Proliferative Typhlocolitis With Multinucleated Giant Cells: A Nonspecific Enteropathy in Immunodeficient Sentinel Mice.

Beginning in 2015, athymic nude sentinel mice from conventional, medium-, and high-security facilities presented to the Comparative Pathology Laboratory (CPL) with weight loss, diarrhea, and/or rectal prolapse. Regardless of whether clinical signs were present or absent, the gross observation of ceco-colonic thickening corresponded histologically to pleocellular typhlocolitis with mucosal hyperplasia and lamina proprial multinucleated cells. A subset of affected sentinels exhibited granulomatous serositis and hepatosplenic necrosis with multinucleated cells. Initial suspicion of mouse hepatitis virus infection was excluded by polymerase chain reaction, electron microscopy, and serology. Multinucleated giant cells were confirmed as macrophages by positive immunoreactivity to Mac-3 and Iba-1 and negative immunoreactivity to pancytokeratin. From conventional and medium-security facilities, Helicobacter species were identified in 40 of 143 (27.9%) mice, with H. hepaticus accounting for 72.5% of identified Helicobacter species. Other agents included opportunistic bacterial infection (41/145, 28.3%), murine norovirus (16/106, 15.1%), and pinworms (2/146, 1.4%). From high-security facilities, only Enterobacter cloacae was identified (2/13, 15.4%), and no evidence of Helicobacter sp., murine norovirus, or pinworms was present. No potentially infectious disease agent(s) was identified in 71 of 146 (48.6%) affected nude sentinels from conventional and medium-security facilities and 11 of 13 (84.6%) affected nude sentinels from high-security facilities. No statistically significant differences in histologic lesion scores were identified between Helicobacter-positive and Helicobacter-negative mice. Thus, proliferative typhlocolitis with multinucleated giant cells was considered a nonspecific histologic pattern associated with a variety of primary and opportunistic pathogens in athymic nude mice.

The Work of ASBH's Clinical Ethics Consultation Affairs Committee: Development Processes Behind Our Educational Materials.

The authors of this article are previous or current members of the Clinical Ethics Consultation Affairs (CECA) Committee, a standing committee of the American Society for Bioethics and Humanities (ASBH). The committee is composed of seasoned healthcare ethics consultants (HCECs), and it is charged with developing and disseminating education materials for HCECs and ethics committees. The purpose of this article is to describe the educational research and development processes behind our teaching materials, which culminated in a case studies book called A Case-Based Study Guide for Addressing Patient-Centered Ethical Issues in Health Care (hereafter, the Study Guide). In this article, we also enumerate how the Study Guide could be used in teaching and learning, and we identify areas that are ripe for future work.

Navigating Clinical Ethics: Using Real Case Constellations to Guide Learners and Teachers in Medicine.

Case-based learning is a staple of clinical ethics education in medicine. The sources for medical educators generally are lengthy case books or single, often rare, case analyses in the literature. Busy clinicians may not have the time or inclination to sift through case books to find suitable teaching material, and the latter present unusual cases that many physicians may never encounter in their own practice. Relatively few articles present multiple cases involving ethical issues that are likely to appear in everyday practice in an accessible format for teaching. To fill this gap, we developed a series of paradigmatic cases based on the recurrent themes we identified through a systematic analysis of our clinical ethics consultations in a 5-year period and our collective clinical ethics judgment. We constructed four amalgam "bread-and-butter" ethics cases that are not overly service specific and can be used in medical and residency education along with specific questions for discussion. Topics include decision-making capacity, withholding and withdrawing life-sustaining treatment, patient wishes and do not resuscitate orders, and brain death. Our objective was to help a range of residents and other physicians become more confident and facile in identifying and addressing recurrent ethical issues in their practice.

What Ethical Issues Really Arise in Practice at an Academic Medical Center? A Quantitative and Qualitative Analysis of Clinical Ethics Consultations from 2008 to 2013.

As the field of clinical ethics consultation sets standards and moves forward with the Quality Attestation process, questions should be raised about what ethical issues really do arise in practice. There is limited data on the type and number of ethics consultations conducted across different settings. At Loyola University Medical Center, we conducted a retrospective review of our ethics consultations from 2008 through 2013. One hundred fifty-six cases met the eligibility criteria. We analyzed demographic data on these patients and conducted a content analysis of the ethics consultation write-ups coding both the frequency of ethical issues and most significant, or key, ethical issue per case. Patients for whom ethics consultation was requested were typically male (55.8 %), white (57.1 %), between 50 and 69 years old (38.5 %), of non-Hispanic origin (85.9 %), and of Roman Catholic faith (43.6 %). Nearly half (47.4 %) were in the intensive care unit and 44.2 % died in the hospital. The most frequent broad ethical categories were decision-making (93.6 %), goals of care/treatment (80.8 %), and end-of-life (73.1 %). More specifically, capacity (57.1 %), patient's wishes/autonomy (54.5 %), and surrogate decision maker (51.3 %) were the most frequent particular ethical issues. The most common key ethical issues were withdrawing/withholding treatment (12.8 %), patient wishes/autonomy (12.2 %), and capacity (11.5 %). Our findings provide additional data to inform the training of clinical ethics consultants regarding the ethical issues that arise in practice. A wider research agenda should be formed to collect and compare data across institutions to improve education and training in our field.

Developing an Evaluation Tool for Assessing Clinical Ethics Consultation Skills in Simulation Based Education: The ACES Project.

The American Society for Bioethics and Humanities has created a quality attestation (QA) process for clinical ethics consultants; the pilot phase of reviewing portfolios has begun. One aspect of the QA process which is particularly challenging is assessing the interpersonal skills of individual clinical ethics consultants. We propose that using case simulation to evaluate clinical ethics consultants is an approach that can meet this need provided clear standards for assessment are identified. To this end, we developed the Assessing Clinical Ethics Skills (ACES) tool, which identifies and specifies specific behaviors that a clinical ethics consultant should demonstrate in an ethics case simulation. The aim is for the clinical ethics consultant or student to use a videotaped case simulation, along with the ACES tool scored by a trained rater, to demonstrate their competence as part of their QA portfolio. The development and piloting of the tool is described.

Safety, efficacy and efficiency of laser-assisted IVF in subfertile mutant mouse strains.

In the present report we studied the safety, efficacy and efficiency of using an infrared laser to facilitate IVF by assessing fertilization, development and birth rates after laser-zona drilling (LZD) in 30 subfertile genetically modified (GM) mouse lines. We determined that LZD increased the fertilization rate four to ten times that of regular IVF, thus facilitating the derivation of 26 of 30 (86.7%) GM mouse lines. Cryopreserved two-cell stage embryos derived by LZD-assisted IVF were recovered and developed to blastocysts in vitro at the same rate as frozen-thawed embryos derived by regular IVF. Surprisingly after surgical transfer to pseudopregnant recipients the birth rate of embryos derived by LZD-assisted IVF was significantly lower than that of embryos derived by regular IVF. However this result could be completely mitigated by the addition of 0.25 M sucrose to the culture medium during LZD which caused the oocyte to shrink in volume relative to the perivitelline space. By increasing the distance from the laser target site on the zona pellucida, we hypothesize that the hyperosmotic effect of sucrose reduced the potential for laser-induced cytotoxic thermal damage to the underlying oocytes. With appropriate preparation and cautious application, our results indicate that LZD-assisted IVF is a safe, efficacious and efficient assisted reproductive technology for deriving mutant mouse lines with male factor infertility and subfertility caused by sperm-zona penetration defects.

Putting ethics and clinical decision making before politics: requiring COVID-19 immunization for Solid Organ Transplantation (SOT) Candidates and their Support Team.

We recommend that vaccination for COVID-19 should be a requirement for waitlist activation for solid organ transplant (SOT). We also recommend that such vaccination be required of the primary member of the in-home support team. We argue that these requirements are consistent with current standard practices that draw on a well-established ethical framework. As a result, these recommendations should be easily received and are only controversial owing to the inflamed and politicized state of public discourse.

"We Have a Lot of Power ": A Medical School's Journey Through Its New Deferred Action for Childhood Arrivals (DACA) Initiative.

Purpose To describe and analyze qualitatively the impact of implementing the "Stritch Deferred Action for Childhood Arrivals (DACA) Initiative" (SDI) at the Stritch School of Medicine (SSOM), Loyola University, Chicago in 2012. The SDI is a three-step process that included: 1) opening the Stritch admissions policy to welcome DACA students to apply, 2) evaluating DACA applicants equitably with all other applicants, and 3) seeking funding to enable these students to matriculate.  Method Focus groups and in-depth interviews were conducted to explore DACA and non-DACA students' experience of the SDI on their medical school journey and the institutional culture. During the study (in 2017-18), the medical school year (M)1-M3 cohorts included DACA students, while the M4 class did not. A grounded theory method was used to summarize and analyze qualitative data. Results Four major themes and 11 subthemes emerged from the data analysis. "Beliefs and Attitudes" included the subthemes of motivation to become physicians, resilience, and the mission and values of individuals and the institution. Students noted "obstacles" in reaching medical school, along with those they encountered within it. They also noted multiple "opportunities" presented through the SDI and the importance of mentors and allies. Lastly, the "impact" of the SDI on individuals, the institution, and the wider community was discussed by participants. Conclusion Enacting the SDI enabled cohorts of DACA recipients to matriculate at SSOM. Both DACA and non-DACA students in this study identified the importance of including these students as future physicians and articulated the impact of this change on them, their classmates, the institution, and the community as solidarity was formed and students' awareness of their power as future physicians to advocate for underserved populations developed.

What Is the Minimal Competency for a Clinical Ethics Consult Simulation? Setting a Standard for Use of the Assessing Clinical Ethics Skills (ACES) Tool.

Background: The field of clinical ethics is examining ways of determining competency. The Assessing Clinical Ethics Skills (ACES) tool offers a new approach that identifies a range of skills necessary in the conduct of clinical ethics consultation and provides a consistent framework for evaluating these skills. Through a training website, users learn to apply the ACES tool to clinical ethics consultants (CECs) in simulated ethics consultation videos. The aim is to recognize competent and incompetent clinical ethics consultation skills by watching and evaluating a videotaped CEC performance. We report how we set a criterion cut score (i.e., minimally acceptable score) for judging the ability of users of the ACES tool to evaluate simulated CEC performances. Methods: A modified Angoff standard-setting procedure was used to establish the cut score for an end-of-life case included on the ACES training website. The standard-setting committee viewed the Futility Case and estimated the probability that a minimally competent CEC would correctly answer each item on the ACES tool. The committee further adjusted these estimates by reviewing data from 31 pilot users of the Futility Case before determining the cut score. Results: Averaging over all 31 items, the proposed proportion correct score for minimal competency was 80%, corresponding to a cut score that is between 24 and 25 points out of 31 possible points. The standard-setting committee subsequently set the minimal competency cut score to 24 points. Conclusions: The cut score for the ACES tool identifies the number of correct responses a user of the ACES tool training website must attain to "pass" and reach minimal competency in recognizing competent and incompetent skills of the CECs in the simulated ethics consultation videos. The application of the cut score to live training of CECs and other areas of practice requires further investigation.

Fatal disseminated encephalitozoonosis in a captive, adult Goeldi's monkey (Callimico goeldii) and subsequent serosurvey of the exposed conspecifics.

A captive, adult male Goeldi's monkey (Callimico goeldii) (GM) presented in acute respiratory distress 4 yr after importation into the United States from Europe. Radiographs and echocardiogram were consistent with heart failure. The monkey died within 24 hr of presentation. Necropsy findings included multicentric arteritis and aortitis with aneurysm associated with microsporidian organisms morphologically consistent with Encephalitozoon species. Polymerase chain reaction confirmed organisms were Encephalitozoon cuniculi. Sequence analysis of amplicons generated by using primers specific for the polar tube protein of E. cuniculi determined the organism to be genotype II. An E. cuniculi serosurvey of potentially exposed conspecifics that represented approximately 40% of the captive GM population in the United States was conducted. Multiple individuals that had been imported from Europe with the individual of this report were seropositive via an immunofluorescent antibody assay for E. cuniculi. Multiple samples were available from 3 individuals that demonstrated a decrease in titer or reversion to seronegative status within 3 yr of initial positive status. All other GM were negative on serology. This case is unique in that the genotype identified (genotype II) was different than the genotype (genotype III) reported in other New World primate (NWP) species, the patterns of arteritis were different from the typical pattern of microsporidial vasculitis described in other species, and clinical disease was observed in an adult. Most reported cases of clinical disease secondary to E. cuniculi in NWP have been in neonates and juveniles.

Retrospective Analysis of Reproductive Performance of Pair-bred Compared with Trio-bred Mice.

Federal guidelines provide recommendations regarding the minimum of floor space that should be allotted for breeding laboratory rodents. Mouse mating systems used by a variety of institutions frequently deviate from these recommendations. Regulatory agencies suggest that deviations from established guidelines should be assessed on an institutional basis and recommend periodic review by the local IACUC. Mouse breeding data, collected in a laboratory animal management software program at a single institution, were retrospectively analyzed to determine the effects of 2 breeding schemes on reproductive performance. Data were analyzed over a 20-mo period from all inbred strains of mice breeding in the vivarium. Variables included total number of pups per litter, pups per female, and litters per female. Data indicated that the numbers of pups and litters per dam do not differ between trio-bred (one male, 2 female) and pair-bred (one male, one female) mice. However, more pups were weaned per litter in trio-bred (mean, 5.8 pups) when-compared with pair-bred (mean, 4.7 pups) mice. These results suggest that allocating less than the recommended amount of floor space is not detrimental to the overall breeding success of the strains of mice examined.