A systematic review of transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of blood transfusion. The clinicolaboratory features of TA-GVHD and the relative contributions of recipient and component factors remain poorly understood. We conducted a systematic review of TA-GVHD reports. The HLA relationship between donor and recipient was classified as D = 0 when no donor antigens were foreign to the recipient vs D ≥ 1 when ≥1 donor antigen disparity occurred. We identified 348 unique cases. Criteria for component irradiation were met in 48.9% of cases (34.5% immune-compromised, 14.4% related-donor), although nonirradiated components were transfused in the vast majority of these (97.6%). Components were typically whole blood and red cells. When reported, component storage duration was ≤10 days in 94%, and 23 (6.6%) were leukoreduced (10 bedside, 2 prestorage, and 11 unknown). Among 84 cases with HLA data available, the category of D = 0 was present in 60 patients (71%) at either HLA class I or II loci and was more common among recipients without traditional indications for component irradiation. These data challenge the historic emphasis on host immune defects in the pathogenesis of TA-GVHD. The dominant mechanism of TA-GVHD in both immunocompetent and compromised hosts is exposure to viable donor lymphocytes not recognized as foreign by, but able to respond against, the recipient.

Management and outcomes of cancer-associated venous thromboembolism in patients with concomitant thrombocytopenia: a retrospective cohort study.

Venous thromboembolism (VTE) and thrombocytopenia are both more common in cancer patients than in general populations. Both the outcomes and optimal management of cancer-associated VTE in thrombocytopenic patients are unknown. The objective of the current  study is to describe a cohort of patients presenting with acute cancer-associated VTE with concomitant thrombocytopenia, including management patterns and outcomes. We conducted a retrospective cohort study of all cancer patients admitted to a regional cancer centre and the main university hospital's hematology service in Edmonton, Alberta, from 2005-2011, who had thrombocytopenia at the time of acute VTE. We report rates of recurrent symptomatic thromboembolism, major and clinically relevant non-major bleeding, within the initial 3 months following VTE diagnosis. Seventy-four patients were identified as eligible and reviewed. Seventeen (23.0 %) patients did not receive any antithrombotic therapy, 30 (40.5 %) received a minimum of 3 months of full-dose anticoagulation, and 27 (36.5 %) received partial treatment, which was either dose-reduced, interrupted, or shortened in duration. Twenty-three (31.1 %) experienced recurrent thromboembolism and 13 (17.6 %) had bleeding events, of which 3 (4.1 %) were major. In conclusion, patients with acute cancer-associated VTE and concomitant thrombocytopenia were managed heterogeneously at our institution, without a predominant strategy. There was a high rate of short-term complications, including recurrent thromboembolism and hemorrhage in this cohort. Future research should focus on determining the optimal management strategy in this challenging clinical scenario.

Risk factors and outcomes associated with acute kidney injury following ruptured abdominal aortic aneurysm.

BACKGROUND: Current data describing the epidemiology of acute kidney injury (AKI) following repair of ruptured abdominal aortic aneurysm (rAAA) are limited and long-term outcomes are largely unknown. Our objectives were to describe the incidence rate, risk factors, clinical course and long-term outcomes of AKI following rAAA repair. METHODS: Retrospective population-based cohort study of all referrals undergoing emergency repair of rAAA in Northern Alberta from January 1, 2002 to December 31 2009. Demographic, clinical, physiologic and laboratory data were extracted. AKI was defined and classified according to the AKIN criteria. RESULTS: In total, 140 patients survived to receive emergent rAAA repair. Post-operative AKI occurred in 75.7% of patients (n = 106), 78.3% (n = 83) of which occurred during the initial 24 hours of ICU admission. AKIN stage 1, 2, and 3 occurred in 47 (33.6%), 36 (25.7%) and 23 (16.4%), respectively, with 19 patients receiving renal replacement therapy (RRT). Several clinical and biochemical patient factors were associated with incident AKI, including baseline estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² (odds ratio [OR] 2.94; 95% CI, 1.15-7.51, p = 0.03), need for mechanical ventilation (OR 22.7; 95% CI, 7.0-72.1, p < 0.0001) and vasoactive therapy (OR 9.9; 95% CI, 3.0-32.2, p < 0.0001) and higher mean APACHE II scores (25.7 [8.2] vs. 16.3 [4.9], p < 0.0001). AKI was associated with a higher ICU (28.3% vs. 0%; p = 0.0008) and in-hospital case-fatality rate (35.9% vs. 0%, p = 0.0001). Of 102 survivors to discharge, 65.7% (n = 67) recovered to baseline kidney function. In multivariable analysis, greater severity of AKI (OR 5.01; 95% CI, 2.34-10.7, p < 0.001) and lower baseline eGFR (OR 0.96; 95% CI, 0.93-0.99, p = 0.03) were associated with non-recovery. AKI remained independently associated with 1-year mortality after adjusting for age, sex, comorbidity, and illness severity (OR 5.21; 95% CI, 1.04-26.2, p = 0.045; AUC 0.83; H-L GoF, p = 0.26). Among survivors at 1-year, only 63.4% (n = 55) had complete kidney recovery. CONCLUSIONS: Following rAAA repair, AKI is a common complication independently associated with long-term post-operative mortality. A significant proportion of AKI sufferers in this setting fail to recover to baseline kidney function.

Elevated cardiac troponin in the early post-operative period and mortality following ruptured abdominal aortic aneurysm: a retrospective population-based cohort study.

INTRODUCTION: Cardiac complications are potentially life-threatening following emergency repair of ruptured abdominal aortic aneurysms (rAAA). Our objectives were to describe the incidence, risk factors, cardiac outcomes and mortality associated with elevated cardiac-specific troponin (cTnI) following repair of rAAA. We hypothesized that early post-operative cTnI elevation (>0.15 mcg/L) in rAAA patients would identify a high-risk subgroup for cardiovascular complications and adverse outcomes. METHODS: This was a retrospective population-based cohort study of all referrals for emergency repair of rAAA in central and northern Alberta, from 1 January 2002 to 31 December 2009. Demographic, clinical, physiologic and laboratory data were extracted, along with cardiac-specific investigations and events in the 72 hours following rAAA repair. RESULTS: In total, 55% of patients (n = 77/141) had elevated cTnI, of which 12% (n = 9) had ST segment elevation, 23% (n = 18) had ST segment depression, 5% (n = 4) had other ECG changes, and 61% (n = 47) had no diagnostic ECG changes. Those with positive cTnI were more likely to have coronary artery disease (45.5% vs. 23.4%, P = 0.01) and higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores (24.9 vs. 21.4, n = 0.016). cTnI positive patients were more likely to receive vasoactive support (58.4% vs. 14.1%, P < 0.001), had longer intensive care unit (ICU) lengths of stay (8 (3 to 11) vs. 4 (2 to 9) days, P = 0.02) and higher adjusted in-hospital mortality (40.3% vs. 14.1%; OR 4.23; 95% CI, 1.47 to 12.1; P = 0.007). CONCLUSIONS: Elevated cTnI early after rAAA repair is an independent predictor for post-operative complications and death.

Germline MYH mutations in a clinic-based series of Canadian multiple colorectal adenoma patients.

OBJECTIVES: MYH is a member of the DNA base excision repair (BER) pathway and mutations of this gene predispose to the development of colorectal neoplasia in an autosomal recessive transmission pattern. Our objective was to determine the significance of MYH mutations in a series of Canadian patients with multiple adenomas. METHODS: We screened for germline MYH mutations (by dHPLCO) in 20 clinic-based multiple adenoma patients who were adenomatous polyposis coli (APC) mutation-negative. Suspected mutations were confirmed by sequence analysis. RESULTS: Six of 20 (30%) patients carried pathogenic biallelic MYH mutations, 1 Y165C homozygote and 5 compound heterozygotes of other sequence variants. We identified three novel variants, Q377X, 1314delA, and P281L, which are likely pathogenic. Twenty-nine relatives of the Y90X/1103delC compound heterozygous carrier were also screened for germline MYH mutations, and 1 homozygous and 14 heterozygous carriers were identified. CONCLUSIONS: Among patients with multiple adenomas, biallelic MYH mutations account for approximately 30% of APC mutation negative cases and two thirds of these carry mutations other than the "common" Y165C and G382D variants. Clinical screening algorithms which focus only on the Y165C and G382D alleles are inadequate since additional pathogenic mutations may be identified by screening the entire gene.