells.

The role of inflammation in oxalate-induced nephrolithiasis is debated. Our gene expression study indicated an increase in interleukin-2 receptor ß (IL-2Rß) mRNA in response to oxalate (Koul S, Khandrika L, Meacham RB, Koul HK. PLoS ONE 7: e43886, 2012). Herein, we evaluated IL-2Rß expression and its downstream signaling pathway in HK-2 cells in an effort to understand the mechanisms of oxalate nephrotoxicity. HK-2 cells were exposed to oxalate for various time points in the presence or absence of SB203580, a specific p38 MAPK inhibitor. Gene expression data were analyzed by Ingenuity Pathway Analysis software. mRNA expression was quantitated via real-time PCR, and changes in protein expression/kinase activation were analyzed by Western blotting. Exposure of HK-2 cells to oxalate resulted in increased transcription of IL-2Rß mRNA and increased protein levels. Oxalate treatment also activated the IL-2Rß signaling pathway (JAK1/STAT5 phosphorylation). Moreover, the increase in IL-2Rß protein was dependent upon p38 MAPK activity. These results suggest that oxalate-induced activation of the IL-2Rß pathway may lead to a plethora of cellular changes, the most common of which is the induction of inflammation. These results suggest a central role for the p38 MAPK pathway in mediating the effects of oxalate in renal cells, and additional studies may provide the key to unlocking novel biochemical targets in stone disease.

The computerized rounding report: implementation of a model system to support transitions of care.

OBJECTIVES: In response to ACGME work-hour restrictions, residency programs that require continuous inpatient clinical care for educational objectives will be forced to increase the proportion of junior resident experience involved in shift work. Maintaining the balance of education over service at these levels will be a challenge, where a considerable amount of time must be spent gathering data for morning rounds and signing out patients at shift change. Patient safety is an issue with this new paradigm. We hypothesized that computerized sign-out would improve resident efficiency. MATERIALS AND METHODS: A multidisciplinary clinical team collaborated to design a computerized rounding and sign-out (CSO) program to automate collection of clinical information in addition to a brief narrative describing ongoing care issues. Residents returned a self-administered questionnaire before (n = 168) and after implementation (n = 83) examining: pre-rounding time, missed patients, handoff quality, and duty hours. RESULTS: Residents reported spending 11 fewer min/d pre-rounding (P = 0.006). After implementation, residents missed fewer patients on rounds (P = 0.01). A majority (70%) of responders stated that the new program helped them with duty hours. CONCLUSION: The current study demonstrates the reproducibility of the University of Washington model system for rounding and sign-out at an independent site, using basic infrastructure and leadership common to all residency programs. Developing a CSO was associated with a modest reduction in pre-rounding time and fewer patients missed on rounds. Although automating resident tasks may improve workflow in an increasingly complex hospital environment, structured handoff education and other institutional changes are necessary.