Eligibility for organ donation: a medico-legal perspective on defining and determining death

Purpose: In the context of post-mortem organ donation, there is an obvious need for certainty regarding the legal definition and determination of death, as individuals must be legally pronounced dead before organs may be procured for donation. Surprisingly then, the legal situation in Canada with regard to the definition and determination of death is uncertain. The purpose of this review is to provide anesthesiologists and critical care specialists with a medico-legal perspective regarding the definition and determination of death (particularly as it relates to non-heart-beating donor protocols) and to contribute to ongoing improvement in policies, protocols, and practices in this area. Principal findings: The status quo with regard to the current legal definition of death is presented as well as the criteria for determining if and when death has occurred. A number of important problems with the status quo are described, followed by a series of recommendations to address these problems. Conclusions: The legal deficiencies regarding the definition and determination of death in Canada may place health care providers at risk of civil or criminal liability, discourage potential organ donation, and frustrate the wishes of some individuals to donate their organs. The definition and criteria for the determination of death should be clearly set out in legislation. In addition, the current use of non-heart-beating donor protocols in Canada will remain inconsistent with Canadian law until more persuasive evidence on the potential return of cardiac function after cardiac arrest is gathered and made publicly available or until a concrete proposal to abandon the dead donor rule and amend Canadian law is adopted following a process of public debate and intense multidisciplinary review

Recovery of neurofilament following early monocular deprivation

Postnatal development of the mammalian geniculostriate visual pathway is partly guided by visually driven activity. Disruption of normal visual input during certain critical periods can alter the structure of neurons, as well as their connections and functional properties. Within the layers of the dorsal lateral geniculate nucleus (dLGN), a brief early period of monocular deprivation can alter the structure and soma size of neurons within deprived-eye-receiving layers. This modification of structure is accompanied by a marked reduction in labeling for neurofilament protein, a principle component of the stable cytoskeleton. This study examined the extent of neurofilament recovery in monocularly deprived cats that either had their deprived eye opened (binocular recovery), or had the deprivation reversed to the fellow eye (reverse occlusion). The loss of neurofilament and the reduction of soma size caused by monocular deprivation were ameliorated equally and substantially in both recovery conditions after 8 days. The degree to which this recovery was dependent on visually driven activity was examined by placing monocularly deprived animals in complete darkness. Though monocularly deprived animals placed in darkness showed recovery of soma size in deprived layers, the manipulation catalyzed a loss of neurofilament labeling that extended to non-deprived layers as well. Overall, these results indicate that both recovery of soma size and neurofilament labeling is achieved by removal of the competitive disadvantage of the deprived eye. However, while the former occurred even in the absence of visually driven activity, recovery of neurofilament did not. The finding that a period of darkness produced an overall loss of neurofilament throughout the dLGN suggests that this experiential manipulation may cause the visual pathways to revert to an earlier more plastic developmental stage. It is possible that short periods of darkness could be incorporated as a component of therapeutic measures for treatment of deprivation-induced disorders such as amblyopia

No Evidence for a Cumulative Impact Effect on Concussion Injury Threshold

Recent studies using a helmet-based accelerometer system (Head Impact Telemetry System [HITS]) have demonstrated that concussions result from a wide range of head impact magnitudes. Variability in concussion thresholds has been proposed to result from the cumulative effect of non-concussive head impacts prior to injury. We used the HITS to collect biomechanical data representing >100,000 head impacts in 95 high school football players over 4 years. The cumulative impact histories prior to 20 concussive impacts in 19 athletes were compared to the cumulative impact histories prior to the three largest magnitude non-concussive head impacts in the same athletes. No differences were present in any impact history variable between the concussive and non-concussive high magnitude impacts. These analyses included the number of head impacts, cumulative HIT severity profile value, cumulative linear acceleration, and cumulative rotational acceleration during the same practice or game session, as well as over the 30-min and 1 week preceding these impacts. Our data do not support the proposal that impact volume or intensity influence concussion threshold in high school football athletes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90490/1/neu-2E2011-2E1910.pd

3-Year Comparison of Drug-Eluting Versus Bare-Metal Stents

ObjectivesThe aim of this study was to compare 3-year cumulative outcomes to landmark second- and third-year outcomes with the routine use of drug-eluting stents (DES) (>75% “off-label”) with a comparable group treated with bare-metal stents (BMS).BackgroundLong-term safety concerns after “off-label” DES use persist, despite recent 2-year data showing comparable safety to BMS use.MethodsClinical outcomes (nonfatal myocardial infarction, all-cause mortality) were assessed in 1,147 consecutive patients who received a BMS in the year before the introduction of DES at Wake Forest University Baptist Medical Center and 1,246 consecutive patients that received a DES after it became our routine choice with equivalent complete 3-year follow-up.ResultsStents were used for “off-label” indications in 80% of DES patients. At 3 years, the hazard ratio for DES compared with BMS for cumulative target vessel revascularization was 0.65 (95% confidence interval [CI]: 0.51 to 0.82), nonfatal myocardial infarction or death was 0.85 (95% CI: 0.71 to 1.03), and all-cause mortality 0.80 (95% CI: 0.64 to 1.01). The DES clinical benefits occurred entirely within the first year, with similar rates of these clinical end points in the second and third year. The cumulative hazard ratio of stent thrombosis DES compared with BMS was 1.07 (95% CI: 0.57 to 2.01), with similar rates of stent thrombosis in the third year (p = 0.70).ConclusionsThe routine clinical use of DES for “off-label” indications was associated with lower clinical end points at 3 years than treatment with BMS in a comparable group of patients, with similar cumulative rates of stent thrombosis. There was no evidence of late “catch-up” of adverse DES events

Shotgun metagenomic analysis of microbial communities from the Loxahatchee nature preserve in the Florida Everglades.

BackgroundCurrently, much is unknown about the taxonomic diversity and the mechanisms of methane metabolism in the Florida Everglades ecosystem. The Loxahatchee National Wildlife Refuge is a section of the Florida Everglades that is almost entirely unstudied in regard to taxonomic profiling. This short report analyzes the metagenome of soil samples from this Refuge to investigate the predominant taxa, as well as the abundance of genes involved in environmentally significant metabolic pathways related to methane production (nitrogen fixation and dissimilatory sulfite reduction).MethodsShotgun metagenomic sequencing using the Illumina platform was performed on 17 soil samples from four different sites within the Loxahatchee National Wildlife Refuge, and underwent quality control, assembly, and annotation. The soil from each sample was tested for water content and concentrations of organic carbon and nitrogen.ResultsThe three most common phyla of bacteria for every site were Actinobacteria, Acidobacteria, and Proteobacteria; however, there was variation in relative phylum composition. The most common phylum of Archaea was Euryarchaeota for all sites. Alpha and beta diversity analyses indicated significant congruity in taxonomic diversity in most samples from Sites 1, 3, and 4 and negligible congruity between Site 2 and the other sites. Shotgun metagenomic sequencing revealed the presence of biogeochemical biomarkers of particular interest (e.g., mrcA, nifH, and dsrB) within the samples. The normalized abundances of mcrA, nifH, and dsrB exhibited a positive correlation with nitrogen concentration and water content, and a negative correlation with organic carbon concentration.ConclusionThis Everglades soil metagenomic study allowed examination of wetlands biological processes and showed expected correlations between measured organic constituents and prokaryotic gene frequency. Additionally, the taxonomic profile generated gives a basis for the diversity of prokaryotic microbial life throughout the Everglades

Outcomes in patients with gunshot wounds to the brain.

Introduction:Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. Methods:We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. Results:825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. Conclusion:We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. Level of evidence:Level II

The accuracy of the report of hepatic steatosis on ultrasonography in patients infected with hepatitis C in a clinical setting: A retrospective observational study

BACKGROUND: Steatosis is occasionally reported during screening ultrasonography in patients with hepatitis C virus (HCV). We conducted a retrospective observational study to assess the factors associated with steatosis on ultrasonography and the relationship between steatosis on ultrasound versus biopsy in patients infected with HCV in a clinical setting. Our hypothesis was ultrasonography would perform poorly for the detection of steatosis outside of the context of a controlled study, primarily due to false-positive results caused by hepatic fibrosis and inflammation. METHODS: A retrospective review of ultrasound reports was conducted on patients infected with HCV in a tertiary care gastroenterology clinic. Reports were reviewed for the specific documentation of the presence of steatosis. Baseline clinical and histologic parameters were recorded, and compared for patients with vs. without steatosis. Multiple logistic regression analysis was performed on these baseline variables. Liver biopsies were reviewed by two pathologists, and graded for steatosis. Steatosis on biopsy was compared to steatosis on ultrasound report, and the performance characteristics of ultrasonography were calculated, using biopsy as the gold standard. RESULTS: Ultrasound reports were available on 164 patients. Patients with steatosis on ultrasound had a higher incidence of the following parameters compared to patients without steatosis: diabetes (12/49 [24%] vs. 7/115 [6%], p < 0.001), fibrosis stage >2 (15/48 [31%] vs. 16/110 [15%], p = 0.02), histologic grade >2 (19/48 [40%] vs. 17/103 [17%], p = 0.002), and ALT (129.5 ± 89.0 IU/L vs. 94.3 ± 87.0 IU/L, p = 0.01). Histologic grade was the only factor independently associated with steatosis with multivariate analysis. When compared to the histologic diagnosis of steatosis (n = 122), ultrasonography had a substantial number of false-positive and false-negative results. In patients with a normal ultrasound, 8/82 (10%) had >30% steatosis on biopsy. Among patients with steatosis reported on ultrasound, only 12/40 (30%) had >30% steatosis on biopsy review. CONCLUSION: Steatosis on ultrasound is associated with markers of inflammation and fibrosis in HCV-infected patients, but does not consistently correlate with steatosis on biopsy outside of the context of a controlled study. Clinicians should be skeptical of the definitive diagnosis of steatosis on hepatic ultrasonography