Hayley A. Gans

Background: Solid Organ Transplant ( SOT ) provides a survival advantage for individuals with end organ failure. Little is known about the specific effects of immunosuppression on the competence of the immune system during the post‐transplant period especially in the pediatric population, and current immunosuppression and prophylaxis practices are not well informed by immune data. Methods: Blood samples from pediatric patients < 18 years old were collected prior to and 6‐ and 12 months after liver transplant. Peripheral blood mononuclear cells ( PBMCs ) were stimulated with PMA /Ionomycin and the phenotype and function of T cell subsets and NK cells were systematically characterized using cytometry by time‐of‐flight ( CyTOF ). Results: In a cohort of 4 pediatric liver transplant patients, levels of CD4 + and CD8 + T cells, Tregs and NK cells at 6‐ and 12 months following liver transplant were similar to levels before transplant. Upon stimulation, pro‐inflammatory, antiviral, and inhibitory T cell cytokines and enzymes were not reduced at 6 months post‐transplant and remained stable at 12 months. IL ‐2 production, a tacrolimus target, from CD4 + and CD8 + T cells did not correlate with tacrolimus levels. Conclusion: T cell function was not reduced by 6 months following liver transplant. This suggests that it might be safe to discontinue viral prophylaxis or initiate vaccinations sooner than previously suspected. Tregs functional marker expression was intact by 6 months post‐transplant suggesting lower risk of rejection in this cohort. Tacrolimus level may not be a good indication for immunocompetence and T cell functional assays may be more predictive of susceptibility to infection.

The global burden of acute lower respiratory tract infections, including viral etiologies, equated to 725 557 deaths in 2021 in children under 4 years of age. Community‐acquired respiratory viral infections (RVI) also carry a high burden among pediatric solid organ transplant recipients (PSOTR), accounting for 14.5% of hospitalizations in the first year post‐transplant in an American cohort. This mini review on behalf of the International Pediatric Transplant Association (IPTA) infectious diseases committee discusses novel preventative and prophylactic strategies and includes pertinent updates for vaccine‐preventable RVI including influenza, SARS‐CoV‐2, and RSV in PSOTR.

Background: Although adult transplant centers are successfully transplanting organs from hepatitis C virus (HCV)‐infected donors with detectable viral load by nucleic acid testing (NAT+) into HCV‐negative recipients, this practice has not yet been adopted widely by the pediatric heart transplant community.Methods: We present a case series of four patients who received heart transplants from HCV NAT+ donors at a pediatric transplant center, including two pediatric patients < 18 years of age.Results: All recipients tolerated a 12‐week course of glecaprevir/pibrentasvir and achieved a sustained virologic response with no HCV or liver complications with over 1 year of follow‐up (range 1.4–2.5 years). All four have had good post‐heart transplant outcomes with normal graft function and good functional status without rejection or cardiac allograft vasculopathy at time of last follow‐up.Conclusions: This case series details the successful multidisciplinary implementation of a protocol to accept cardiac allografts from HCV NAT+ donors for transplantation into HCV negative recipients at our pediatric transplant center. With the limited donor pool in pediatrics and the morbidity associated with prolonged durations on the transplant waitlist, pediatric centers should consider utilizing organs from HCV NAT+ donors to broaden the donor pool. Future work should evaluate other organs beyond heart and optimal timing and duration of direct acting antiviral therapy.

While the pediatric subspecialty applicant pool is increasing, so is the number of open positions, with an overall 1:1 ratio of applicant to position. Unfortunately, there is a wide disparity in this ratio dependent upon subspecialty, leaving many programs unfilled.1 Since 2020, recruitment has shifted to virtual, and while the impact on programs and applicants is not fully understood, some program leadership feel disadvantaged without the opportunity to showcase their programs in person. To satisfy the growing desire for pediatric subspecialty programs to be more visible to the applicant pool, a national virtual recruitment session was piloted for pediatric subspecialties using the virtual format created by FuturePedsRes.Individual subspecialty recruitment sessions were held during July 2022 from 8:00-9:30 pm ET featuring 2 to 3 subspecialties on 4 different dates. Prior to the evening, programs were given the option to post a slide on the Association of Pediatric Program Directors website describing their fellowship training program for applicant review. A representative for each participating subspecialty, identified through the Council of Pediatric Subspecialties, served as the communication director between programs and session organizers to coordinate logistics prior to the event. Each subspecialty had a unique virtual link on the night of their session, and each fellowship program within that subspecialty had an individual breakout room. Applicants rotated freely between program breakout rooms, with a suggestion to rotate every 10 minutes. A post-participation survey was sent to all participants.Eleven pediatric subspecialties participated, including 701 live participants representing programs and applicants (Table). Of the participating program leadership, 158 completed a post-participation survey, with half indicating the session increased the visibility of their program, several citing an appreciation of the intimate relationship with the applicants, and a majority wanting to participate again. Of the 49 applicants who responded to the survey, 100% felt the evening was a good use of their time, highlighting the face time with leadership and trainees and the opportunity to meet many programs in one setting as positives. Importantly, 92% (45 of 49) of applicants visited programs outside their current geographic location, 51% (25 of 49) visited programs they were not originally planning to apply to, and 42% (18 of 43) applied to new programs as a result of participating in the session. Challenges identified included: some programs having no applicants visit their breakout rooms, the late timing of sessions in this recruitment season, and some logistical issues during the sessions.The inaugural national pediatric subspecialty recruitment sessions were successful, resulting in increased visibility for programs and in applicants applying to programs they had not considered prior to the session. Applicants thought the accessibility of all programs on one platform simultaneously was helpful, and many visited programs they otherwise would not have had the opportunity to explore. In response to feedback, several logistical changes will be applied to subsequent sessions for the 2023 appointment year, including a shift to earlier in the year, prior to the submission of applications. This will allow for increased time for advertising the sessions and improved promotion of individual program information in advance. This model of training program informational sessions is applicable across graduate medical education programs and may serve to not only provide enhanced individual program visibility but also increase awareness about careers in subspecialities in general and potentially expand the applicant pool.

To truly build an equitable health care system, we need a diverse physician workforce that reflects the demographics of the general population. Diversity improves clinical care outcomes, improves patient satisfaction, and is associated with improved treatment adherence when patients are treated by race-concordant physicians. Additionally, Black, Indigenous, and Hispanic/Latinx physicians are more likely to focus their care efforts on the most vulnerable patient populations in the United States.1 A sense of urgency has developed as recent trends show a decreasing proportion of underrepresented in medicine (UIM) pediatric subspecialty fellows.2,3 The drivers causing this workforce issue have not been fully identified, with limited exposure to subspecialty experiences as a potential contributor. Increasing the numbers of UIM physicians requires deliberate action by academic institutions to recruit and support UIM applicants across various medical subspecialties.The Promoting Resident Experiences in the Subspecialties at Stanford (PRESS) program is a 4-week funded and mentored pediatric subspecialty rotation for UIM residents who will be applying for subspecialty fellowship in the next year. PRESS was created with the following goals: (1) to increase recruitment of UIM trainees into pediatric subspecialty fellowships and academic medicine; (2) to improve inclusion, belonging, and career development of the next generation of UIM subspecialists through coaching and mentoring; and (3) to enhance our learning community by increasing the diversity among our trainees and institution, both during the rotation and afterward. Visiting residents self-select a subspecialty experience, are assigned a faculty mentor and a fellow mentor within the division, and are invited to events within the division, the department, and the larger graduate medical education community. They receive individualized mentorship and coaching on creating a CV and personal statement as well as strategies to increase success in the fellowship application process. Each resident receives funding to cover travel and living expenses during the rotation.Our inaugural cohort consisted of 5 residents. Our residents identified as African American/Black, Hispanic/Latinx, Asian, and North African, and hailed from 4 different states. Our second cohort will include 7 residents (37% acceptance rate), identifying as African American/Black, Hispanic/Latinx, and Southeast Asian, coming from 4 different states.A survey of the first cohort determined that all residents (100%) found the program to be valuable, offering a unique experience and a network of colleagues in and out of their chosen subspecialty. All residents stated that participation in the PRESS program encouraged them to apply to our institution when they would not have otherwise. All residents found the mentorship and individualized coaching helpful. One resident remarked: “It was an absolutely invaluable experience and nothing I probably would have gotten to experience on my own. The support and mentorship was great and I loved the desire for change. I would love for other UIM to experience medicine at an elite center…and I've already recommended that several people I know apply for next year.”Program leadership and residents cited the program as an effective recruiting tool, and leaders felt the PRESS program allowed them to consider applicants that they might not have otherwise. As one fellowship leader highlighted, there is the benefit of “participating in developing opportunities for exposure/recruitment of UIM trainees, [and the] ability to gain new perspectives.” Excitedly, one resident from our inaugural cohort matched into the pediatric cardiology fellowship at our institution. All other residents matched into their desired specialties.The PRESS program represents a feasible and effective program to expose and recruit UIM trainees into programs they would not have otherwise considered and to help them develop a sense of belonging in their subspecialty. It may also help fellowship programs and institutions expand their recruitment base, encouraging a more diverse applicant pool.

Background: Solid organ transplant (SOT) recipients are at increased risk of vaccine‐preventable illness due to the high degree of immunosuppression required following transplantation. The current recommendation is to vaccinate with live attenuated vaccines, including Measles, Mumps, and Rubella (MMR) and Varicella (VAR) vaccines, at least 4 weeks prior to transplant. However, data to support the time interval between vaccine and transplant are limited.Methods: We conduct a literature review of the natural history of the viruses and length of viremia following live‐attenuated viral vaccines, and we describe a series of 5 cases from 2 pediatric transplant centers in which live attenuated viral vaccines were administered within 21 days prior to SOT.Results: None of the 5 children who received MMR or VAR 8‐21 days prior to liver (2) and heart (3) transplant suffered from vaccine‐related viral illness after transplant, even in the presence of significant immunosuppression with T‐cell‐depleting agents.Conclusion: These cases support that shorter intervals of live vaccine administration prior to transplant may be safe, allowing the vaccination of a larger cohort of SOT candidates. Increasing pretransplant vaccinations is crucial since, in most cases, live viral vaccines are contraindicated posttransplantation, and the most effective vaccine approaches utilize prime‐boost strategies, priming before and boosting after transplant.

Background: Immunocompromised children and adults are at increased risk for severe disease and death following varicella zoster virus infection. Varicella zoster immune globulin (human) (VARIZIG) is recommended for post-exposure prophylaxis to prevent or attenuate varicella infection in high-risk individuals.Methods: An open-label, expanded-access program provided VARIZIG to high-risk individuals exposed to varicella or herpes zoster. Immunocompromised participants were stratified by type of immunocompromising condition (“oncologic immunodeficiency”, “primary immunodeficiency”, “solid organ transplant” [SOT], “hematopoietic cell transplant” [HCT], and “other”). Patient characteristics, type of exposure and varicella outcome, and safety data were assessed.Results: This analysis included 40 adults (primary [n = 6] or oncologic [n = 10] immunodeficiencies, history of SOT [n = 5] or HCT [n = 6], and other [n = 13]), and 263 children (primary [n = 13] or oncologic [n = 152] immunodeficiencies, history of SOT [n = 36] or HCT [n = 17], and other [n = 45]). Among adults and children, 48% vs 72% were exposed to varicella, 38% vs 16% were exposed to herpes zoster, and 15% vs 12% had an unspecified exposure. Overall incidence of varicella infection in adults after VARIZIG use was 6%; incidence of varicella infection in children after VARIZIG use was 7%. Similar rates were noted in each subgroup. Most cases of varicella were mild, with two children developing > 100 lesions and no cases of varicella-related pneumonia or encephalitis. Varicella-related hospitalizations occurred primarily in children with oncologic immunodeficiencies. One serious adverse event (serum sickness) was considered related to VARIZIG and occurred in a child with oncologic immunodeficiency. There were no varicella- or VARIZIG-related deaths.Conclusions: These data indicate that VARIZIG may reduce severity of varicella in immunocompromised children and adults.Trial registration: This study was retrospectively registered with the public clinical trial identificationNCT00338442athttps://www.clinicaltrials.govon 20 June 2006.

Infections following orthotopic liver transplant (OLT) result in significant morbidity and mortality, warranting careful consideration of risks associated with antibiotic overuse and benefits of infection prevention. In the absence of specific guidelines for antimicrobial prophylaxis in pediatric OLT, we developed a standardized approach to post‐operative (post‐op) antimicrobial therapy including 48 hours of antibiotics, no vancomycin for post‐op fever within the first 48 hours, and caspofungin only for certain situations. The goal was to reduce antimicrobial utilization and adverse outcomes associated with longer duration of and broader treatment while maintaining good outcomes. The impact of this standardization on antimicrobial utilization and clinical outcomes at the largest pediatric liver transplant center in the United States is described. All individuals receiving an OLT from 1/1/17‐9/30/17 (N = 38) and 3/14/18‐12/13/18 (N = 27) were included in the pre‐intervention (PreI) and post‐intervention (PostI) groups, respectively. The intervention resulted in a significant reduction in individuals receiving post‐op broad‐spectrum gram‐negative antibiotics for >48 hours (76% PreI vs 44% PostI OLT recipients,P = .01) and post‐op vancomycin use (50% PreI, vs 7.4% PostI,P < .001). There were no statistically significant differences between groups for post‐op fever, positive pre‐/post‐operative cultures, receipt of massive transfusion, or hospital length of stay. In conclusion, following the implementation of a standardized approach to post‐op prophylaxis, antimicrobial exposure was significantly reduced without affecting OLT recipient outcomes.