Microbiological features of drowning-associated pneumonia: a systematic review and meta-analysis.

BACKGROUND: Drowning-associated pneumonia (DAP) is frequent in drowned patients, and possibly increases mortality. A better understanding of the microorganisms causing DAP could improve the adequacy of empirical antimicrobial therapy. We aimed to describe the pooled prevalence of DAP, the microorganisms involved, and the impact of DAP on drowned patients. METHODS: Systematic review and meta-analysis of studies published between 01/2000 and 07/2023 reporting on DAP occurrence and microorganisms involved. RESULTS: Of 309 unique articles screened, 6 were included, involving 688 patients. All were retrospective cohort studies, with a number of patients ranging from 37 to 270. Studies were conducted in Europe (France N = 3 and Netherland N = 1), United States of America (N = 1) and French West Indies (N = 1). Mortality ranged between 18 to 81%. The pooled prevalence of DAP was 39% (95%CI 29-48), similarly following freshwater (pooled prevalence 44%, 95%CI 36-52) or seawater drowning (pooled prevalence 42%, 95%CI 32-53). DAP did not significantly impact mortality (pooled odds ratio 1.43, 95%CI 0.56-3.67) but this estimation was based on two studies only. Respiratory samplings isolated 171 microorganisms, mostly Gram negative (98/171, 57%) and mainly Aeromonas sp. (20/171, 12%). Gram positive microorganisms represented 38/171 (22%) isolates, mainly Staphylococcus aureus (21/171, 12%). Water salinity levels had a limited impact on the distribution of microorganisms, except for Aeromonas sp. who were exclusively found following freshwater drowning (19/106, 18%) and never following seawater drowning (0%) (p = 0.001). No studies reported multidrug-resistant organisms but nearly 30% of the isolated microorganisms were resistant to amoxicillin-clavulanate, the drug that was the most commonly prescribed empirically for DAP. CONCLUSIONS: DAP are commonly caused by Gram-negative bacteria, especially Aeromonas sp. which is exclusively isolated following freshwater drowning. Empirical antimicrobial therapy should consider covering them, noting than amoxicillin-clavulanate may be inadequate in about one-third of the cases. The impact of DAP on patients' outcome is still unclear.

Total face mask with neurally adjusted ventilatory assist as a rescue therapy in infants with severe bronchiolitis.

Severe bronchiolitis patients are often supported with non-invasive ventilation (NIV). In case of NIV failure, we recently started to use non-invasive neurally adjusted ventilatory assist ventilation (NIV-NAVA) with a total face mask interface (TFM) and report now our experience with this modality of respiratory support. Retrospective study was made from October 2022 to May 2023 at the Geneva University Hospital Paediatric Intensive Care Unit. Inclusion criteria were children, aged from 0 to 6 months, with severe bronchiolitis with initial NIV failure and switch to NIV-NAVA-TFM. From 49 children with respiratory syncytial virus (RSV)-induced bronchiolitis requiring any form of respiratory support, 10 (median age 61 days (IQR 44-73) failing CPAP or NIV underwent rescue treatment with NIV-NAVA using a TFM. Patients were switched to TFM-NIV-NAVA 8 h (IQR 3-22) after admission for 24.5 h (IQR 13-60). After initiation of TFM-NIV-NAVA, oxygenation improved significantly as early as 1 h after initiation, whereas transcutaneous CO2 values remained stable. None of the patients needed to be intubated and there was no episode of TFM discontinuation due to interface discomfort or other unwanted side effects. Sedation was used in all patients with high proportion of intravenous dexmedetomidine. Median ventilatory assistance duration was 2.5 days (IQR 2-4) and median PICU stay was 4.5 (IQR 3-6).   Conclusion: In infants with severe RSV-induced bronchiolitis, respiratory support with TFM-NIV-NAVA seems to be feasible as a rescue therapy and might be considered in selected patients. What is Known: • Bronchiolitic patients with NIV support failure may require invasive mechanical ventilation. • Interface related complications, especially facial sores, can be a cause of NIV failure. What is New: • Total face mask with non-invasive neurally adjusted ventilatory assist (TFM-NIV-NAVA) seems feasible as a rescue therapy in deteriorating patients with CPAP or NIV failure. • TFM-NIV-NAVA can improve oxygenation rapidly in patients with aggravating hypoxemia and seems to be well tolerated.

Significance of colonization by antibiotic-resistant organisms prior to congenital heart disease surgery in children from low- to middle-income countries sent by non-governmental organizations to Switzerland.

PURPOSE: Children with congenital heart disease (CHD) from low- to middle-income countries (LMIC) are suspected to have a high prevalence of antibiotic-resistant microorganisms (ARMOs) carriage, but data are currently lacking. Carriage of ARMOs could impact the post-operative course in pediatric intensive care unit (PICU). The aim of the study was to assess the prevalence of ARMOs carriage in children with CHD from LMIC and its impact on post-operative outcomes. METHODS: This was a retrospective monocentric study from 01/2019 to 12/2022. Included patients were children (0-18 years) from a LMIC admitted after CHD surgery and with AMRO screening performed the week before. Infections and post-operative evolution were compared based on ARMOs carriage status. FINDINGS: Among 224 surgeries (median age 38.5 months (IQR 22-85.5)), ARMOs carriage was evidenced in 95 cases (42.4%). Main organisms isolated were Extended Spectrum Beta-Lactamase (ESBL) producing E. coli (75/224) 33.5%)) and ESBL-K. pneumoniae (30/224) 13.4%)). Median mechanical ventilation duration was 1 day (IQR 0-1), PICU stay 3 days (IQR 2-4) and hospital stay 6.5 days (IQR 5-10). A total of 17 infectious episodes occurred in 15 patients, mostly consisting in hospital-acquired pneumonia (HAP) (12/17). Only two infections were caused by a colonizing ARMO. Occurrence of infections and patients' outcome were similar between ARMO carriers and non-carriers. Higher use of carbapenems (6 (6.3%) vs 1 (0.8%), p = 0.04) and a trend to a higher use of vancomycin (14 (13.7%) vs 9 (6.9%), p = 0.04) in case of ARMOs carriage. Applying current guidelines, negative swab screening could have led to sparing most of empirical vancomycin therapy (11/12) for HAP based on current guidelines. CONCLUSION: Prevalence of AMROs carriage is high in children from LMIC and has a limited impact on patients' outcome. However, ARMOs carriage leads to higher consumption of antibiotics. Screening may help saving use of broad-spectrum antibiotic in non-carrier patients.

Extracorporeal Membrane Oxygenation After Liver Transplant in Children: A Review of the ELSO Registry.

There are minimal data describing use of extracorporeal membrane oxygenation (ECMO) in pediatric patient after a liver transplantation (LT). This study aimed at describing ECMO run in this specific situation using the data from Extracorporeal Life Support Organization (ELSO) Registry between January 1, 2010, to December 31, 2022. We described patients' characteristics at ECMO initiation, outcome and mortality risk factors. We identified 27 patients with a median age of 2.7 years (interquartile range (IQR) = 1.5-9.9). Main indication for ECMO support was respiratory (14/27 [52%]) followed by extracorporeal cardiopulmonary resuscitation (ECPR) (7/27 [26%]) and cardiac (6/27 [22%]). Overall in-hospital mortality was 63% (17/27). Mortality rate according to ECMO indications was 50% for both respiratory and cardiac failure and reached 100% for ECPR patients. Overall, nonsurvivors experienced significantly more complications under ECMO support (p = 0.007). Main on-ECMO complications were hemorrhagic (11/27 [41%]) and thrombotic (7/27 [26%]). No clinical or biologic factors was predictive of patients' outcome. Our results suggest that ECMO support is a viable option for cardiac and respiratory indications after pediatric LT. Occurrence of complications while on ECMO are associated with unfavorable outcomes. The extremely high mortality rate in ECPR patients merits further research.

Administering Nitric Oxide (NO) with High Flow Nasal Cannulas: A Simple Method.

Inhaled nitric oxide (iNO) is a pulmonary vasodilator that plays an important clinical ICU role. The administration of iNO is usually performed through an endotracheal tube, but spontaneously breathing patients might also benefit from iNO administration. The use of the non-invasive administration of iNO through high-flow nasal cannula (HFNC) allows for NO delivery in spontaneously breathing patients who still need supplemental oxygen and positive airway pressure. A simple method to administer NO through HFNC is described here using standard commercially available NO administration and HFNC.

Infective Endocarditis Due to Kingella kingae.

Infective endocarditis due to Kingella kingae is a rare but serious invasive infection that occurs mostly in children. Recent advances in nucleic acid amplification testing as well as in cardiac imaging have enabled more accurate diagnosis. A good understanding of the epidemiology and virulence factors remains crucial to guide the therapeutic approach. Here, we synthesize the current state of knowledge on epidemiological features, pathophysiological insights, complications, and therapy regarding Kingella kingae endocarditis in children and adults. Finally, throughout this comprehensive review, knowledge gaps and areas for future research are also identified.

Death by Neurologic Criteria in Children Undergoing Extracorporeal Cardiopulmonary Resuscitation: Retrospective Extracorporeal Life Support Organization Registry Study, 2017-2021.

OBJECTIVES: To determine factors associated with brain death in children treated with extracorporeal cardiopulmonary resuscitation (E-cardiopulmonary resuscitation). DESIGN: Retrospective database study. SETTINGS: Data reported to the Extracorporeal Life Support Organization (ELSO), 2017-2021. PATIENTS: Children supported with venoarterial extracorporeal membrane oxygenation (ECMO) for E-cardiopulmonary resuscitation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Data from the ELSO Registry included patient characteristics, blood gas values, support therapies, and complications. The primary outcome was brain death (i.e., death by neurologic criteria [DNC]). There were 2,209 children (≥ 29 d to < 18 yr of age) included. The reason for ECMO discontinuation was DNC in 138 patients (6%), and other criteria for death occurred in 886 patients (40%). Recovery occurred in 1,109 patients (50%), and the remaining 76 patients (4%) underwent transplantation. Fine and Gray proportional subdistribution hazards' regression analyses were used to examine the association between variables of interest and DNC. Age greater than 1 year ( p < 0.001), arterial blood carbon dioxide tension (Pa co2 ) greater than 82 mm Hg ( p = 0.022), baseline lactate greater than 15 mmol/L ( p = 0.034), and lactate 24 hours after cannulation greater than 3.8 mmol/L ( p < 0.001) were independently associated with greater hazard of subsequent DNC. In contrast, the presence of cardiac disease was associated with a lower hazard of subsequent DNC (subdistribution hazard ratio 0.57 [95% CI, 0.39-0.83] p = 0.004). CONCLUSIONS: In children undergoing E-cardiopulmonary resuscitation, older age, pre-event hypercarbia, higher before and during ECMO lactate levels are associated with DNC. Given the association of DNC with hypercarbia following cardiac arrest, the role of Pa co2 management in E-cardiopulmonary resuscitation warrants further studies.

Use of CO2-Derived Variables in Cardiac Intensive Care Unit: Pathophysiology and Clinical Implications.

Shock is a life-threatening condition, and its timely recognition is essential for adequate management. Pediatric patients with congenital heart disease admitted to a cardiac intensive care unit (CICU) after surgical corrections are particularly at risk of low cardiac output syndrome (LCOS) and shock. Blood lactate levels and venous oxygen saturation (ScVO2) are usually used as shock biomarkers to monitor the efficacy of resuscitation efforts, but they are plagued by some limitations. Carbon dioxide (CO2)-derived parameters, namely veno-arterial CO2 difference (ΔCCO2) and the VCO2/VO2 ratio, may represent a potentially valuable addition as sensitive biomarkers to assess tissue perfusion and cellular oxygenation and may represent a valuable addition in shock monitoring. These variables have been mostly studied in the adult population, with a strong association between ΔCCO2 or VCO2/VO2 ratio and mortality. In children, particularly in CICU, few studies looked at these parameters, while they reported promising results on the use of CO2-derived indices for patients' management after cardiac surgeries. This review focuses on the physiological and pathophysiological determinants of ΔCCO2 and VCO2/VO2 ratio while summarizing the actual state of knowledge on the use of CO2-derived indices as hemodynamical markers in CICU.

Long-term Outcome of Asymptomatic Patients With Graft Fibrosis in Protocol Biopsies After Pediatric Liver Transplantation.

BACKGROUND: The histological prevalence of allograft fibrosis in asymptomatic children after liver transplantation (LT) is well documented. However, long-term graft and patient survival remain unclear. This retrospective multicenter study aims to determine the prevalence of allograft fibrosis and analyze the long-term outcome for patients transplanted in childhood. METHODS: We reviewed clinical data of children who had undergone 10-y protocol liver biopsies. We excluded patients with autoimmune hepatitis, primary sclerosing cholangitis, hepatitis B or C, and retransplantation. In total, 494 patients transplanted in childhood across 12 international transplant centers were included. We evaluated the development of fibrosis by comparing the results with biopsies obtained 5 and 15 y post-LT. Histological findings were correlated with graft and patient survival up to 20 y post-LT. RESULTS: In the 10-y biopsies, periportal or pericentral fibrosis was observed in 253 patients (51%), 87 (18%) had bridging fibrosis, 30 (6%) had cirrhosis, and 124 (25%) had no fibrosis. The prevalence and stage of graft fibrosis significantly progressed from 5 to 10 y. At 10 y, the severity of fibrosis correlated significantly with inflammation. Patients with graft cirrhosis in the 10-y biopsy were more likely to die or require retransplantation subsequently ( P = 0.027). CONCLUSIONS: At 10 y post-LT, most patients transplanted in childhood developed fibrosis, based on the protocol liver biopsies. Although mild-to-moderate graft fibrosis did not largely affect patient or graft survival up to 20 y post-LT, this progressive fibrosis finding has substantial implications for developing cirrhosis and portal hypertension in adult care.

Blood Purification with oXiris© in Critically Ill Children with Vasoplegic Shock.

INTRODUCTION: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. As such, circulating cytokines and danger- and pathogen-associated molecular patterns (such as endotoxins) are recognized as central in the pathogenesis of sepsis and organ dysfunction. Removing these compounds by extracorporeal blood filtration, commonly considered blood purification, may improve the septic patients' condition. This study aimed to assess the vaso-inotropic support evolution over time in pediatric patients with vasoplegic shock treated with oXiris©. METHODS: All patients aged below 18 years admitted at the Paris Saclay University Quaternary Pediatric Intensive Care Unit with vasoplegic shock and acute kidney injury and treated with oXiris© between October 2017 and January 2020 were included. The vaso-inotropic score and the 28-day mortality were assessed. Improvement under treatment was defined as a 50% decrease in the vaso-inotropic score following 24 h of oXiris© therapy. RESULTS: Eleven pediatric patients aged 2-15 years and weighing 11-60 kg were admitted with vasoplegic shock and acute kidney injury. They received thirteen sessions of oXiris© therapy for septic shock (N = 7) and liver failure (N = 6). Eight patients did not improve their condition during the session, and five ultimately died (37.5% survival). Five patients improved, decreasing their inotropic support by >50% in 24 h. Among them, four survived (80%). CONCLUSION: Hemofiltration and extracorporeal blood purification with oXiris© can be used in pediatric patients with vasoplegic shock with rapid improvement in hemodynamics in selected patients.

First nosocomial infections in children supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO).

BACKGROUND: Veno-arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a standard procedure for patient with refractory shock in Pediatric Intensive Care Unit (PICU). There is a paucity of data on the time relationship between VA-ECMO support, nosocomial infection occurrence, and PICU length of stay (LOS). The aim of this study was to determine the characteristics and impact of ECMO-related infections. METHODS: This is a retrospective study from 01/2008 to 12/2014, enrolling children with a VA-ECMO support for > 6 h. We recorded the first PICU infection during the VA-ECMO run, defined as a positive microbiological sample with clinical signs of infection or clinical signs of severe infection without positive sample. RESULTS: During the study period, 41 patients (25/41 male) were included, with a median age of 41.2 months (IQR 12.9-89.9) and a 53% mortality rate. Median time on VA-ECMO was 4.2 d (IQR 2-7.1), median PICU LOS was 14.7 d (IQR 4,7-26,9). Overall, 34% patients developed an infection, with an incidence of 60/1000 VA-ECMO days. Median time to first infection was 4 d (IQR 3-5), with Pseudomonas spp. being the most commonly detected microorganism (42%). Infected sites were ventilator-associated pneumonia (9/14), sternotomy infection (2/14), bloodstream (2/14) and urinary tract infections (1/14). Longer VA-ECMO support (> 5 d) (OR 5.9 (CI 95% 1.4-24.6; p = 0.01) and longer PICU stay (> 14 d) (OR 12 (95% CI 2.2-65.5; p = 0.004) were associated with infection. CONCLUSION: In this single-center study, we underlined the high proportion and early occurrence of infections in patient on VA-ECMO, mostly in the first week. As infection was an early event, it may prolong the duration of VA-ECMO support and PICU LOS. Further research is needed to better understand the impact of infections on VA-ECMO and develop prevention strategies.

Multi-organ failure caused by lasagnas: A case report of Bacillus cereus food poisoning.

We report a Bacillus cereus, cereulide producing strain, food poisoning of two sisters. After eating a few bites of pasta cooked 3 days earlier, a 13-year-old girl developed mild symptoms. However, her 11-year-old sister suffered, 40 h after ingestion of the entire platter, a multi-organ failure including acute liver failure, rhabdomyolysis, disseminated intravascular coagulation, and acute kidney injury (AKI). She received supportive care in pediatric intensive care using mechanical ventilation, hemofiltration, and high-doses vasopressors. She was specifically treated for toxin-mediated disease using blood purification and further digestive decontamination. This report highlights the potential severity of B. cereus food poisoning but also a successful dual treatment including toxin removal and antimicrobial treatment to prevent toxin production.

Parents' Views with Music Therapy in the Pediatric Intensive Care Unit: A Retrospective Cohort Study.

PURPOSE: Music therapy intervention (MT) could be used as an adjunctive therapy in PICU for anxiety and pain management. The aim of the study was to examine the perception of MT by children's parents in a PICU of a tertiary care teaching hospital. METHODS: This is a retrospective cohort study summarizing the results of an institutional quality improvement initiative. Questionnaires were distributed to parents whose children were exposed to MT. RESULTS: From April 2019 to July 2021, 263 patients received a total of 603 h of MT. Twenty-five questionnaires were distributed to parents over a 4-month period (February-June 2021). A total of 19 (76%) parents completed the questionnaire. The majority of parents thought that MT helped their child to communicate (89%), feel less isolated (100%) and cope with stress during hospitalization (100%). The majority of parents also thought that MT contributed to physical recovery (90%) and alleviated feelings of anxiety (90%). Parents also believed that MT should be offered as an out-patient service. CONCLUSIONS: Our study agrees with other studies on the positive potentials of MT in PICU. Music therapy intervention could be used to promote children's and parents' psychological well-being. Further studies are warranted to evaluate the impact of MT on long-term post-ICU outcomes.

Use of Carboxyhemoglobin as an Early Sign of Oxygenator Dysfunction in Patients Supported by Extracorporeal Membrane Oxygenation.

Introduction: Plasma free hemoglobin is the gold standard for monitoring hemolysis in extracorporeal membrane oxygenation (ECMO) but its routine use has some limitations. Carboxyhemoglobin (HbCO) is also a marker of intravascular hemolysis. We aimed to investigate HbCO as a marker of both hemolysis and oxygenator dysfunction in patients supported by ECMO. Methods: Retrospective analysis of patients on ECMO in an adult ICU in a tertiary hospital. HbCO was recorded every 6 h in the 48 h before and after oxygenator change in adult patients on ECMO support with an oxygenator dysfunction and replacement. Results: The investigation of 27 oxygenators replacements in 19 patients demonstrated that HbCO values progressively increased over time and then significantly decreased after oxygenator change. Median oxygenator lifespan was 14 days [interquartile range (IQR) 8-21] and there was no correlation between HbCO and oxygenator lifespan [Spearman coefficient 0.23 (p = 0.23)]. HbCO values at oxygenator change [HbCO median 2.7 (IQR 2.5-3.5)] were significantly higher than the HbCO values 1 week before [HbCO median 2.07 (IQR 1.86-2.8)] (p value < 0.001). Conclusion: Our data highlight the potential role of HbCO as a novel marker for ECMO oxygenator dysfunction.

Transcranial Doppler Ultrasonography in Children With Acute Liver Failure and Severe Hepatic Encephalopathy.

OBJECTIVES: To report our single-center use of transcranial Doppler (TCD) for noninvasive neuromonitoring in pediatric patients with acute liver failure (ALF). DESIGN: Retrospective cohort from January 2016 to June 2019. SETTING: PICU in Bicêtre Hospital, Assistance Publique- Hôpitaux de Paris (AP-HP), a national referral center for pediatric liver transplantation. PATIENTS: Pediatric patients with severe ALF (prothrombin time < 30% and Hepatic Encephalopathy score ≥ 3), on continuous venovenous high-flow hemofiltration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ten children were identified, six were transplanted (1/6 died) and four were not (3/4 died). TCD was performed several times per patient and the evolution of cerebral perfusion parameters was followed. Of interest, zero of six patients who survived lost end-diastolic velocity (EDV), whereas four of four patients who died did (difference, 100%; 95% CI, 37-100%; χ 2 , 9; degrees of freedom, 1; p = 0.0027). We failed to identify an association between pulsatility index (PI) or EDV, and severity of hepatic encephalopathy. CONCLUSIONS: TCD was a noninvasive and bedside available tool to detect and screen for presence of abnormal cerebral flow in children with ALF, according to age-related reference values. TCD detected reduced EDV and elevated PI in children with ALF awaiting transplant who died compared with those who survived.

Pathophysiology of COVID-19: Everywhere You Look You Will See ACE2!

Angiotensin converting enzyme 2 (ACE2) seems to be a central actor in the pathophysiology of SARS-Cov-2 infection. First, it acts as the receptor for the virus and permits its attachment to cells expressing ACE2. Second, the relative deficiency of ACE2 during infection could be linked to several clinical features encountered during the disease, like ARDS and coagulation abnormalities. This study explores the strong link between ACE2 and the majority of risk factors for the severe evolution of COVID-19. It seems that all these risks factors are linked to an increased level of ACE2 and/or imbalance in ACE/ACE2.

Vitamin D Insufficiency Prior to Paediatric Liver Transplantation Is Associated with Early T-Cell Mediated Rejection.

Objectives: T-cell mediated rejection (TCMR) can compromise long-term liver allograft survival. The immunomodulatory properties of vitamin D are increasingly recognized. We investigated whether perturbations in vitamin D metabolism prior to LT may predispose to TCMR in a representative cohort of paediatric LT recipients. Methods: In this retrospective single-center study of children who underwent liver transplantation between 2005 and 2017, we collected serum 25(OH) vitamin D levels and other parameters related to vitamin D metabolism. Post-transplant variables were collected from medical records during the first year following LT. Results: Eighty-two patients were included. Twenty-six (32%) developed TCMR, 52 (65%) presented at least one event of 25(OH) D insufficiency during the year before the transplant, while 23 (32%) had at least one documented elevated plasma parathyroid hormone level. Forty-six patients benefited from nutritional support (56%). The development of TCMR was associated with vitamin D insufficiency pre-LT (p = 0.01). No significant correlations were identified between PTH levels and incidence of TCMR. The association was stronger in patients transplanted for cholestatic diseases (p = 0.004). Conclusions: Vitamin D insufficiency before a liver transplant may be associated with TCMR during the first year post-LT. These findings warrant further investigation.

Peripheral Donor-specific Antibodies Are Associated With Histology and Cellular Subtypes in Protocol Liver Biopsies of Pediatric Recipients.

BACKGROUND: The cellular infiltrate in protocol liver biopsies (PB) following pediatric liver transplantation remains mostly uncharacterized, yet there is increasing concern about the role of inflammation and fibrosis in long-term liver allografts. We aimed to define cell types in PB and to analyze their relationship with donor-specific antibodies (DSA) and histological phenotype. METHODS: PB were performed at least 1 year after transplantation. We identified 4 phenotypes: normal, fibrosis, inflammation, inflammation with fibrosis. Cell types were counted after immunostaining for CD3, CD4, CD8, CD68, CD20, MUM1, and FoxP3. RESULTS: Forty-four patients underwent 1 PB between 2000 and 2015. Eleven percent (5/44) of PB displayed normal histology, 13.6% (6/44) fibrosis, 34.1% (15/44) inflammation, and 40.9% (18/44) inflammation and fibrosis. The main cell types in the portal tracts and lobules were CD3+ and CD68+ cells. Frequency of de novo DSA was 63% (27/44). The presence of CD8+ cells in the lobules was associated with fibrosis. Inflammation and fibrosis in PB were associated with the presence of circulating de novo DSA, number of de novo DSA, and C1q binding activity when compared to other phenotypes. CONCLUSIONS: T cells (CD3+) and macrophages (CD68+) were the most prevalent cell-types in PB. In the presence of inflammation, portal tracts were enriched in CD3+, CD20+ but displayed fewer CD68+. This coincided with the presence and number of de novo DSA. How these cellular and humoral actors interact is unclear, but peripheral DSA may be a marker of immune cellular activity in the seemingly quiescent allograft.