Introduction: The outcomes of patients who fail their kidney transplant and return to dialysis (RTD) has not been investigated in a nationally representative sample. We hypothesized that variations in management of transplant chronic kidney disease stage 5 leading to kidney allograft failure (KAF) and RTD, such as access, nutrition, timing of dialysis, and anemia management predict long-term survival. Methods: We used an incident cohort of patients from the United States Renal Data System who initiated hemodialysis between January 1, 2003 and December 31, 2008, after KAF. We used Cox regression analysis for statistical associations, with mortality as the primary outcome. Results: We identified 5,077 RTD patients and followed them for a mean of 30.9 ± 22.6 months. Adjusting for all possible confounders at the time of RTD, the adjusted hazards ratio (AHR) for death was increased with lack of arteriovenous fistula at initiation of dialysis (AHR 1.22, 95% CI 1.02-1.46, p = 0.03), albumin <3.5 g/dL (AHR 1.33, 95% CI 1.18-1.49, p = 0.0001), and being underweight (AHR 1.30, 95% CI 1.07-1.58, p = 0.006). Hemoglobin <10 g/dL (AHR 0.96, 95% CI 0.86-1.06, p = 0.46), type of insurance, and zip code-based median household income were not associated with higher mortality. Glomerular filtration rate <10 mL/min/1.73 m² at time of dialysis initiation (AHR 0.83, 95% CI 0.75-0.93, p = 0.001) was associated with reduction in mortality. Conclusions: Excess mortality risk observed in patients starting dialysis after KAF is multifactorial, including nutritional issues and vascular access. Adequate preparation of patients with failing kidney transplants prior to resuming dialysis may improve outcomes.

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Introduction: Operative reconstruction is the preferred method of treatment for ruptured Achilles tendons in most patients. Several surgical approaches have been described. Sural nerve injury has been reported with each method. We believe that a lateral paramedian incision that allows direct visualisation and isolation of the sural nerve will reduce the frequency of nerve injury.Methods: A retrospective case control study in which we compared 34 patients from the open posterolateral paramedian approach with 33 patients in the standard open posteromedial paramedian incision. All patients in the posterolateral incision group were treated by the senior author using a 2 ethibond Krakow suture and wore a below knee plaster cast for 6 weeks followed by a heel raise for 4 weeks. In the second group, a 1 PDS modified Kessler core suture was used and patients were treated in cast for 8 weeks. All patients were recalled and 35 patients returned and clinically assessed. Calf circumference, Tendon width, AOFAS and Hannover Achilles Tendon Scores were completed in each case.Results: There were no significant wound complications.2 patients had re-ruptures in posteromedial group. Two patients in the posterolateral incision group had transient parasthesiae in the foot post-operatively. Both resolved within two weeks. The mean AOFAS scores in the posterolateral group was 89 compared with 85 in the posteromedial group (p = 0.76) while Hannover Achilles Tendon Scores (posteromedial 79/100, posterolateral 84/100, p = 0.45).Discussion: In our study both groups of patients had favourable outcomes, regardless of the surgical approach used. We did not identify a reduced incidence of sural nerve injury in the posterolateral incision group. The 2 cases of transient parasthesiae may have been due to traction on the sural nerve intra-operatively. We believe that a posterolateral incision is a safe and technically easy surgical approach in the reconstruction of Achilles tendon ruptures.

1904 Introduction: In Utero Hematopoietic Cell Transplantation (IUHCT) is a potential treatment for congenital hematologic disorders. The rationale is to utilize normal events during hematopoietic and immunologic development to facilitate hematopoietic engraftment. While the risk of graft versus host disease (GVHD) after IUHCT would be anticipated to be high, based on Medawar's tenets, surprisingly little GVHD has been observed after experimental IUHCT and IUHCT induced GVHD has not been previously characterized. To better understand the potential risk of IUHCT induced GVHD prior to clinical application, we attempted to intentionally induce GVHD pathophysiology in the allogeneic murine model of IUHCT. Methods: Bone marrow (BM) cells (10×106) from C57/BL6 (B6, H2kb, GFP−) mice were co-injected with increasing doses of splenocytes from B6-GFP (H2kb, GFP+) mice intravenously into Balb/c (H2kd) fetuses at embryonic day 14 (E14). Control groups included: 1) 10×106 B6 BM cells alone; 2) same doses of B6-GFP splenocytes alone; and 3) IUHCT of congenic donor cell populations into B6 recipients. Surviving pups were assessed using a clinical GVHD scale and separate cohorts were harvested at pre- and post-natal time-points for analysis by fluorescence stereoscopic microscopy (FSM), flow cytometry for assessment of donor and host cell populations in hematopoietic tissues, and histologic assessment of target tissues for GVHD. Results: Prenatal Analysis - In the allogenic groups that received 10×106 BM cells plus increasing doses of splenocytes (0.1×106 to 10×106 splenocytes/fetus) a consistent distribution of GFP positive cells could be seen by whole body FSM in lymphohematopoietic sites (spleen, lymph nodes, thymus and fetal liver) at E16 that did not differ significantly from congenic controls. By E19 – E20 however, marked proliferation of the cells occurred with clear infiltration of GVHD target organs (skin, lungs, liver, intestine). This expansion was proportionate to the dose of splenocytes and was not seen in congenic or BM only controls. Increased mortality was not observed until doses greater than 5 × 106 splenocytes were given (approx. 5 × 1011 splenocytes/kg est. fetal wt.) with perinatal death likely attributable to respiratory insufficiency. Postnatal Analysis - In the allogeneic groups there was minimal clinical evidence of GVHD up to and inclusive of the 5×106 splenocyte dose. A few pups showed poor growth relative to the normal growth curve and mild fur ruffling, but these resolved by P15, and there was no further clinical evidence of GVHD and no postnatal deaths up to P60. In harvested tissues many GFP+ cells persisted in GVHD target organs, however, no GVHD histopathology was observed at any time. Flow cytometric analysis confirmed a proliferation of donor splenocytes that peaked around P5-P10. Lymphocyte subset analysis revealed an expansion of predominantly CD8+ T-cells. Alkaline phosphatase in the host liver, as a marker of GVHD was increased during the same time course and returned to normal by P15. An increase of host and donor BM derived CD4+ cells was also observed that peaked around P15-17. Further analysis confirmed an increase in both T-regulatory cells and activated CD4+ T-cells compared to normal or BM only controls. The most remarkable observation was a dramatic graft versus hematopoietic (GVH) effect with an increase in donor BM derived chimerism at P60 to > 80% with no clinical GVHD. These findings were seen only in the allogenic group that received both splenocytes and bone marrow cells, not in the other groups. In the group that received only bone marrow cells, the chimerism remained at low levels (Figure 1). Conclusion: Our data demonstrates that the fetus is in fact resistant to GVHD relative to myeloablated postnatal BMT recipients. While there is an aggressive alloimmune activation and expansion of donor T-cells, clinical manifestations are mild and are reversed by what appears to be a T-regulatory cell expansion. In our model, the alloimmune activation phase is accompanied by a potent GVH response providing a competitive advantage for donor cells and resulting in marked enhancement of donor cell engraftment without clinical evidence of GVHD. Further work in this model is directed toward defining regulatory and effector mechanisms involved in controlling GVHD and the GVH effect. Disclosures: No relevant conflicts of interest to declare.

Posttraumatic stress among pediatric critical care physicians in the United States in association with coronavirus disease 2019 patient care experiences. Our objective was to assess the prevalence of posttraumatic stress (PTS) and its association with COVID-19 patient care experiences among pediatric critical care physicians. Our study was a cross-sectional study of pediatric critical care physicians in the United States. We measured PTS which included posttraumatic stress disorder (PTSD) and subthreshold posttraumatic stress disorder (SubPTSD) using validated PTSD Checklist- 5 survey tool. Association of PTS with COVID-19 patient care experiences was analyzed using regression analysis. Prevalence of PTS was noted in 120 among 294 pediatric critical care physicians (41%; 95% CI, 35-47%). The predominant symptoms were that of hyperarousal and feelings of negative cognition and mood. Among our physicians with PTS, 19% had PTSD and 81% had SubPTSD. Demographic and practice characteristics were not significant for increased PTS on regression analysis. Posttraumatic stress was significantly associated with physicians testing positive or taking time off for COVID-19 illness, self-isolation, fear of infecting their loved ones, families scared of being infected, feeling helpless, patients expressing fears of dying, having pre-existing depression, anxiety, or insomnia, working beyond comfort level of training and having thoughts of quitting (p < 0.05). Thoughts of quitting was associated with the highest significant increase in PTS scores (coefficient:11.643; 95% CI:8.551,14.735; P < 0.01) followed by feeling of helplessness (coefficient:11.055; 95% CI: 8.484,13.624; P < 0.01) and need for additional medications for depression, anxiety and insomnia (coefficient: 10.980; 95% CI: 4.970, 16.990; P < 0.01). Posttraumatic stress is high in pediatric critical care physicians and is associated with various COVID-19 patient care experiences. Thoughts of quitting was associated with highest increase in posttraumatic stress score which could have major implications for the workforce in the future. Subthreshold posttraumatic stress disorder should be recognized, and mental health issues of pediatric critical care physicians addressed.