A Single Centre Experience of Post Renal Transplant Infections in a Tertiary Care Centre in Eastern India

Introduction: In developing countries, Post renal-transplant infections is the leading cause of mortality, morbidity and decreased allograft survival. Our aims and objectives was to determine the incidence and prevalence patterns of clinically or microbiologically confirmed infection in the post renal transplant patients of our population and profiling of infections in relation to time period from the Transplant and the induction agent, also to develop strategies to counter risk of post transplant infection. Method(s): This was a retrospective observational study. Time period: January 2020- April 2022. Post renal transplant recipients presenting with infections (with informed consent) was enrolled in this study. Recurrent episodes of infection by different organisms in a same patient treated as a separate event. Data was tabulated using MS excel and all results projected in bar graphs, pie charts, histograms. Differences of quantitative parameters between groups were assessed using the t test(for data that were normally distributed) or nonparametric test (for data that were not normally distributed). Differences of qualitative results were compared using chi2 test. Kaplan-meier was used for survival analysis. P < 0.05 was considered significant. Result(s): 213 incidents of post renal transplant infections were documented in 148 patients between the study period. Of the 85 patients who underwent renal transplant(57 living donor and 28 cadaveric) in this time period 33(38.8%) patients presented with 42 incidents of infections. Majority (74.3%) : Males. Mean age: 36.3+/-5.6 years. Most common cause of native kidney disease was chronic glomerulonephritis(30%). 121 (81.7%) had living donor transplant and 27(8.3%) patients had cadaveric transplant. Induction agent was basiliximab in 97 patients (65.5%) had 133 infections (62.4%) and ATG was used in 51 patients (34.5%) had 80(37.6%) infections. In recent transplant (last 2 yrs) cases-In Basiliximab group: infection rate 4.1 in 100 patient months and in ATG group infection rate was 5.7 in 100 patient months. (p=0.28). 37.5%cases had infections with graft dysfunction most commonly AKI. Immediate post transplant infections (<1 month) were 34 (15.9%), most commonly UTI (44.11%) followed by pneumonia (15.9%). 48(%) infections occurred between 1-6 months, most commonly pneumonia(27.08%) followed by UTI(22.9%) and superficial fungal infection. Pulmonary tuberculosis was in 14 (6.6%) cases. 3 cases had disseminated TB. Infectious diarrhea was in 18(8.4%) cases, most common organism isolated was EAEC and EPEC. CMV colitis found in 3 cases. 27 (18.2%) patients had NODAT/PTDM. ParvoB19 was in 11(5.16%), CMV in 5 and BKVN in 3 cases. 41(19.2%) cases had severe sepsis requiring intensive care support. New baseline s.cr was achieved in 29.1% cases. Infection related death was 24(16.2%). COVID 19 infection was in 41 cases, 31.7% developed graft dysfunction and 18 (43.9%) required hospital admission due to moderate or severe disease. 2 patients had mucormycosis, one of them died after admission. [Formula presented] Conclusion(s): Profiling of infection in our centre is essential to formulate future strategies for infection control especially as the DDKT & ABOi KT is on the rise. Proper survillence, screening protocol, vaccination and patient education are essential to reduce the burden of post transplant infection and for better graft and patient survival. No conflict of interestCopyright © 2023

Management of Transplant Graft and Role of Immunosuppression in the Outcome of Covid-19 Infection in Solid Organ Transplant Recipients

Background. COVID-19 disease became a global health care crisis and was declared pandemic by WHO in March 2020. Little is known how the immunosuppressive medications impact the mortality rate in Solid Organ Transplant (SOT) recipients. There is also minimal data regarding the incidence of transplanted graft failure or rejection that could be attributed to the COVID-19 infection itself or its complications and management. Our study aims to investigate the management of COVID-19 infection, outcome of the infection, transplant failure and rejection rates in SOT recipients. Methods. We conducted a retrospective cohort study of all consecutive SOT recipients who were admitted to our transplant center from March 2020 to April 2021 with COVID-19 infection. Data was collected from the electronic medical records after receiving Institutional Review Board approval. Results. A total of 135 patients met the inclusion criteria. After the diagnosis of COVID -19 infection, 31% recipients had decrease in the dose of immunosuppressive medications (change group) and 69% had no changes in the dose (no change group). Out of the 73 Kidney Transplant recipients 33% were in the change group compared to 14% of liver, 25% of heart and 27% of lung transplant recipients. Of the total 42 recipients in the change group, 28.6% required Intensive Care Unit (ICU) level care significantly higher compared to 7.5% in the no change group (p-value < 0.005). Mechanical ventilation was required in 14.3% of the patients in the change group and 6.5% in the no change group (p-value < 0.5). Out of the total, 85.7% patients in the change group survived compared to 94.6% in the no change group (p-value < 0.1). Overall, the transplant rejection rate was higher in the change group compared to the no change group (p-value < 0.5). Conclusion. Our study showed a significantly higher ICU admission rate and mortality in SOT recipients who had their immune suppression reduced at the time of COVID-19 diagnosis. The same group also had a higher risk of rejection of transplanted graft. More studies with larger sample size needs to be done to further understand the management of immunosuppressive drugs in the SOT recipients with COIVD-19 infection.

Plasmapheresis and Rituximab for Prevention of Focal Segmental Glomerulosclerosis Recurrence Post-Kidney Transplantation

Purpose: Primary focal segmental glomerulosclerosis (FSGS) recurs after kidney transplantation (KT) in 30-50% of recipients with a median time of 1.5 months post- KT. Recurrence is associated with early graft loss in 60% of cases. The aim of this study is to assess the efficacy of pre-emptive therapeutic plasma exchange (TPE) and rituximab for the prevention of FSGS recurrence post-KT. Method(s): This single-center, retrospective study included patients receiving KT for primary FSGS between May 2016 and August 2021. Living-donor KT recipients received three sessions of TPE prior to scheduled transplant. Recipients of both living and deceased donor KT received 3 postoperative sessions of TPE followed by one dose of 375 mg/m2 rituximab with or without intravenous immune globulin (IVIG) 0.5 g/kg. Recipients underwent protocol biopsy at one month to screen for FSGS recurrence. The primary endpoint was a composite for disease recurrence including proteinuria (>=1 g/day) or/and biopsy-proven FSGS within one month. Result(s): 54 patients received KT for FSGS during the study period using the TPE/ rituximab protocol. 5 patients (9%) experienced FSGS recurrence within one month of transplant. A total of 10 patients (19%) were found to have disease recurrence within a year, with median (IQR) time to recurrence of 37 days (27-66). White race and history of hypertension were independent risk factors for recurrence, whereas African American race and diabetes were associated with a reduced risk of recurrence. 31 patients (57%) also received IVIG prior to discharge due to concerns for hypogammaglobulinemia. There were 18 documented infections in 13 patients (24%) within 3 months of transplant. Patients who received IVIG had significantly fewer cases of infection (3 cases: 1 viral and 2 COVID-19) compared to patients who did not receive IVIG (15 cases: 4 bacterial, 9 viral, 1 fungal, and 1 COVID-19), p<0.001. At one year, 9 patients (19%) had biopsy-proven rejection (5 acute cellular rejection, 1 antibody-mediated rejection, and 3 mixed rejection). There were no instances of graft loss or mortality observed at one year. Conclusion(s): The utilization of plasma exchange and rituximab may prevent early disease recurrence of FSGS without significant rates of infection, graft loss, or mortality.

Comparison of Outcomes and Management of COVID Infection Among Kidney Transplant Recipients Between Pre-Vaccination Rollout Era and Post-Vaccination Rollout Era

Purpose: The COVID pandemic has posed a significant challenge among kidney transplant recipients (KTR) due to their immunocompromised states. The effects of COVID vaccination on KTRs are uncertain. We sought to better understand the clinical course, management, and outcomes of KTRs who developed COVID infection during the pre-and post-COVID vaccine rollout periods. We also compared whether there was a difference in patient outcomes or management of COVID infection between the two groups. Method(s): This was a single-center study of KTRs who were infected with COVID. Baseline demographics, clinical parameters, COVID vaccination status, management, and outcomes were obtained by manual chart ion of the electronic medical records. Result(s): We studied a total of 134 KTRs in the pre-vaccination era and 83 KTRs after vaccination rollout who had COVID infections. The mean age of the patients was 54 years in both groups, and there was a greater proportion of African American KTRs in the pre-vaccination rollout era (70% vs. 53%, P=.02). No statistically significant differences were found among sex, BMI, or induction agents. In the pre-vaccination era, KTRs were more likely to present with fever (71% vs. 51%, P<.001). No statistically significant differences were observed in the onset of COVID infection after transplant, ICU admission, the requirement of mechanical ventilation therapy, incidence of AKI (acute kidney injury), requirement of renal replacement therapy (RRT), or incidence of acute rejection. For COVID infection management, KTRs in the post-vaccination rollout era were more likely to be treated with dexamethasone (47% vs. 32%, P=.035) . No statistically significant difference was found in the proportion of patients who required reduction or discontinuation of immunosuppressive agents. In the pre-vaccination era, KTRs were more likely to recover from acute kidney injury (57% vs, 25%, P=.01). No statistically significant difference was found in mortality between groups, but the risk of death was almost twice a high in the post-vaccination rollout era (21% vs. 12%). Conclusion(s): In this single-center case-control study, COVID vaccination rollout did not seem to have an appreciable impact on the incidence of hospitalization, ICU admission, AKI, RRT requirement, or mortality. Mortality risk among KTRs in the post-vaccination rollout era was almost twice as high as it was in the pre-vaccination rollout era, although there was no statistically significant difference, which might be due to low statistical power. The lack of improved outcomes of KTRs in the postvaccination rollout remains unclear. A combination of suboptimal immunogenic response to vaccination and the Delta variant surge could be a possibility.

Outcomes After Covid-19 Infection in Transplant Recipients

Purpose: The purpose of this study is to evaluate outcomes of readmission, rejection, graft dysfunction, graft failure, and death in SOT recipients (SOTR) after COVID-19 infection. Method(s): We conducted a retrospective cohort study of SOTR diagnosed with COVID-19 infection before 5/1/2021. COVID-19 disease severity was assigned retrospectively by NIH criteria and grouped into asymptomatic/mild and moderate/ severe/critical infection. Data collected included demographics, clinical features, treatment, and outcomes. Bivariate comparisons to evaluate characteristics associated with outcomes were performed with independent group t-tests for continuous variables and Fisher's exact tests for categorical variables. Result(s): 138 SOTR were diagnosed with COVID-19 at a median of 5 (IQR 3-8) years post-transplant with a mean age of 57+/-12 years at diagnosis. Most were kidney or liver recipients (Table 1);49 (36%) had asymptomatic or mild infection. 29 (21%) of SOTR had moderate, 26 (19%) severe, and 31 (22%) critical infection. Disease severity, treatment with steroids or remdesivir did not correlate with rejection. Most graft failures occurred in SOTR with critical (n=12) disease (Table 2). 102 (74%) SOTR were admitted to the hospital for COVID-19 infection, of which 27 (26%) were readmitted more than 2 months after their index hospitalization. Of the readmissions, 5 were for renal complications, 5 infectious, and 7 pulmonary. Among those hospitalized, 13 (13%) SOTR died during the index admission. Among the 27 SOTR who were readmitted, 3 (11%) SOTR died during readmission. The mean time from initial infection to death was 121+/-176 days. Conclusion(s): In this cohort, disease severity was associated with graft failure. Readmissions were frequent more than 2 months after the index admission. Mortality in those who were readmitted remained high. Rejection was relatively infrequent.

ATYPICAL PRESENTATION OF FAT EMBOLISM SYNDROME IN AN IMMUNOCOMPROMISED PATIENT

SESSION TITLE: Systemic Diseases with Deceptive Pulmonary Manifestations SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Fat embolism is a syndrome that can occur during orthopedic procedures or fractures of the long bones, especially the femur and tibia. It can affect multiple organs, including the brain, skin, and lungs, causing the triad of altered mentation, petechiae, and hypoxemia. Here, we present a case of a 54-year-old woman at risk for graft versus host disease (GVHD) who presented with dyspnea a few weeks after an orthopedic procedure. Initial chest radiograph was notable for parenchymal infiltrates, and she was initially treated with antibiotics without improvement. CASE PRESENTATION: A 54-year-old woman with a history of leukemia, stem cell transplantation years ago, GVHD (skin liver, ocular, oral, joints (not lung), with clinical and cytogenetic remission underwent total hip arthroplasty. Two weeks later, she developed lethargy and dyspnea and presented to the emergency department. She was found to have an elevated WBC of x19.5 k/ul (normal 4.1-9.3k/uL) with a left upper lobe consolidation on the chest radiograph (Figure 1). She was treated empirically for pneumonia and discharged with a 7-day course of levofloxacin. Despite completing the course of antibiotics, her dyspnea worsened, and she presented to the emergency department two weeks later with worsening hypoxemia. Computed tomography (CT) of the chest showed bilateral diffuse ground-glass opacities (GGOs) with patchy consolidations in a broncho-vascular distribution (Figure 2). She was negative for COVID-19, Influenza A, B and Legionella urinary antigen. The differential diagnosis included infection and GVHD among others. She underwent bronchoalveolar lavage (BAL). The Gram stain and the culture did not suggest an infection. Pathology from BAL returned significant for reactive bronchial and squamous cells with lipid-laden macrophages. She was started on steroids. Her clinical status improved dramatically, and she was eventually discharged. At a 3-month follow-up her symptoms had improved. Her CT scan also showed significant improvement (Figure 3). DISCUSSION: Our case highlights the successful diagnosis of fat embolism in the lungs in a patient with complicated medical history. Fat embolism usually presents as ground glass opacities. However, the diagnosis was more challenging in this case due to a significant time lapse between her surgery and her presentation to the hospital. She also lacked the other common signs of fat embolism including altered mentation and skin changes. Therefore, other etiologies, such as GVHD, bacterial or viral infection were initially strongly considered. CONCLUSIONS: The diagnosis of fat embolism syndrome condition should still be suspected despite a delay from the initial surgery. Diagnosis in immunocompromised patients requires a detailed workup to rule out other etiologies. Reference #1: Johnson, M. J., & Lucas, G. L. (1996). Fat embolism syndrome. Orthopedics, 19(1), 41-49. Reference #2: Newbigin, K., Souza, C. A., Torres, C., Marchiori, E., Gupta, A., Inacio, J., … & Peña, E. (2016). Fat embolism syndrome: state-of-the-art review focused on pulmonary imaging findings. Respiratory medicine, 113, 93-100. Reference #3: Swiatek, K., Kordic, G., & Jordan, K. (2018). An Unlikely Presentation of Fat Embolism Syndrome. Chest, 154(4), 686A. DISCLOSURES: No relevant relationships by Raheel Anwar No relevant relationships by Boris Medarov

INFECTIONS IN KIDNEY TRANSPLANT RECIPIENTS :SINGLE CENTER EXPERIENCE FROM TERTIARY CARE CENTER IN SOUTH INDIA

Introduction: Infections occurring in the post transplant period are the major cause of morbidity and mortality in renal transplant recipients. Early infections (within the first month) are more likely to be due to nosocomially acquired pathogens, surgical issues, and donor-derived infections. Opportunistic pathogens occur after 6 months, reflects the greater impact of immunosuppressive therapies. Late infections may be secondary to opportunistic pathogens or conventional ones. Methods: It is a retrospective observational study.All hospitalised patients with infections were included between November 2019 to march 2022 excluding covid 19 infections.Infections were categorised based on time line of infection into less than one month, 1-6 months and more than 6 months and sub categorised based on type of organisms and source of infection.All baseline characteristics, labs, microbiological including serology, PCR and cultures, radiological findings and histopathological findings were noted.Complications including graft dysfunction and need for various supports such as O2, ionotropes, ventilator and dialysis and treatment details and in hospital patient outcomes were analysed using descriptive statistics. Results: 53 patients admitted with infection in the given period were included in the study.Among them 88.67% were males and 11.33% females. In the study population 66.03 % underwent live related renal transplant and 33.97% underwent deceased donor transplantation. Mean age of the study population was 35.2 years. There were 118 events of infection identified during the study period.UTI was the most common post-transplant infection and occurred in 36.44 % of total events. There were 13 events of post-transplant infection in the first month. Most common infection in early post-transplant period was UTI, 53.84 % of events of UTI occurred followed by pneumonia in 23.07% of total events. E coli was isolated in 57.14 % of events There were 48 events of infections in the period of 1- 6 months.UTI was the most common infection (37.5 % of total events ) and E coli was the most common organism isolated(44.44 %). Pneumonia was the second commonly occurred event in 18.75 % of total events and Klebsiella was the most common isolated ( 55.56 % ).CMV disease was identified in 10.41% events, 40 % had tissue invasive CMV, 60% presented with cytopenia. There were 57 events of infections after 6 months, UTI was the most common infection(31.57% events) and E coli was the most common organism (44.00%).Pneumonia occurred in 19.29% followed by skin and soft tissue infection (13.94 %)herpes zoster ( 8.75% ) gastroenteritis(7.01%), BKVN (5.26%),oral candidiasis (3.50%)CMV disease (3.50%), tuberculosis(3.5%), meningitis (1.75%) and dengue(1.75%). 95.76% of infectious event was associated allograft dysfunction and 22.64 % of the study population had PTDM. In 15.25 % of events, patients had septic shock at presentation.Amongst them 44.44% had urosepsis, 33.33% had pneumonia, 22.22% had acute gastroenteritis. 18.86 % expired during hospital stay,amongst them 60 % had pneumonia and 30% had urosepsis and 10% had acute gastroenteritis. [Formula presented] [Formula presented] [Formula presented] [Formula presented] Conclusions: Patients who undergo renal transplantation are subjected to immunosuppression which increase the burden of infections in the post-transplant period.Early and accurate diagnosis is the key to prevent morbidity and mortality of renal transplant recipients No conflict of interest

Neoaortoiliac system and cryopreserved human allograft for the treatment of aortic graft infections.

OBJECTIVE: To report and compare neoaortoiliac system reconstruction and cryopreserved human allograft in treating aortic graft infections. METHODS: We retrospectively analysed the data of the patients treated for aorto graft infections between January 2015 and May 2021 in our hospital. The clinical data, diagnostic procedures, and surgical options were evaluated. The primary endpoint of this study was the 30-day and 1-year mortality; secondary endpoints were major postoperative complications. RESULTS: We retrospectively reviewed a series of 31 consecutive patients (28 males; median age 72 years, range, 50-87 years) with aortic graft infection treated with NAIS (n = 20, 65%) or cryopreserved allograft (n = 11, 36%). The clinical presentation included fever attacks in 18 (58%) patients, abdominal pain in 15 (48%) patients, haemodynamic instability in 6 (19%) patients, and haematemesis in 2 (7%) patients. The median operative time of the NAIS was longer than CHA without a statistically significant difference (458 min vs. 359 min, p = .505). The postoperative morbidity for all patients was 81%, with no significant difference between NAIS and CHA groups (85% vs. 73%, p = .638). There was no limb thrombosis of the new reconstructions. Limb loss occurred in 4 (13%) patients, including 2 (10%) NAIS patients and 2 (18%) CHA patients. One NAIS patient developed complications in the form of a distal (femoral) disruption of the vein 15 days after surgery. There were no significant differences between NAIS and CHA groups in ICU stay (12 vs 8 days, .984) but in hospitalization (22 vs 33, p = .033). The most common bacteria isolated were staphylococci strains in 15 (48%). In 13 (36%) patients, candida was positive. The in-hospital 30-day and 1-year mortality for all patients was 16% (5/31) and 29% (9/31), with no significant differences between NAIS and CHA at 30 days (25% vs. 0, p = .133) or 1 year (35% vs. 18%, .429). Five NAIS patients died during the hospital stay; three of them had end-of-life decisions. After a median follow-up of 16 months (1-66 months), 12 (39%) patients died, including 9 patients with NAIS and 3 with CHA reconstructions. The causes of death included overwhelming sepsis in 5 (42%) patients, graft disruption in one (8%) NAIS patient, non-small cell lung cancer in one (8%) patient, COVID-19 in one (8%) patient and unknown causes (8%) in one. CONCLUSIONS: Non-staged neoaortoiliac system reconstruction and cryopreserved human allografts show comparable short- and midterm results for treating aortic graft infections. However, both procedures remain challenging with high morbidity and mortality rates.