COVID-19 vaccination induces distinct T-cell responses in pediatric solid organ transplant recipients and immunocompetent children.

Immune responses to COVID-19 vaccination are attenuated in adult solid organ transplant recipients (SOTRs) and additional vaccine doses are recommended for this population. However, whether COVID-19 mRNA vaccine responses are limited in pediatric SOTRs (pSOTRs) compared to immunocompetent children is unknown. Due to SARS-CoV-2 evolution and mutations that evade neutralizing antibodies, T cells may provide important defense in SOTRs who mount poor humoral responses. Therefore, we assessed anti-SARS-CoV-2 IgG titers, surrogate neutralization, and spike (S)-specific T-cell responses to COVID-19 mRNA vaccines in pSOTRs and their healthy siblings (pHCs) before and after the bivalent vaccine dose. Despite immunosuppression, pSOTRs demonstrated humoral responses to both ancestral strain and Omicron subvariants following the primary ancestral strain monovalent mRNA COVID-19 series and multiple booster doses. These responses were not significantly different from those observed in pHCs and significantly higher six months after vaccination than responses in adult SOTRs two weeks post-vaccination. However, pSOTRs mounted limited S-specific CD8+ T-cell responses and qualitatively distinct CD4+ T-cell responses, primarily producing IL-2 and TNF with less IFN-γ production compared to pHCs. Bivalent vaccination enhanced humoral responses in some pSOTRs but did not shift the CD4+ T-cell responses toward increased IFN-γ production. Our findings indicate that S-specific CD4+ T cells in pSOTRs have distinct qualities with unknown protective capacity, yet vaccination produces cross-reactive antibodies not significantly different from responses in pHCs. Given altered T-cell responses, additional vaccine doses in pSOTRs to maintain high titer cross-reactive antibodies may be important in ensuring protection against SARS-CoV-2.

Anti-spike antibody durability after SARS-CoV-2 vaccination in adolescent solid organ transplant recipients.

BACKGROUND: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs. METHODS: Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3. RESULTS: All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine. CONCLUSIONS: The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron.

Omicron Infections in Vaccinated Pediatric Solid Organ Transplant Recipients.

SARS-CoV-2 infection during the Omicron period was frequent amongst a cohort of vaccinated pediatric solid organ transplant recipients (pSOTRs) despite robust anti-receptor-binding domain (anti-RBD) antibody response, suggesting poor neutralizing capacity against Omicron subvariants. Breakthrough infections among pSOTRs were overall limited in severity.

Comprehensive quality initiative leads to immediate postoperative extubation following liver transplant.

BACKGROUND: Immediate postoperative extubation (IPE) can reduce perioperative complications and length of stay (LOS), however it is performed variably after liver transplant across institutions and has historically excluded high-risk recipients from consideration. In late 2012, we planned and implemented a single academic institution structured quality improvement (QI) initiative to standardize perioperative care of liver transplant recipients without exceptions. We hypothesized that such an approach would lead to a sustained increase in IPE after primary (PAC) and delayed abdominal closure (DAC). METHODS: We retrospectively studied 591 patients from 2013 to 2018 who underwent liver transplant after initiative implementation. We evaluated trends in incidence of IPE versus delayed extubation (DE), and reintubation, LOS, and mortality. RESULTS: Overall, 476/591 (80.5%) recipients underwent PAC (278 IPE, 198 DE) and 115/591 (19.5%) experienced DAC (39 IPE, 76 DE). When comparing data from 2013 to data from 2018, the incidence of IPE increased from 9/67 (13.4%) to 78/90 (86.7%) after PAC and from 1/12 (8.3%) to 16/23 (69.6%) after DAC. For the same years, the incidence of IPE after PAC for recipients with MELD scores ≥30 increased from 0/19 (0%) to 12/17 (70.6%), for recipients who underwent simultaneous liver-kidney transplant increased from 1/8 (12.5%) to 4/5 (80.0%), and for recipients who received massive transfusion (>10 units of packed red blood cells) increased from 0/17 (0%) to 10/13 (76.9%). Reintubation for respiratory considerations <48 h after IPE occurred in 3/278 (1.1%) after PAC and 1/39 (2.6%) after DAC. IPE was associated with decreased intensive care unit (HR of discharge: 1.92; 95% CI: 1.58, 2.33; P < 0.001) and hospital LOS (HR of discharge: 1.45; 95% CI: 1.20, 1.76; P < 0.001) but demonstrated no association with mortality. CONCLUSION: A structured QI initiative led to sustained high rates of IPE and reduced LOS in all liver transplant recipients, including those classified as high risk.

Impact of Seasonal Coronavirus Antibodies on Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responses in Solid Organ Transplant Recipients.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination are reduced in solid organ transplant recipients (SOTRs). We report that increased levels of preexisting antibodies to seasonal coronaviruses are associated with decreased antibody response to SARS-CoV-2 vaccination in SOTRs, supporting that antigenic imprinting modulates vaccine responses in SOTRs.

Student curriculum review team, 8 years later: Where we stand and opportunities for growth.

BACKGROUND: The Student Curriculum Review Team (SCRT) was founded at the Johns Hopkins University School of Medicine (JHUSOM) in 2012 to refine pre-clinical courses. Since then, SCRT has provided a voice for student feedback - offering forums for discussion through 'Town Hall meetings' and confidential avenues for peer-to-peer comments. Here, we assess the perceived efficacy and utility of SCRT among the student body and faculty course directors. METHODS: A cross-sectional analysis was conducted in 2019 using an anonymous survey distributed to second- (MS2) and third-year (MS3) medical students as well as faculty course directors at JHUSOM. RESULTS: A total of 113 student surveys and 13 faculty surveys were returned. The majority of students (97%) endorsed SCRT as effective in enabling them to express their concerns. Most faculty (69%) reported SCRT's impact on their respective course as positive and found SCRT suggestions to be 'realistic and actionable.' Students (84%) and faculty (62%) alike considered SCRT to meet needs not met by other curricular organizations at JHUSOM. CONCLUSION: Students and faculty find that SCRT satisfies an unfilled position in the landscape of curricular feedback at JHUSOM. This study may be beneficial for other academic institutions considering ways to better engage students in curricular reform.

Blood utilization and clinical outcomes in pancreatic surgery before and after implementation of patient blood management.

BACKGROUND: Over the past decade, patient blood management (PBM) programs have been developed to reduce allogeneic blood utilization. This is particularly important in pancreatic surgery, which has historically been associated with high transfusion requirements and morbid event rates. This study investigated blood utilization and clinical outcomes in pancreatic surgery before, during, and after the implementation of PBM. STUDY DESIGN AND METHODS: A total of 3482 pancreatic surgery patients were assessed in a 10-year retrospective cohort study (2009-2019) at a single academic center. Baseline patient characteristics, transfusion practices, postoperative morbidity (infectious, thrombotic, ischemic, respiratory, and renal complications), mortality, and length of stay were compared between patients in the pre-PBM (2009-2013), early-PBM (2014-2016), and mature-PBM (2017-2019) time periods. Multivariable analysis assessed the odds for composite morbidity/mortality. RESULTS: Comparing the mature-PBM to pre-PBM cohorts, transfused units per 100 discharged patients decreased by 53% for erythrocytes (155 to 73; P < .0001), 81% for plasma (79 to 15; P < .038), and 75% for platelets (10 to 2.5; P < .005). Clinical outcomes improved as well, with composite morbid event rates decreasing by more than 50%, from 236 in 1438 patients (16.4%) to 85 in 1145 patients (7.4%) (P < .0001). Mortality and length of stay remained unchanged. Compared to the pre-PBM time period, early-PBM was associated with a risk-adjusted decrease in composite morbidity/mortality (OR 0.73; 95% CI 0.57-0.93; P = .010), while mature-PBM demonstrated a further incremental decrease (OR 0.44; 95% CI 0.33-0.57; P < .0001). CONCLUSIONS: The implementation of PBM was associated with substantially decreased blood utilization in pancreatic surgery, without negatively impacting clinical outcomes.

Comorbidities Associated with Granuloma Annulare: A Cross-Sectional, Case-Control Study.

Background: Granuloma annulare (GA) is a cutaneous granulomatous disorder of unknown etiology. There are conflicting data on the association between GA and multiple systemic conditions. As a result, we aimed to clarify the reported associations between GA and systemic conditions. Methods: A retrospective, cross-sectional, case-control study was performed in which the medical records of biopsy-confirmed GA patients ≥18 years of age, who presented to the Johns Hopkins Hospital System between 1 January 2009 and 1 June 2019, were reviewed. GA patients were compared to controls matched for age, race, and sex. Results: After adjusting for confounders, GA patients (n = 82) had higher odds of concurrent type II diabetes (odds ratio (OR) = 5.27; 95% confidence interval (CI), 1.73-16.07; p < 0.01), non-migraine headache (OR = 8.70; 95% CI, 1.61-46.88; p = 0.01), and a positive smoking history (OR = 1.93; 95% CI, 1.10-3.38; p = 0.02) compared to controls (n = 164). Among GA patients, women were more likely to have ophthalmic conditions (p = 0.04), and men were more likely to have cardiovascular disease (p < 0.01) and type II diabetes (p = 0.05). No differences in systemic condition associations were observed among GA subtypes. Conclusions: Our results support the reported association between GA and type II diabetes. Furthermore, our findings indicate that GA may be associated with cigarette smoking and non-migraine headache disorders.

Poor Cost Awareness Among Anesthesia Providers for Medications, Supplies, and Blood Products.

BACKGROUND: The objective of this study was to determine if anesthesia providers can accurately estimate the cost of commonly used medications, supplies, and blood products. METHODS: This study was conducted between April and June 2019 at an academic tertiary care hospital. Anesthesia providers (certified registered nurse anesthetists [CRNAs], residents, and fellows/attendings) were surveyed on their knowledge of the cost of commonly used therapies. Items were sorted into 12 categories: opioids, non-opioid analgesia, vasopressors, hypertension medications, antibiotics, neuromuscular blockers, reversals, anesthetics, supplies, kits, blood products, and blood-related products. Estimates were considered to be accurate if the median cost differed from the average wholesale price by < 25%, moderately inaccurate if between 25% and 50%, and severely inaccurate if by > 50%. RESULTS: A total of 107 surveys (CRNAs: 25, residents: 36, fellows/attendings: 46) were returned. The percentage of total items accurately estimated for cost was low (22% for all providers), and was not different between provider types (27% for CRNAs, 23% for residents, 20% for fellows/attendings; p = 0.69). The percentage of items with severe inaccuracies in cost estimation was high and was not different between provider types (56% for CRNAs, 60% for residents, 50% for fellows/attendings; p = 0.53). Rates of under- and overestimation varied widely, with greatest underestimation for vasopressors and blood-related products, and greatest overestimation for non-opioid analgesia and antibiotics. Low- and high-cost category items tended to be overestimated and underestimated, respectively (p < 0.0001). CONCLUSION: The majority of anesthesia providers have poor knowledge of cost. These findings suggest that cost awareness interventions may be necessary for promoting high-value health care.

Blood Utilization and Clinical Outcomes in Extracorporeal Membrane Oxygenation Patients.

BACKGROUND: Patients requiring extracorporeal membrane oxygenation (ECMO) support are critically ill and have substantial transfusion requirements, which convey both risks and benefits. A retrospective analysis was conducted to assess the association between blood component administration and adverse outcomes in adult, pediatric, and neonatal ECMO patients. METHODS: We evaluated 217 ECMO patients at a single center hospitalized between January 2009 and June 2016. Three cohorts (88 adult, 57 pediatric, and 72 neonatal patients) were included for assessment of patient characteristics, blood utilization, and clinical outcomes. Univariable and multivariable analyses were used to assess the association between transfusions and clinical outcomes (primary outcome: mortality and secondary outcomes: morbid events). The analysis included the main exposure of interest (total number of blood component units transfused) and potential confounding variables (age group cohort, case mix index, sex, ECMO mode and duration, and primary ECMO indication). RESULTS: After adjustment for confounders, with each additional blood component unit transfused, there was an estimated increase in odds for mortality by 1% (odds ratio [OR] = 1.01; 95% confidence interval [CI], 1.00-1.02; P = .013) and an increase in odds for thrombotic events by 1% (OR = 1.01; 95% CI, 1.00-1.02; P = .007). Mortality was higher in the adult (57 of 88; 64.8%) and pediatric (37 of 57; 64.9%) than in the neonatal cohort (19 of 72; 26.4%) (P < .0001). Median total blood components transfused per day followed a similar pattern for the adult (2.3 units; interquartile range [IQR] = 0.8-7.0), pediatric (2.9 units; IQR = 1.1-10), and neonatal (1.0 units; IQR = 0.7-1.6) cohorts (P < .0001). Over the entire hospitalization, the total median blood components transfused was highest in the neonatal (41 units; IQR = 24-94) and pediatric (41 units; IQR = 17-113) compared to the adult (30 units; IQR = 9-58) cohort (P = .007). There was no significant interaction between total units transfused over the hospital stay and age cohort for mortality (P = .35). CONCLUSIONS: Given the association between transfusion and adverse outcomes, effective blood management strategies may be beneficial in ECMO patients.

The impact of patient blood management on blood utilization and clinical outcomes in complex spine surgery.

BACKGROUND: Patient blood management (PBM) is especially applicable in major spine surgery, during which bleeding and transfusion are common. What remains unclear in this setting is the overall impact of bundled PBM measures on transfusion requirements and clinical outcomes. We compared these outcomes before and after implementing a PBM program. STUDY DESIGN AND METHODS: We conducted a retrospective review of 928 adult complex spine surgery patients performed by a single surgeon between January 2009 and June 2016. Although PBM measures were phased in over time, tranexamic acid (TXA) administration became standard protocol in July 2013, which defined our pre- and post-PBM periods. Transfusion rates for all blood components before and after PBM implementation were compared, as were morbid event rates and mortality. RESULTS: Baseline characteristics were similar before and after PBM. Before PBM, the mean number of units/patient decreased for red blood cells (RBCs; by 19.5%; p = 0.0057) and plasma (by 33%; p = 0.0008), but not for platelets (p = 0.15). After risk adjustment by multivariable analyses, the composite outcome of morbidity or mortality showed a nonsignificant trend toward improvement after PBM (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.39-1.01; p = 0.055), and the risk of thrombotic events was unchanged (OR, 1.12; 95% CI, 0.42-2.58; p = 0.80). CONCLUSION: In complex spine surgery, a multifaceted PBM program that includes TXA can be advantageous by reducing transfusion requirements without changing clinical outcomes.