Citations

Abstract Rationale Respiratory failure represents a major risk for morbidity and mortality. Although generally managed in the intensive care unit (ICU), respiratory failure often begins elsewhere. Checklists of care processes to minimize the duration of mechanical ventilation and adverse events are routinely used in the ICU, but are uncommonly used outside the ICU. Objectives To develop consensus among a multidisciplinary expert panel on care practices to include in a checklist of best practices for critically ill patients with respiratory failure before and after ICU admission. Methods A multidisciplinary expert panel was assembled. The panel was tasked with creating a checklist of care processes aimed at decreasing progression to respiratory failure, duration of mechanical ventilation, mortality in mechanical ventilation, and adverse events. Over the course of multiple teleconferences and e-mail communications, the Prevention of Organ Failure Checklist list was reviewed, refined, and voted upon. Items that received greater than 75% of the vote were included in the final checklist. Measurements and Main Results: Using a modified Delphi process, the expert panel was able to compile Prevention of Organ Failure Checklist into 20 items that aimed to decrease mechanical ventilation by assessing the causes of acute respiratory failure, ventilation strategies, sedation, and general critical care processes, as well as to avoid unwanted or nonbeneficial interventions. Conclusions The modified Delphi process identified readily available preventative interventions suitable for checklist implementation in patients with or progressing to respiratory failure even before ICU admission.

PurposeQuantification of tissue stiffness may facilitate identification of abnormalities in orofacial muscle tone and thus contribute to differential diagnosis of dysarthria. Tissue stiffness is affected by muscle tone as well as age-related changes in muscle and connective tissue.MethodThe Myoton-3 measured tissue stiffness in 40 healthy adults, including equal numbers of men and women in each of two age groups: 18–40 years and 60+ years. Data were collected from relaxed muscles at the masseter, cheek, and lateral tongue surfaces in two positions: reclined on the side and seated with head tilted.ResultsTissue stiffness differed across age, sex, and measurement site with multiple interaction effects. Overall, older subjects exhibited higher stiffness coefficients and oscillation frequency measures than younger subjects whereas sex differences varied by tissue site. Effects of body position were inconsistent across tissue site and measurement.ConclusionsAlthough older subjects were expected to have lower muscle tone, age-related nonmuscular tissue changes may have contributed to yield a net effect of higher stiffness. These data raise several considerations for the development of accurate normative data and for future diagnostic applications of tissue stiffness assessment.

BACKGROUND Pulmonary transfusion reactions are important complications of blood transfusion, yet differentiating these clinical syndromes is diagnostically challenging. We hypothesized that biologic markers of inflammation could be used in conjunction with clinical predictors to distinguish transfusion‐related acute lung injury (TRALI), transfusion‐associated circulatory overload (TACO), and possible TRALI. STUDY DESIGN AND METHODS In a nested case‐control study performed at the University of California at San Francisco and Mayo Clinic, Rochester, we evaluated clinical data and blood samples drawn before and after transfusion in patients with TRALI (n = 70), possible TRALI (n = 48), TACO (n = 29), and controls (n = 147). Cytokines measured included granulocyte‐macrophage–colony‐stimulating factor, interleukin (IL)‐6, IL‐8, IL‐10, and tumor necrosis factor‐α. Logistic regression and receiver operating characteristics curve analyses were used to determine the accuracy of clinical predictors and laboratory markers in differentiating TACO, TRALI, and possible TRALI. RESULTS Before and after transfusion, IL‐6 and IL‐8 were elevated in patients with TRALI and possible TRALI relative to controls, and IL‐10 was elevated in patients with TACO and possible TRALI relative to that of TRALI and controls. For all pulmonary transfusion reactions, the combination of clinical variables and cytokine measurements displayed optimal diagnostic performance, and the model comparing TACO and TRALI correctly classified 92% of cases relative to expert panel diagnoses. CONCLUSIONS Before transfusion, there is evidence of systemic inflammation in patients who develop TRALI and possible TRALI but not TACO. A predictive model incorporating readily available clinical and cytokine data effectively differentiated transfusion‐related respiratory complications such as TRALI and TACO.

Background Possible transfusion‐related acute lung injury (p TRALI ) cases by definition have a clear temporal relationship to an alternative recipient risk factor for acute respiratory distress syndrome ( ARDS ). We questioned whether transfusion factors are important for the development of p TRALI . Study Design and Methods In this nested case‐control study, we prospectively identified 145 consecutive patients with p TRALI and randomly selected 163 transfused controls over a 4‐year period at the U niversity of C alifornia at S an F rancisco and the M ayo C linic ( R ochester, M innesota). Results For p TRALI , we found evidence against transfusion being important: receipt of plasma from female donors (odds ratio [ OR ], 0.82; 95% confidence interval [ CI ], 0.29‐2.3; p = 0.70), total number of units transfused ( OR , 0.99; 95% CI , 0.89‐1.10; p = 0.86), and number of red blood cell and whole blood units transfused ( OR , 0.78; 95% CI , 0.59‐1.03; p = 0.079). In contrast, we found that risk for p TRALI was associated with additional recipient factors: chronic alcohol abuse ( OR , 12.5; 95% CI , 2.8‐55; p < 0.001), current smoker ( OR , 4.2; 95% CI , 1.67‐10.8; p = 0.0024), shock before transfusion ( OR , 4.6; 95% CI , 2.0‐10.7; p < 0.001), and positive fluid balance before transfusion ( OR , 1.32/ L ; 95% CI , 1.20‐1.44; p < 0.001). Conclusion Recipient risk factors for ARDS rather than transfusion risk factors predominate in p TRALI .

BackgroundIdentifying antibodies to HLA (anti‐HLA) by solid‐phase assays is used to screen blood donors to mitigate transfusion‐related acute lung injury risk. Various cutoffs for detection assays have been proposed in the literature; however, these do not take into consideration lot‐to‐lot variability of commercially available assays.Study Design and MethodsSamples from 93 nontransfused males were tested using five different lots of a multiplex bead‐based anti‐HLA detection kit. A subset of 17 samples was tested on 5 days using a single lot. An additional 96 samples from donations with varied anti‐HLA levels were tested using kits from two different lots. Results were reported as a normalized background (NBG) ratio.ResultsFor the 93 nontransfused donors, NBG values generated using the reference lot were significantly higher than those obtained with three of the four comparator lots. However, for the 96 samples with low‐, moderate‐, and higher‐level anti‐HLA, Class I (CL‐I) values were 1.4 times lower and Class II (CL‐II) values were 1.2 times lower using the reference versus comparator lot. For CL‐I antibodies the between‐lot standard deviation (SD) was 1.36 (95% confidence interval [CI], 1.19‐1.60), while the between‐day SD was 1.27 (95% CI, 1.08‐1.52). Similarly, for CL‐II antibodies the between‐lot SD was 0.81 (95% CI, 0.70‐0.95), while the between‐day SD was 0.50 (95% CI, 0.43‐0.60).ConclusionsThere is interlot variability in the tested HLA detection assay as well as significant bias between lots. It may be reasonable to develop a new cutoff when a new lot is obtained.

AbstractTransfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality. To determine TRALI incidence by prospective, active surveillance and to identify risk factors by a case-control study, 2 academic medical centers enrolled 89 cases and 164 transfused controls. Recipient risk factors identified by multivariate analysis were higher IL-8 levels, liver surgery, chronic alcohol abuse, shock, higher peak airway pressure while being mechanically ventilated, current smoking, and positive fluid balance. Transfusion risk factors were receipt of plasma or whole blood from female donors (odds ratio = 4.5, 95% confidence interval [CI], 1.85-11.2, P = .001), volume of HLA class II antibody with normalized background ratio more than 27.5 (OR = 1.92/100 mL, 95% CI, 1.08-3.4, P = .03), and volume of anti–human neutrophil antigen positive by granulocyte immunofluoresence test (OR = 1.71/100 mL, 95% CI, 1.18-2.5, P = .004). Little or no risk was associated with older red blood cell units, noncognate or weak cognate class II antibody, or class I antibody. Reduced transfusion of plasma from female donors was concurrent with reduced TRALI incidence: 2.57 (95% CI, 1.72-3.86) in 2006 versus 0.81 (95% CI, 0.44-1.49) in 2009 per 10 000 transfused units (P = .002). The identified risk factors provide potential targets for reducing residual TRALI.

In comparing gene expression of normal and CML CD34+ quiescent (G0) cell, 292 genes were downregulated and 192 genes upregulated in the CML/G0 Cells. The differentially expressed genes were grouped according to their reported functions, and correlations were sought with biological differences previously observed between the same groups. The most relevant findings include the following. (i) CML G0 cells are in a more advanced stage of development and more poised to proliferate than normal G0 cells. (ii) When CML G0 cells are stimulated to proliferate, they differentiate and mature more rapidly than normal counterpart. (iii) Whereas normal G0 cells form only granulocyte/monocyte colonies when stimulated by cytokines, CML G0 cells form a combination of the above and erythroid clusters and colonies. (iv) Prominin-1 is the gene most downregulated in CML G0 cells, and this appears to be associated with the spontaneous formation of erythroid colonies by CML progenitors without EPO.

Pulmonary hemangiomas are exceptionally rare in childhood and more so in infancy. They may involve the airways or the parenchyma, and may be localized or multifocal. We present two cases of pulmonary capillary hemangiomas. The first case is a localized form of capillary hemangioma that was resected from an 8-week-old infant with signs of respiratory distress. A computed tomography scan showed a cystic mass initially thought to be an intrapulmonary bronchogenic cyst. A segmental resection was performed and examination revealed a localized capillary hemangioma without cystic or cavernous features. The second case is an example of a multifocal capillary hemangioma from a 9-year-old child who presented clinically with clubbing of fingers and toes and radiologically had multiple discrete nodules localized to the right lung. The clinical and pathological features of the cases are discussed together with a review of the literature. The distinction from other vascular neoplasms of childhood is briefly described. Although rare, pulmonary hemangiomas should be entertained in the diagnosis of both solid and cystic intrapulmonary lesions of childhood and infancy.