A ubiquitin-like protein unleashes ubiquitin ligases.

Modification of cullin-RING ubiquitin ligases by the ubiquitin-like molecule Nedd8 promotes substrate ubiquitination. A crystal structure of a cullin modified by Nedd8 recently reported in Cell (Duda et al., 2008) and a biochemical study in Molecular Cell (Saha and Deshaies, 2008) reveal the dramatic impact on the ligase machinery by conjugation of ubiquitin or ubiquitin-like proteins.

Transfusion-associated hyperkalemia in pediatric population: Prevalence, risk factors, survival, infusion rate, and RBC unit features.

BACKGROUND: Hyperkalemia is a rare life-threatening complication of red blood cell (RBC) transfusion. Stored RBCs leak intracellular potassium (K+) into the supernatant; irradiation potentiates the K+ leak. As the characteristics of patients and implicated RBCs have not been studied systematically, a multicenter study of transfusion-associated hyperkalemia (TAH) in the pediatric population was conducted through the AABB Pediatric Transfusion Medicine Subsection. STUDY DESIGN: The medical records of patients <18 years old were retrospectively queried for hyperkalemia occurrence during or ≤12 h after the completion of RBC transfusion in a 1-year period. Collected data included patient demographics, diagnosis, medical history, timing of hyperkalemia and transfusion, mortality, and RBC unit characteristics. RESULTS/FINDINGS: A total of 3777 patients received 19,649 RBC units during the study period in four facilities. TAH was found in 35 patients (0.93%) in 37 occurrences. The patient median age and weight were 1.28 years and 9.80 kg, respectively. All patients had multiple serious comorbidities. There were 79 RBC units transfused in the TAH events; 62% were irradiated, and the median age of the units was 10 days. The median total RBC volume transfused ≤12 h before TAH was 24% of patient estimated total blood volume, and the median infusion rate (IR) was19.6 ml/kg/h. Mortality rate within 1 day after the TAH event was 20%. CONCLUSIONS: The prevalence of TAH in children was low; however, the 1-day mortality rate was 20%. Patients with multiple comorbidities may be at higher risk for TAH. The IR was higher for patients who had TAH than the IR threshold for safe transfusion.

Emergency departments are higher-risk locations for wrong blood in tube errors.

BACKGROUND: Wrong blood in tube (WBIT) errors can lead to ABO mistransfusions. It is unknown if WBIT errors are more likely in specific healthcare locations or if specific collection practices influence the commission of WBIT errors. STUDY DESIGN AND METHODS: Data on pretransfusion samples from calendar year 2019 were collected retrospectively by 39 transfusion services in nine countries. We compared the proportion of WBIT errors made in emergency departments (EDs), inpatient wards, and outpatient clinics. RESULTS: In total, 143 WBIT errors were detected among 1,394,862 samples for an unadjusted aggregate WBIT proportion of 1.03/10,000 samples. Using a pooled random effects model, the WBIT proportion was estimated to be significantly higher in EDs (1.23/10,000 samples, 95% CI 0.62-2.43) than inpatient wards (0.71/10,000, 95% CI 0.44-1.14; p < .001) or outpatient clinics (0.24/10,000, 95% CI 0.08-0.65; p < .001) and significantly higher in inpatient wards than outpatient clinics (p = .043). The use of electronic positive patient identification (ePPID) systems was associated with a significantly lower WBIT proportion in the ED (odds ratio, OR: 0.32, 95% CI: 0.11-0.96, p = .041), but not in inpatient wards (OR: 0.45, 95% CI: 0.20-1.01, p = .054) or outpatient clinics (OR: 1.95, 95% CI: 0.39-9.74, p = .415). DISCUSSION: Normalized for the number of samples drawn per location, the WBIT proportion in EDs was 1.7 times higher than inpatient wards and 5.1 times higher than outpatient clinics. EDs represent higher-risk clinical locations for WBIT errors, and electronic positive patient identification (ePPID) may provide a greater impact on safety in EDs relative to other clinical areas.

Outcomes in necrotizing soft tissue infections treated with therapeutic plasma exchange.

BACKGROUND: Treatment of necrotizing soft tissue infections (NSTIs) includes prompt surgical debridement and antibiotics, but despite standard care, the morbidity and mortality remain high. Since therapeutic plasma exchange (TPE) has been considered for treatment of severe sepsis, this study evaluates the efficacy of TPE for patients with NSTI. STUDY DESIGN AND METHODS: This is a retrospective study of patients with diagnosis of NSTI who received treatment with and without TPE over an 11-year period. The primary outcome was in-hospital mortality. RESULTS: Fifty-two patients with NSTI treated with TPE (TPE group) and 125 patients with NSTI not treated with TPE (non-TPE group) were assessed. Nineteen (36.5%) patients died in the TPE group, and 35 (28%) patients died in the non-TPE group. Within the TPE group, there was significant improvement in white blood cell (WBC) count and sodium levels 7 days after TPE treatment, but no improvement in creatinine. Inverse probability weighting based on propensity scores was used to compare survival in the TPE and non-TPE groups and demonstrated that TPE was associated with an increased odds of death (odds ratio, 2.8). A second analysis matched for six variables yielded 31 pairs and demonstrated no significant difference in mortality or length of stay. CONCLUSIONS: This study describes the largest series of patients with NSTIs treated with TPE and showed no evidence of clinical benefit. Further carefully designed studies with meaningful clinical endpoints would prove useful in assessing reproducibility and determining if there is a role for TPE in other forms of severe sepsis.

Apheresis for babesiosis: Therapeutic parasite reduction or removal of harmful toxins or both?

Babesiosis is a potentially life-threatening illness caused by intraerythrocytic protozoan parasites of the genus Babesia that are transmitted most commonly by Ixodes ticks, and rarely from blood transfusion or congenitally. Clinical presentations of babesiosis include asymptomatic infection, mild to moderate disease, or severe disease. Antibiotics such as atovaquone plus azithromycin or clindamycin and quinine can be used effectively to treat this disease in most cases, however in high risk populations, the mortality rate can be as high as 20% despite therapy. Therapeutic exchange transfusion has been used in severe babesiosis and is of apparent therapeutic benefit. It is not entirely clear through what mechanism therapeutic exchange transfusion may help patients. Data suggests that in addition to parasite load reduction, it is possible that therapeutic exchange transfusion removes toxins generated by babesia infection. There are many remaining questions that need to be addressed regarding exchange transfusion for babesiosis. J. Clin. Apheresis 31:454-458, 2016. © 2015 Wiley Periodicals, Inc.

Factors influencing naproxen metabolite interference in total bilirubin assays.

BACKGROUND: The factors influencing naproxen metabolite O-desmethylnaproxen (ODMN) positive interference in diazo-based Jendrassik and Grof (JG) total bilirubin (Tbil) assays and lack of interference in direct bilirubin (Dbil) assays have not been resolved. The objective of this study was to understand the conditions causing this interference pattern. METHODS: Pooled normal and ultra-filtered plasma samples spiked with ODMN and naproxen were measured on the Beckman Coulter DxC and AU instruments. Absorbance spectra were obtained for ODMN mixed with Dbil reagent at original and adjusted pH. Absorbance spectra were also obtained for ODMN and bilirubin samples mixed with Tbil assay reagents. RESULTS: ODMN produces a positive interference in the DxC JG Tbil assays, but not the AU Tbil or Dbil assays or the DxC Dbil assay. Neutralizing the acidic pH of AU and DxC Dbil reagents allows ODMN to react with diazo salts. ODMN samples mixed with DxC and AU Tbil reagents produce broad peaks from 450 to 560nm and 400 to 540nm, respectively. The DxC JG Tbil assay monitors a change in absorbance at 520nm close to peak absorbance wavelength of diazo-reacted ODMN, whereas the AU Tbil assay monitors a change in absorbance at 570/660nm, beyond the peak absorbance wavelengths of diazo-reacted ODMN. CONCLUSION: The acidic pH of diazo-based Dbil assay reagents inhibits the reaction of ODMN with diazo salts. The AU JG Tbil assay is a reliable method to measure Tbil in the setting of naproxen overdose.