Immunomodulatory Therapies for COVID-19 in Solid Organ Transplant Recipients

Purpose of Review Severe coronavirus disease 2019 (COVID-19) is characterized by the development of a deleterious hyperinflammatory response, in which the pleiotropic cytokine interleukin (IL)-6 plays a pivotal role. The administration of immunomodulatory therapies has been proposed to revert the tissue damage induced by COVID-19-related cytokine release syndrome (CRS). The present review summarizes the biological rationale and available clinical experience with this therapeutic strategy in the specific scenario solid organ transplantation (SOT). Recent Findings A number of case reports, case series, and non-controlled cohort studies have assessed the efficacy and safety of the anti-IL-6-receptor monoclonal tocilizumab in SOT (namely kidney transplantation) recipients with COVID-19 pneumonia and CRS. Although the heterogeneity in patient management and the lack of a control group limit the interpretation of these results, tocilizumab therapy appears to provide some clinical benefit in post-transplant COVID-19 and to be reasonably safe in terms of bacterial superinfection. A large randomized clinical trial (RCT) has shown survival benefit with adjuvant corticosteroids in non-transplant patients, but supporting evidence is scarce for SOT recipients and confounded by the variable adjustment of baseline immunosuppression. Anecdotal experiences have been reported with the use of the anti-IL-1 agent anakinra and the NLRP3 inflammasome inhibitor colchicine in this population. Summary Immunomodulation has emerged as a promising option for SOT recipients with COVID-19-related CRS, with available experience mainly restricted to the anti-IL-6 agent tocilizumab. However, the supporting evidence is scarce and of low quality. In the absence of RCT, observational studies including well-matched control groups should be designed in future.

Fluid administration rate for uncontrolled intraabdominal hemorrhage in pigs

ABSTRACTBackgroundWe hypothesized that slow crystalloid resuscitation would improve blood loss and hemoglobin compared to a rapid resuscitation during uncontrolled hemorrhage.MethodsAnesthetized, splenectomized domestic swine underwent hepatic lobar hemitransection. Lactated Ringers was given at 150 or 20 mL/min IV (rapid vs. slow, respectively, N = 12 per group; limit of 100 mL/kg). Vital sign monitoring and serum testing was done for up to 180 min, followed by necropsy.ResultsSurvival was 7 vs. 8 out of 12 subjects, rapid vs. slow respectively (p>0.05). The slow group had a less blood loss (1.6 vs. 2.7 L, respectively) and a higher final hemoglobin concentration (6.0 vs. 3.4 g/dL).ConclusionsUsing a fixed volume of crystalloid resuscitation in this porcine model of uncontrolled intraabdominal hemorrhage, a slow IV infusion rate produced less blood loss and a higher hemoglobin level compared to rapid infusion.

When Is Patient Education Unethical?

Although patient education is central to the ethical practice of nursing, it can be practiced in an ethically contested or unethical way. It is sometimes used to: forward a societal goal the individual might not have chosen; assume that patients should learn to accommodate unjust treatment; exclude the views of all except the dominant health care provider group; limit the knowledge a patient can receive; make invalid or unreliable judgments about what a patient can learn; or require a patient to change his or her identity to meet a medical ideal. Both health promotion education and manipulating patient beliefs in situations of uncertainty are ethically contested. Nussbaum's capabilities approach is used here as a moral framework through which to view the goals and practice of patient education. This provides better guidance than the current conception of patient education as an instrument to carry out the directives of medical practice.