Background: Cell transplantation is safe in animal models and enhances recovery from stroke in rats. Methods: We studied the safety and feasibility of fetal porcine transplantation in 5 patients with basal ganglia infarcts and stable neurological deficits. To prevent rejection, cells were pretreated with an anti-MHC1 antibody and no immunosuppressive drugs were given to the patients. Results: The first 3 patients had no adverse cell, procedure, or imaging-defined effects. The fourth patient had temporary worsening of motor deficits 3 weeks after transplantation, and the fifth patient developed seizures 1 week after transplantation. MRI in both patients demonstrated areas of enhancement remote from the transplant site, which resolved on subsequent imaging. Two patients showed improvement in speech, language, and/or motor impairments over several months and persisted at 4 years. The study was terminated by the FDA after the inclusion of 5 patients. Conclusion: This is the first report on the transplantation of nontumor cells in ischemic stroke patients.

IMPORTANCE Brain death is the irreversible cessation of function of the entire brain, and it is a medically and legally accepted mechanism of death in the United States and worldwide. Significant variability may exist in individual institutional policies regarding the determination of brain death. It is imperative that brain death be diagnosed accurately in every patient. The American Academy of Neurology (AAN) issued new guidelines in 2010 on the determination of brain death. OBJECTIVE To evaluate if institutions have adopted the new AAN guidelines on the determination of brain death, leading to policy changes. DESIGN, SETTING, AND PARTICIPANTS Fifty-two organ procurement organizations provided US hospital policies pertaining to the criteria for determining brain death. Organizations were instructed to procure protocols specific to brain death (ie, not cardiac death or organ donation procedures). Data analysis was conducted from June 26, 2012, to July 1, 2015.MAIN OUTCOMES AND MEASURES Policies were evaluated for summary statistics across the following 5 categories of data: who is qualified to perform the determination of brain death, what are the necessary prerequisites for testing, details of the clinical examination, details of apnea testing, and details of ancillary testing. We compared these data with the standards in the 2010 AAN update on practice parameters for brain death. RESULTS A total of 508 unique hospital policies were obtained, representing the majority of hospitals in the United States that would be eligible and equipped to evaluate brain death in a patient. Of these, 492 provided adequate data for analysis. Although improvement with AAN practice parameters was readily apparent, there remained significant variability across all 5 categories of data, such as excluding the absence of hypotension (276 of 491 policies [56.2%]) and hypothermia (181 of 228 policies [79.4%]), specifying all aspects of the clinical examination and apnea testing, and specifying appropriate ancillary tests and how they were to be performed. Of the 492 policies, 163 (33.1%) required specific expertise in neurology or neurosurgery for the health care professional who determines brain death, and 212 (43.1%) stipulated that an attending physician determine brain death; 150 policies did not mention who could perform such determination.CONCLUSIONS AND RELEVANCE Hospital policies in the United States for the determination of brain death are still widely variable and not fully congruent with contemporary practice parameters. Hospitals should be encouraged to implement the 2010 AAN guidelines to ensure 100% accurate and appropriate determination of brain death.

Background Little information is available about the geo-economic variations in demographics, management, and outcomes of patients with acute respiratory distress syndrome (ARDS). We aimed to characterise the effect of these geo-economic variations in patients enrolled in the Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE). Methods LUNG SAFE was done during 4 consecutive weeks in winter, 2014, in a convenience sample of 459 intensivecare units in 50 countries across six continents. Inclusion criteria were admission to a participating intensive-care unit (including transfers) within the enrolment window and receipt of invasive or non-invasive ventilation. One of the trial's secondary aims was to characterise variations in the demographics, management, and outcome of patients with ARDS. We used the 2016 World Bank countries classification to define three major geo-economic groupings, namely European high-income countries (Europe-High), high-income countries in the rest of the world (rWORLD-High), and middle-income countries (Middle). We compared patient outcomes across these three groupings. LUNG SAFE is registered with ClinicalTrials.gov, number NCT02010073. Findings Of the 2813 patients enrolled in LUNG SAFE who fulfilled ARDS criteria on day 1 or 2, 1521 (54%) were recruited from Europe-High, 746 (27%) from rWORLD-High, and 546 (19%) from Middle countries. We noted significant geographical variations in demographics, risk factors for ARDS, and comorbid diseases. The proportion of patients with severe ARDS or with ratios of the partial pressure of arterial oxygen (PaO 2) to the fractional concentration of oxygen in inspired air (F I O 2) less than 150 was significantly lower in rWORLD-High countries than in the two other regions. Use of prone positioning and neuromuscular blockade was significantly more common in Europe-High countries than in the other two regions. Adjusted duration of invasive mechanical ventilation and length of stay in the intensive-care unit were significantly shorter in patients in rWORLD-High countries than in Europe-High or Middle countries. High gross national income per person was associated with increased survival in ARDS; hospital survival was significantly lower in Middle countries than in Europe-High or rWORLD-High countries. Interpretation Important geo-economic differences exist in the severity, clinician recognition, and management of ARDS, and in patients' outcomes. Income per person and outcomes in ARDS are independently associated.

A decision to withdraw life-sustaining treatment (WLST) is derived by a conclusion that further treatment will not enable a patient to survive or will not produce a functional outcome with acceptable quality of life that the patient and the treating team regard as beneficial. Although many hospitalized patients die under such circumstances, controlled donation after the circulatory determination of death (cDCDD) programs have been developed only in a reduced number of countries. This International Collaborative Statement aims at expanding cDCDD in the world to help countries progress towards self-sufficiency in transplantation and offer more patients the opportunity of organ donation. The Statement addresses three fundamental aspects of the cDCDD pathway. First, it describes the process of determining a prognosis that justifies the WLST, a decision that should be prior to and independent of any consideration of organ donation and in which transplant professionals must not participate. Second, the Statement establishes the permanent cessation of circulation to the brain as the standard to determine death by circulatory criteria. Death may be declared after an elapsed observation period of 5 min without circulation to the brain, which confirms that the absence of circulation to the brain is permanent. Finally, the Statement highlights the value of perfusion repair for increasing the success of cDCDD organ transplantation. cDCDD protocols may utilize either in situ or ex situ perfusion consistent with the practice of each country. Methods to accomplish the in situ normothermic reperfusion of organs must preclude the restoration of brain perfusion to not invalidate the determination of death.