Background Little is known about why surrogate decision makers for patients with advanced illness often have overly optimistic expectations about prognosis. Objective To determine how surrogates interpret prognostic statements and to explore factors influencing surrogates’ interpretations of grim prognostic information. Design Multicenter, mixed-methods study. Setting Intensive care units of 3 hospitals in San Francisco, California. Participants 80 surrogates of critically ill patients. Measurements Participants recorded their interpretation of 16 prognostic statements using a standard probability scale. Generalized estimating equations were used to determine whether participants interpreted statements more optimistically as the expressed probability of survival decreased. Fifteen surrogates whose responses exhibited this trend participated in a semistructured interview. Results Participants’ interpretations of prognostic statements expressing a low risk for death were relatively accurate, but interpretations of statements conveying a high risk for death were more optimistic than the actual meaning (P < 0.001; generalized estimating equation model). Interpretations of the statement “90% chance of surviving” did not differ from the actual meaning, but interpretations of “5% chance of surviving” were more optimistic and showed substantial variability (median, 90% [interquartile range, 90% to 95%; P = 0.11] vs. 15% [interquartile range, 5% to 40%; P < 0.001], respectively). Two main themes from the interviews explained this trend: surrogates’ need to register optimism in the face of a poor prognosis and surrogates’ belief that patient attributes unknown to the physician would lead to better-than-predicted outcomes. Limitation Surrogates’ interpretations were elicited in an experimental setting rather than during actual clinician–surrogate conversations. Conclusion Inaccurate interpretations of physicians’ prognostications by surrogates arise partly from optimistic biases rather than simply from misunderstandings. Primary Funding Source National Heart, Lung, and Blood Institute.

We developed a computerized algorithm that accurately detects three types of ventilator dyssynchrony. Double-triggered and flow-limited breaths are associated with the frequent delivery of tidal volumes of greater than 10 mL/kg. Although ventilator dyssynchrony is reduced by deep sedation, potentially deleterious tidal volumes may still be delivered. However, neuromuscular blockade effectively eliminates ventilator dyssynchrony.

Innate immunity is required for effective control of poxvirus infections, but cellular receptors that initiate the host response to these DNA viruses remain poorly defined. Given this information and the fact that functions of TLRs in immunity to DNA viruses remain controversial, we investigated effects of TLR3 on pathogenesis of vaccinia virus, a prototype poxvirus. We used a recombinant strain Western Reserve vaccinia virus that expresses firefly luciferase to infect wild-type C57BL/6 and TLR3−/− mice through intranasal inoculation. Bioluminescence imaging showed that TLR3−/− mice had substantially lower viral replication in the respiratory tract and diminished dissemination of virus to abdominal organs. Mice lacking TLR3 had reduced disease morbidity, as measured by decreased weight loss and hypothermia after infection. Importantly, TLR3−/− mice also had improved survival relative to wild-type mice. Infected TLR3−/− mice had significantly reduced lung inflammation and recruitment of leukocytes to the lung. Mice lacking TLR3 also had lower levels of inflammatory cytokines, including IL-6, MCP-1, and TNF-α in serum and/or bronchoalveolar lavage fluid, but levels of IFN-β did not differ between genotypes of mice. To our knowledge, our findings show for the first time that interactions between TLR3 and vaccinia increase viral replication and contribute to detrimental effects of the host immune response to poxviruses.

Background Lung disease (LD) is the leading cause of death in systemic sclerosis (SSc). The diagnosis of SSc-related LD (SSc-LD) is often a contraindication to lung transplantation (LT) due to concerns that extra-pulmonary involvement will yield worse outcomes. We sought to evaluate post-transplant outcomes in persons with SSc-LD with esophageal involvement compared to persons with non-connective tissue disease related interstitial lung disease (nCTD-ILD). Methods From 1998-2012, persons undergoing LT for SSc-LD were age and gender matched in a 2:1 fashion to controls undergoing LT for nCTD-ILD. Esophageal function was assessed by pH testing and manometry. We defined esophageal dysfunction as the presence of a DeMeester score >14 or dysmotility more severe than “mild non-specific disorder”. The primary outcome was post-transplant survival. Secondary outcomes included freedom from bronchiolitis obliterans syndrome (fBOS) and rates of acute rejection. Survival and fBOS were estimated with Kaplan-Meier methods. Acute rejection was compared with Students t-test. Results Survival was similar in 23 persons with SSc-LD and 46 controls who underwent LT (p=0.47). For the SSc-LD group, 1- and 5-year survival was 83% and 76% compared to 91% and 64% in the nCTD-ILD group. There were no differences in fBOS (p=0.83). Rates of acute rejection were less in SSc-ILD (p=0.05). Esophageal dysfunction was not associated with worse outcomes (p>0.55). Conclusions Persons with SSc-LD appear to have similar survival and fBOS as persons transplanted for nCTD-ILD. The risk of acute rejection after transplant may be reduced in persons with SSc-LD. Esophageal involvement does not appear to impact outcomes.

Unilateral peroneal and sural NCS can accurately screen for CIPNM in ICU patients and detect a limited number of patients that would need concentric needle electromyography to confirm a diagnosis of CIPNM. These results identify a more streamlined method to diagnose CIPNM that may facilitate routine diagnostic testing and monitoring of weakness in critically ill patients.