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The ethics of testing and research of manufactured organs on brain-dead/recently deceased subjects

Parent, Brendan; Gelb, Bruce; Latham, Stephen; Lewis, Ariane; Kimberly, Laura L; Caplan, Arthur L
Over 115 000 people are waiting for life-saving organ transplants, of whom a small fraction will receive transplants and many others will die while waiting. Existing efforts to expand the number of available organs, including increasing the number of registered donors and procuring organs in uncontrolled environments, are crucial but unlikely to address the shortage in the near future and will not improve donor/recipient compatibility or organ quality. If successful, organ bioengineering can solve the shortage and improve functional outcomes. Studying manufactured organs in animal models has produced valuable data, but is not sufficient to understand viability in humans. Before risking manufactured organ experimentation in living humans, study of bioengineered organs in recently deceased humans would facilitate evaluation of the function of engineered tissues and the complex interactions between the host and the transplanted tissue. Although such studies do not pose risk to human subjects, they pose unique ethical challenges concerning the previous wishes of the deceased, rights of surviving family members, effective operation and fair distribution of medical services, and public transparency. This article investigates the ethical, legal and social considerations in performing engineered organ research on the recently deceased.
PMID: 31563872
ISSN: 1473-4257
CID: 4115892

Education Research: Teaching and assessing communication and professionalism in neurology residency with simulation

Kurzweil, Arielle M; Lewis, Ariane; Pleninger, Perrin; Rostanski, Sara K; Nelson, Aaron; Zhang, Cen; Zabar, Sondra; Ishida, Koto; Balcer, Laura J; Galetta, Steven L
PMID: 31959708
ISSN: 1526-632x
CID: 4272802

Discontinuation of postoperative prophylactic antibiotics for endoscopic endonasal surgery [Meeting Abstract]

Benjamin, C G; Dastagirzada, Y; Bevilacqua, J; Gurewitz, J; Sen, C; Golfinos, J G; Placantonakis, D; Jafar, J J; Lebowtiz, R; Lieberman, S; Lewis, A; Pacione, D
Direct access through the sinuses and nasopharyngeal mucosa in the endoscopic endonasal approach (EEA) raises concern for a contaminated operative environment and subsequent infection. The reported rate of meningitis in endoscopic endonasal skull base surgery in the literature ranges from 0.7 to 3.0% [1, 2]. The only factor identified as being independently associated with meningitis in a statistically significant manner is cerebrospinal fluid (CSF) leak [1-5]. However, many centers performing high volume of EEAs use postoperative antibiotic coverage independent of the presence intraoperative or postoperative CSF leak. Furthermore, while meningitis remains a severe concern, most centers use postoperative gram-positive coverage to prevent toxic shock syndrome caused by Staphylococcus aureus infection in the setting of prolonged nasal packing. There are currently a multitude of approaches regarding perioperative antibiotic coverage in EEAs [1-4]. Given the lack of consensus in the literature and our experience regarding the benefit of discontinuation of prolonged prophylactic antibiotics throughout the breadth of neurosurgical procedures, we sought to analyze the need for postoperative antibiotics in EEAs further. As such, we performed a prospective analysis compared with a retrospective cohort to delineate whether discontinuation of postoperative antibiotics leads to a change in the rate of postoperative infections. The retrospective cohort consisted of patients who underwent an EEA from January 1, 2013 to May 31, 2019. These patients all received postoperative antibiotics while nasal packing was in place (median 7 days). Starting on April 1, 2019 until August 1, 2019, we discontinued postoperative antibiotic use. Patients from this group made up the prospective cohort. The retrospective cohort had 315 patients (66% pituitary macroadenomas vs. 7% microadenomas, 4% meningiomas, 4% craniopharyngiomas, 4% chordomas, and 15% others) while the prospective group had 23 patients (57% pituitary macroadenomas, 30% craniopharyngiomas, 8% meningiomas/chordomas, and 5% others). The primary endpoint was rate of postoperative infections and specifically, meningitis and multidrug resistant organism (MDRO) infections. There was no statistically significant difference in the use of nasal packing (p = 0.085), intraoperative CSF leak (p = 0.133), and postoperative CSF leak (p = 0.507) between the two groups. There was also no significant difference in the number of patients with positive preoperative MSSA and MRSA nasal swabs (p = 0.622). There was a significant decrease in the number of patients discharged with antibiotics (55.1% in the retrospective and 4.5% in the prospective group, p = 0.000). The number of patients with positive blood cultures (p = 0.701) and positive urine cultures (p = 0.691) did not differ significantly between the two groups. Finally, there was no statistically significant difference in postoperative CSF infections (p = 0.34) or MDRO infections (0.786) between the two groups. We describe promising preliminary results that demonstrate that discontinuation of postoperative antibiotics in EEAs do not lead to a statistically significant increase in the rate of postoperative CSF or MDRO infections. The previous algorithm for postoperative antibiotic coverage in our center, like many centers, called for gram-positive coverage, which may have contributed to the overall preponderance of gram-negative meningitis cases in this cohort
EMBASE:631114231
ISSN: 2193-6331
CID: 4387132

It's Time to Revise the Uniform Determination of Death Act

Lewis, Ariane; Bonnie, Richard J; Pope, Thaddeus
PMID: 31869833
ISSN: 1539-3704
CID: 4244052

High-Dose 4-Factor Prothrombin Complex Concentrate for Warfarin-Induced Intracranial Hemorrhage

Merchan, Cristian; Ahuja, Tania; Raco, Veronica; Lewis, Ariane
Background and Purpose/UNASSIGNED:The ideal dosing regimen of 4-factor prothrombin complex concentrate (4FPCC) after warfarin-induced intracranial hemorrhage (WICH) remains unclear. We sought to compare the safety and efficacy of the 4FPCC package insert dosing strategy (standard dose [SD]) with our institutional guideline for high-dose (HD) 4FPCC for patients with WICH. Methods/UNASSIGNED:We compared the percentage of SD and HD patients who achieved an international normalized ratio (INR) ≤1.3 at a single institution between January 2014 and July 2017. Additionally, we assessed hematoma expansion, recurrence of INR > 1.3, and occurrence of thrombotic events within 7 days of 4FPCC administration. Results/UNASSIGNED:= .243). Conclusions/UNASSIGNED:High-dose 4FPCC appears to be more effective at lowering INR and preventing bleed expansion in patients with WICH, while maintaining a similar safety profile.
PMCID:6900656
PMID: 31839860
ISSN: 1941-8744
CID: 4243452

Requests for somatic support after neurologic death determination: Canadian physician experiences (November, 10.1007/s12630-020-01852-9, 2020) [Correction]

van Beinum, Amanda; Healey, Andrew; Chandler, Jennifer; Dhanani, Sonny; Hartwick, Michael; Lewis, Ariane; Marshall, Calista; Marshall, Jocasta; Shemie, Sam; Singh, Jeffrey M.
ISI:000592132100003
ISSN: 0832-610x
CID: 4729012

SARS-CoV-2 Is Not Detected in the Cerebrospinal Fluid of Encephalopathic COVID-19 Patients

Placantonakis, Dimitris G; Aguero-Rosenfeld, Maria; Flaifel, Abdallah; Colavito, John; Inglima, Kenneth; Zagzag, David; Snuderl, Matija; Louie, Eddie; Frontera, Jennifer Ann; Lewis, Ariane
Neurologic manifestations of the novel coronavirus SARS-CoV-2 infection have received wide attention, but the mechanisms remain uncertain. Here, we describe computational data from public domain RNA-seq datasets and cerebrospinal fluid data from adult patients with severe COVID-19 pneumonia that suggest that SARS-CoV-2 infection of the central nervous system is unlikely. We found that the mRNAs encoding the ACE2 receptor and the TMPRSS2 transmembrane serine protease, both of which are required for viral entry into host cells, are minimally expressed in the major cell types of the brain. In addition, CSF samples from 13 adult encephalopathic COVID-19 patients diagnosed with the viral infection via nasopharyngeal swab RT-PCR did not show evidence for the virus. This particular finding is robust for two reasons. First, the RT-PCR diagnostic was validated for CSF studies using stringent criteria; and second, 61% of these patients had CSF testing within 1 week of a positive nasopharyngeal diagnostic test. We propose that neurologic sequelae of COVID-19 are not due to SARS-CoV-2 meningoencephalitis and that other etiologies are more likely mechanisms.
PMCID:7759491
PMID: 33362695
ISSN: 1664-2295
CID: 4731452

Determination of Death by Neurologic Criteria in the United States: The Case for Revising the Uniform Determination of Death Act

Lewis, Ariane; Bonnie, Richard J; Pope, Thaddeus; Epstein, Leon G; Greer, David M; Kirschen, Matthew P; Rubin, Michael; Russell, James A
Although death by neurologic criteria (brain death) is legally recognized throughout the United States, state laws and clinical practice vary concerning three key issues: (1) the medical standards used to determine death by neurologic criteria, (2) management of family objections before determination of death by neurologic criteria, and (3) management of religious objections to declaration of death by neurologic criteria. The American Academy of Neurology and other medical stakeholder organizations involved in the determination of death by neurologic criteria have undertaken concerted action to address variation in clinical practice in order to ensure the integrity of brain death determination. To complement this effort, state policymakers must revise legislation on the use of neurologic criteria to declare death. We review the legal history and current laws regarding neurologic criteria to declare death and offer proposed revisions to the Uniform Determination of Death Act (UDDA) and the rationale for these recommendations.
PMID: 31955689
ISSN: 1748-720x
CID: 4273752

Objective Structured Clinical Exams (OSCE) are a feasible method of teaching how to discuss a nonepileptic seizure diagnosis

Valentine, David; Kurzweil, Arielle; Zabar, Sondra; Lewis, Ariane
OBJECTIVE:Presenting the diagnosis of psychogenic nonepileptic seizures (PNES) can be a difficult task, but disclosing this information effectively is important to optimize patient outcomes. We sought to develop a standardized method to teach neurology residents how to introduce the diagnosis of PNES via an objective structured clinical examination (OSCE) with a standardized patient (SP). METHODS:In conjunction with the New York University School of Medicine Simulation Center (NYSIM), we designed an OSCE in which a resident had to inform a SP of her diagnosis of PNES and discuss a treatment plan. The SP was provided with details to gradually disclose depending on what the resident said about the history of her episodes, triggers for her episodes and her history of sexual abuse. Each encounter was observed by an attending physician who provided real-time feedback to the resident after the session. Additionally, the SP completed an objective written checklist of items the resident should have covered in the session and gave them verbal feedback. RESULTS:Twenty-six adult neurology (n = 22), child neurology (n = 3), and neuropsychiatry (n = 1) residents participated in this OSCE in 2018 and 2019, with full data available for 25 participants. Residents reported the OSCE was very useful (mean Likert score of 4.9/5). They felt moderately prepared (mean Likert score 3.8/5) and rated their performance as a mean of 3.3/5. On the SP's checklist, most residents were rated as Well Done in the domains of information gathering, relationship development, and education and counseling. Only in the domain of psychosocial assessment were most residents rated as Not Done (only 7/25 inquired about past trauma as a risk factor for PNES). SIGNIFICANCE/CONCLUSIONS:The OSCEs are a feasible and useful way to teach neurology residents about discussing PNES, as they allow for provision of real-time practice and feedback in a safe environment without real patients.
PMID: 31654939
ISSN: 1525-5069
CID: 4153492

A Survey of Multidenominational Rabbis on Death by Neurologic Criteria

Lewis, Ariane
OBJECTIVE:(1) Determine the pervasiveness of the belief that brain death/death by neurologic criteria (BD/DNC) is not death among rabbis. (2) Examine rabbinic beliefs about management after BD/DNC. METHODS:An electronic anonymous survey about BD/DNC determination and management after BD/DNC was created and distributed to members of the Central Conference of American Rabbis (the Reform Rabbinic leadership organization), the Rabbinic Council of America (an Orthodox organization), the Rabbinic Assembly (a Conservative organization), and the Reconstructionist Rabbinic Association. RESULTS:Ninety-nine rabbis (40 Reform, 32 Orthodox, 22 Conservative, and 5 Reconstructionist) completed the survey. Awareness of the requirements for BD/DNC was poor (median of 33% of the requirements correctly identified [interquartile range of 22-66%]), but 81% of rabbis knew that absence of heartbeat is not required for BD/DNC. Although only 5% of all rabbis believed a person who is brain dead could recover, 22% did not believe BD/DNC is death, and 18% believed mechanical ventilation should be continued after BD/DNC. There was a significant relationship between denomination and belief that: (1) a person who is brain dead can recover (p = 0.04); (2) a person who is brain dead is dead (p < 0.001); (3) mechanical ventilation should be continued after BD/DNC (p < 0.001); (4) hydration should be continued after BD/DNC (p = 0.002); (5) nutrition should be continued after BD/DNC (p < 0.001); (6) medications to support blood pressure should be continued after BD/DNC (p < 0.001); and (7) cardiopulmonary resuscitation should be performed when a brain dead person's heart stops (p = 0.006). CONCLUSIONS:Rabbinic knowledge about the intricacies of BD determination is poor. Rabbinic perspectives on management after BD/DNC vary. These empirical data on rabbinic perspectives about BD/DNC may be helpful when considering accommodation of religious objections to BD/DNC.
PMID: 31218638
ISSN: 1556-0961
CID: 3939262