Small Bowel Transplant Recipients Research Articles

A metagenomic prospective cohort study on gut microbiome composition and clinical infection in small bowel transplantation.

Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1-10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.

Management of COVID-19 Infection in a Small Bowel Transplant Recipient: A Case Report

The COVID-19 pandemic has caused millions of people to become infected worldwide. Some patients may have disease progression and may need treatment with an anti-COVID-19 agent, hospitalization, and even intensive care. The risk factors for disease progression include old age, diabetes mellitus, pulmonary disease, cardiac disease, immunodeficiency, and immunosuppressant treatment. Therefore, managing COVID-19 infection in transplant patients under immunosuppressant treatments needs specific consideration, especially the side effects of anti-COVID-19 agents and the interaction between immunosuppressants and anti-COVID-19 agents. In this report, we present the case of a small bowel transplant patient who had a COVID-19 infection. The patient was initially treated for paxlovid, and she developed bloody stools and dizziness. The treatment was then changed to molnupiravir without discontinuation of tacrolimus. The patient recovered smoothly after a 5-day treatment with molnupiravir. Here, we discuss the management experience of such patients and review the relevant literature.

Multidrug-resistant Klebsiella Pneumoniae Infection Led to Resection of the Graft in a Small Bowel Transplant Recipient: A Case Report and Review of the Literature

Infection due to multidrug-resistant Klebsiella pneumoniae is a common cause of graft resection after small bowel transplantation. We report a failed case in which the intestinal graft was resected 18 days after the operation due to postoperative infection with multidrug-resistant K pneumoniae and a literature review of other common causes of small bowel transplantation failure have been reported. A female, 29 years of age, underwent partial living small bowel transplantation for short bowel syndrome. After the operation, the patient was infected with multidrug-resistant K pneumoniae, even though various anti-infective regimens were employed. It further developed into sepsis and disseminated into intravascular coagulation, leading to exfoliation and necrosis of the intestinal mucosa. Finally, the intestinal graft had to be resected to save the patient's life. Multidrug-resistant K pneumoniae infection often affects the biological function of intestinal grafts and can even lead to necrosis. Other common causes of failure, including postoperative infection, rejection, post-transplantation lymphoproliferative disorder, graft-vs-host disease, surgical complications, and other related diseases, were also discussed throughout the literature review. Pathogenesis due to diverse and interrelated factors makes the survival of intestinal allografts a great challenge. Therefore, only by fully understanding and mastering the common causes of surgical failure can the success rate of small bowel transplantation be effectively improved.

A Case Report of Successful Use of Twice-Daily Letermovir in the Treatment of Resistant Cytomegalovirus in a Small Bowel Transplant Recipient

Cytomegalovirus (CMV) is considered one of the most notable pathogens that affect patients after solid organ transplantation (SOT), especially small bowel transplant patients with a risk of high mortality rate. Its management relies historically on the use of CMV DNA polymerase inhibitors (namely, ganciclovir and valganciclovir). Second-line options include foscarnet and cidofovir, which are highly nephrotoxic and thus less preferred and only used in ganciclovir intolerance or resistance cases. Letermovir is a novel antiviral agent approved for CMV prophylaxis in hematopoietic stem cell transplant, but not for SOT (neither for prophylaxis nor for treatment). We report the first case on the successful use of letermovir in treating CMV disease in a small bowel transplant patient who failed to achieve viral clearance due to ganciclovir resistance and severe intolerance to foscarnet.

Invasive Pulmonary Aspergillosis Complicating Noninfluenza Respiratory Viral Infections in Solid Organ Transplant Recipients.

BackgroundInvasive pulmonary aspergillosis (IPA) is increasingly recognized as a complication of severe influenza and coronavirus disease 2019. The extent to which other respiratory viral infections (RVIs) predispose to IPA is unclear. MethodsWe performed a retrospective review of IPA occurring within 90 days of respiratory syncytial virus (RSV), parainfluenza, or adenovirus infections (noninfluenza respiratory viral infections [NI-RVIs]) in patients who underwent solid organ transplant between 1/15/2011 and 12/19/2017. ResultsAt a median post-transplant follow-up of 43.4 months, 221 of 2986 patients (7.4%) developed 255 RSV, parainfluenza, or adenovirus infections. IPA complicating these NI-RVIs was exclusively observed in lung and small bowel transplant recipients, in whom incidence was 5% and 33%, respectively. Cumulative prednisone doses >140mg within 7 days and pneumonia at the time of NI-RVI were independent risk factors for IPA (odds ratio [OR], 22.6; 95% CI, 4.5–112; and OR, 7.2; 95% CI, 1.6–31.7; respectively). Mortality at 180 days following NI-RVI was 27% and 7% among patients with and without IPA, respectively (P = .04). ConclusionsIn conclusion, IPA can complicate RSV, parainfluenza, and adenovirus infection in lung and small bowel transplant recipients. Future research is needed on the epidemiology of IPA complicating various RVIs. In the interim, physicians should be aware of this complication.

P-18: COVID-19 in Small Bowel Transplant Recipients: A Single Center Experience

Introduction: Coronavirus disease 2019 (COVID-19) outbreak posed unique challenges for immunosuppressed patients. Little is known about the clinical course and immunosuppression management of this novel infection in intestinal transplant recipients. Methods: We experienced 6 adult intestinal transplant recipients who had a positive swab test of COVID-19 and symptoms. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. Results: Median age was 53 years (range 30-71). They had 3 liver-free composite allografts, 2 isolated intestine, and 1 intestine-kidney with median time from transplant of 8 years (range 4-12). Maintenance immunosuppressive therapy was tacrolimus/steroid in 4, and tacrolimus monotherapy in 2 patients. The most common symptom was cough (n=5) followed by fever (n=3) and dyspnea (n=3). All had ground glass opacities on computed tomography. Four patients were admitted to our institution but two were managed at local hospital due to difficulty of transportation. Immunosuppression therapy was never suspended and was reduced for one patient. Pharmacological therapy consisted in remdesivir and steroids for 4 recipients (67%) associated with convalescent plasma in 2 cases (33%) plus tocilizumab in 1 case (17%), and steroids for 2 patients (33%) associated with convalescent plasma in 1 case (17%). Two patients required intubation for acute respiratory distress syndrome. One patient received antibiotics for superimposed bacterial pneumonia. Mean white blood cells and lymphocyte count were 4.72±0.6 k/uL and 0.96±0.65 k/uL at presentation, respectively. Mean D-Dimer, C-reactive protein and ferritin were 740±160 ng/ml, 4.1±5 mg/dl and 249±149 ng/ml, respectively at presentation, with a peak of 1255±785 mg/ml, 10.9±8 mg/dl and 630±318 ng/ml, respectively. No significant changes were noted in liver and renal function. Before discharge, all patients underwent ileoscopy and allograft biopsies with no evidence of inflammation/rejection. Mean hospital stay was 36±21 days. Death occurred in 2 patients (33%) who were managed at local hospital. No recurrence was noted with mean follow up of 90 days. Conclusions: We treated intestinal transplant recipients symptomatic for COVID-19 without immunosuppression interruption. No increased inflammation or rejection was noted in the intestinal grafts. Aggressive treatment of COVID-19 infection should be granted under expertise of intestinal transplant and transplant infectious disease team.

Therapeutic Plasma Exchange in Small-Bowel Transplant Recipients

Therapeutic plasma exchange (TPE) is an important adjunct therapy to reduce levels of donor-specific antibodies (DSAs) associated with antibody mediated rejection (AMR) in solid organ transplant recipients, especially kidney recipients. The purpose of this study was to examine the effect of TPE on DSAs and clinical/pathologic evidence of rejection in small bowel transplant recipients.

A 9-Year-Old Male with Barth Syndrome and a Cardiac Transplant Presenting with Hyperviscosity Syndrome Caused By EBV-Negative Plasmacytic PTLD

Posttransplant lymphoproliferative disorders (PTLD) are a spectrum of disorders characterized by lymphoid or plasmacytic proliferation secondary to extrinsic immunosuppression in solid organ transplant (SOT) or hematopoietic transplant recipients. According the 2016 revision of World Health Organization (WHO) classification, PTLD ranges from early lesion (mononucleosis-like) lymphoid hyperplasia or plasmacytic hyperplasia, polymorphic, monomorphic to classical Hodgkin lymphoma PTLD (Swerdlow et. al. Blood 2016). The incidence of PTLD in the pediatric population is closely associated with the type of transplanted organ, with the highest incidence in lung and small bowel transplant recipients due to chronic, iatrogenic immunosuppression. While Epstein-Barr Virus (EBV) is the key driver of abnormal lymphocytic proliferation in the majority of PTLDs, EBV-negative PTLD is a distinct subtype. We hereby report a 9-year-old boy with Barth syndrome, a rare genetic syndrome caused by a TAZ mutation, characterized by dilated cardiomyopathy, skeletal myopathy, neutropenia, and short stature. He required a heart transplant for left ventricular non-compaction cardiomyopathy at 11 months of age and presented with lower GI bleeding, acute-onset anemia, somnolence, retinal hemorrhages, and increased serum viscosity eight years post transplant. Workup was significant for hyperimmunoglobulinemia with elevated IgA and IgG, and serum protein electrophoresis (SPEP) showed two monoclonal bands (IgA Lambda and IgG Kappa) and an M spike. He was treated with plasmapheresis, and his symptoms improved significantly. Further workup with PET/CT scan showed diffuse lymphadenopathy of cervical, mediastinal, axillary, abdominal, and inguinal lymph nodes. Axillary lymph node biopsy was done, demonstrating a nondestructive morphology with an increase in plasma cells expressing excess lambda light chain and IgA; these abnormal cells were CD20 negative and CD138 positive, suggesting a clonal process. Cytogenetic fluorescence in situ hybridization (FISH) showed loss of TP53. Serum EBV detection by PCR and EBER staining by immunohistochemistry (IHC) on lymph node pathology were negative. Bone marrow biopsy showed a hypocellular marrow with trilineage hematopoiesis and 5-10% CD138 positive plasma cells. Combined, these studies were consistent with the diagnosis of early onset, nondestructive, plasmacytic PTLD. The patient was treated with a multiple myeloma-type therapy with dexamethasone and bortezomib (Short et. al. J Pediatr Hematol Oncol 2016), in addition to reduced immunosuppression consisting of low dose tacrolimus. Repeat PET/CT scan after 2 cycles of therapy showed resolution of previous PET-avid lesions. Stem cell collection was performed after 3 cycles in case of relapsed or recurrent disease. He completed 5 cycles of therapy with no complications. Unfortunately, the patient's end of treatment PET/CT scan was significant for a new mediastinal mass and multiple intraabdominal lymph nodes. Lymph node biopsy showed a lymphoplasmacytic infiltrate, which was IgA and lambda positive. The cells showed plasmacytoid features, but in contrast to the initial biopsy at diagnosis, there was marked CD20 positivity (image attached). This recurrence was most suggestive of a marginal zone lymphoma like PTLD (Galera et. al. Am J Surg Pathol 2020). He was initiated on therapy with rituximab and bendamustine. He is currently status post 2 treatment cycles and doing well. We continue to discuss the utility of autologous bone marrow transplant in this case, although the risks and benefits will have to be weighed carefully in a child who is prone to develop infections and complications from Barth Syndrome. We would like to share this case of EBV negative, plasmacytic PTLD with relapsed marginal zone lymphoma type PTLD to highlight the heterozygous pathologies of PTLD in children, and to share our experience of treating in the absence of standard protocol due to the rarity of this diagnosis. Figure Disclosures No relevant conflicts of interest to declare.

553 Clinical characteristics of acute graft-versus-host disease in small bowel and multi-visceral transplant recipients

Acute graft-versus-host disease (aGVHD) following stem cell transplantation is characterized by rash, liver dysfunction, and diarrhea. Although aGVHD is uncommon following solid organ transplantation, we find higher rates of aGVHD after intestinal (ITx) and multi-visceral transplantation (MVT). In these cases we find a unique presentation as the donor liver (if present) and intestine are spared, leaving skin as the main target. Between 2013 and 2019, we diagnosed 17 cases of aGVHD following ITx (n=9) and MVT including both intestine and liver (n=8). Median time to onset of aGVHD was 37 days. Erythema on the trunk, palms, or both was the most common presenting skin finding (15/17 patients). All patients had skin biopsies at the time of diagnosis. Patients presented with grade 1 (7/17), grade 2 (8/17), grade 3 (1/17), and grade 4 (1/17) aGVHD. Peripheral blood chimerism studies obtained in 11 patients revealed donor CD3+ lymphocytes in 5 (45%). Two patients had passenger lymphocyte syndrome, and partial donor stem cell engraftment was diagnosed in a third patient. Native GI tract involvement (usually rectosigmoid), was found in 7/17 patients; other sites included bone marrow, and native liver. In all, 6/17 patients had no evidence of extra-cutaneous aGVHD. Treatment strategies included systemic and topical corticosteroids, anti-thymocyte globulin, extracorporeal photopheresis, and/or JAK inhibitors. Complications of immunosuppression including opportunistic infections (aspergillosis and toxoplasmosis) and post-transplant lymphoproliferative disorder occurred in 7/17 patients. In summary, rash is typically the first, and may be the only, manifestation of aGVHD following luminal organ transplants. Diagnosis may be aided by time of onset of cutaneous manifestations, extra-cutaneous signs, and peripheral blood chimerism.

A multicenter study to define the epidemiology and outcomes of Clostridioides difficile infection in pediatric hematopoietic cell and solid organ transplant recipients.

Hematopoietic cell transplant (HCT) and solid organ transplant (SOT) recipients are at increased risk for Clostridioides difficile infection (CDI). We conducted a multicenter retrospective study to describe the incidence of CDI in children transplanted between January 2010 and June 2013. Nested case-control substudies, matched 1:1 by transplant type, institution, patient age, and time of year (quartile) of transplant, identified CDI risk factors. Cohorts included 1496 HCT and 1090 SOT recipients. Among HCT recipients, 355 CDI episodes were diagnosed in 265 recipients (18.2%). Nested case-control study identified prior history of CDI (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.7), proton pump inhibitors (PPIs; OR 2.1, 95% CI 1.3-3.4), and exposure to third- (OR 2.4, 95% CI 1.4-4.2) or fourth-generation (OR 2.1, 95% CI 1.2-3.7) cephalosporins as risk factors. Notably, fluoroquinolone exposure appeared protective (OR 0.6, 95% CI 0.3-0.9). Ninety-two episodes of CDI were diagnosed among 79 SOT recipients (7.3%), and exposure to PPIs (OR 2.4, 95% CI 1.1-5.4) and third-generation cephalosporin therapy (OR 3.9, 95% CI 1.4-10.5) wereidentified as risk factors. Strategies to decrease PPI use and changes in the class of prophylactic antibiotics may impact CDI incidence and warrant further study.

P2.37: Variance in peripheral blood absolute lymphocyte counts as a predictor of exfoliative rejection in small bowel transplant recipients

Introduction: Exfoliative rejection (ER) following small bowel or combined liver/small bowel transplantation is an extreme form of graft rejection associated with significant morbidity and mortality with high rates of allograft removal. Re-transplantation after exfoliative rejection has demonstrated low success rates. During the outset of rejection episodes, few predictors differentiate between ER and non-exfoliative rejection. Aggressive immunosuppression with antibody based therapy and early surgical intervention remain the cornerstone of management. Our treatment protocol for acute cellular rejection requires failure of a steroid burst before antithymocyte antibodies are started, but excessive delay in initiation of antibody therapy may result in exfoliation and graft loss. Our objective is to determine if peripheral blood lymphocyte counts can predict progression to ER. Methods: All patients undergoing a small bowel or combined liver/small bowel transplant at Cincinnati Children’s Hospital Medical Center (CCHMC) were retrospectively reviewed for this study. All with biopsy proven acute cellular rejection and peripheral blood lymphocyte enumeration were included. The histologic severity of the rejection episode and lymphocyte counts prior to and during the rejection episode were collected. Results: Electronic medical record changes permitted review of 38 of 55 transplants since 2003. Twenty-nine patients (76%) had histologic rejection greater than Grade 1. Of all patients, 5 (13%) had ER. Early biopsies eventually progressing to ER had higher peripheral blood absolute lymphocyte counts (ALC) prior to rejection than did biopsies diagnostic of rejection failing to progress (960 vs 600, p = 0.02). More importantly, peripheral blood lymphocyte counts also rose much more dramatically in those whose biopsies subsequently progressed to exfoliation than in those whose rejection did not progress (1179% vs 81%, p <0.001). Conclusion: Based on these data, absolute lymphocyte count, specifically, the variance in ALC is associated with progression from low grade rejection to ER. Although, there was a statistically significant difference in the ALC in patients with exfoliation, substantial variance from baseline may be more important than the absolute number in predicting ER, thereby justifying early use of antithymocyte globulin or alemtuzumab.

P4.32: Digestive autonomy in patients with intestinal failure after small bowel transplantation

Introduction: Home parenteral nutrition (HPN) and all the complications related to it, used to be the only option in patients with intestinal failure. Nowadays small bowel transplant (SBT) is an answer to these patients. Methods: From December 2004 to January 2019 we have assessed 105 patients as potential candidates, the majority of them not eligible; and have performed 31 transplants in 29 patients (21 IT and 8 MVT). Results: Short bowel syndrome (SBS) was found in 60% (18/29) of the patients. Potential candidates for SMT were malnourished, with a mean pretransplant BMI of 22.2, average weight of 61.6kg and pre albumin values around 21.7mg/dl. 64% of the patients required total HPN before the SBT and almost 86% had several HPN-related complications due to it (6% thrombosis of major venous access, 37% catheter -related infections, 28% sepsis, refractory balance alterations. After SBT the patients in our study reached a mean BMI of 23.7,mean weight of 67.8kg and pre albumin values around 26.7mg/dl. All recipients achieved satisfactory oral nutritionat about post-transplant day 12. Almost 80% of the patients required parenteral nutrition support during the first two months post-transplantation. SBT recipients will need some form of parenteral nutrition support for an average period of 27 months including the time before and after the SBT. One year after undergoing transplantation, all recipiets will achieve a complete digestive autonomy and only 8,3% will need fluid replacement therapy. Conclusions: Small bowel transplantation is a life-saving procedure for patients with intestinal failure who develop complications related to parenteral nutrition, and it is the most effective treatment in terms of complete digestive autonomy acquisition for these patients

Candida infections in solid organ transplantation: Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.

These updated guidelines from the American Society of Transplantation Infectious Diseases Community of Practice provide recommendations for the diagnosis and management of Candida infections in solid organ transplant recipients. Candida infections manifest primarily as candidemia and invasive candidiasis and cause considerable morbidity and mortality. Early diagnosis and initiation of treatment are necessary to reduce mortality. For both candidemia and invasive candidiasis, an echinocandin is recommended for initial therapy. However, early transition to oral therapy is encouraged when patients are stable and the organism is susceptible. Candida prophylaxis should be targeted for high-risk patients in liver, small bowel, and pancreas transplant recipients. Future research should address which patient groups may benefit most from preventative antifungal therapy strategies.

PTLD Involving the Colon Graft in Small Bowel Transplant Recipient

Intestinal transplant is indicated in those who have intestinal failure with resultant life-threatening complications. Complications from intestinal transplant include surgical complications eg. graft thrombosis, rejection and complications due to a high immunosuppressive requirement eg. atypical viral/fungal infections and PTLD. We present a 23-year-old white female with combined small bowel and colonic transplant 11 months ago due to intestinal failure from small bowel volvulus. She was diagnosed with PTLD with diffuse large B-cell lymphoma 1 month ago after presenting with painless LAD. She was on tacrolimus 4 mg BID, 2000 mg/day MMF, and 5 mg/day prednisone. Her EBV DNA was > 2 million copies/ml at the time of diagnosis. She underwent reduction in immunosuppression followed by 1 cycle of R-CHOP and presented with new-onset GI bleeding. EGD to jejuno-jejunal anastomosis was unremarkable but colonoscopy showed a large amount of fresh blood in the colon and ileum. The visualization of colonic mucosa was limited but CTA showed positive luminal extravasation just beyond jejuno-jejunal anastomosis which was successfully treated with embolization. Follow-up colonoscopy to evaluate for small bowel and colonic graft rejection showed normal small bowel and colonic allograft and multiple non-bleeding discreet raised yellowish black-crusted sub-epithelial nodules obliterating nearby normal colonic vasculature in native colon. Pathology showed an atypical lymphoid infiltrate with necrosis in the native colon confirmed to be monomorphic PTLD (positive for CD79a, Pax5, Mum-1, CD 20, EBV-LMP, negative CD3, Ki-67 of 70%). Her abdominal CT scan showed progressive disease burden with extensive liver metastasis. Despite treatment, her hospital course was complicated by neutropenic fever, septic shock, malignant ascites, and spontaneous intracranial hemorrhage from CNS involvement of PTLD. Therefore, no escalation of treatment was discussed and she was made comfort care. The risk of PTLD is high in intestinal transplant recipients due to high immunosuppression requirement (tacrolimus and MMF) and occur in 15% of adults and 20% of children. Colonic involvement of PTLD may portend the aggressive nature of PTLD and be seen more in disseminated or multiple organs involvement. This case highlights a variety of symptoms of PTD in an intestinal transplant recipient from initial presentation with painless LAD followed by an obscure overt GI bleeding due to colonic PTLD

Epidemiological investigation of Candida species causing bloodstream infection in paediatric small bowel transplant recipients.

Small bowel transplantation (SBT) can be a life-saving medical procedure. However, these recipients experience high risk of bloodstream infections caused by Candida. This research aims to characterise the SBT recipient gut microbiota over time following transplantation and investigate the epidemiology of candidaemia in seven paediatric patients. Candida species from the recipients' ileum and bloodstream were identified by internal transcribed spacer sequence and distinguished to strain by multilocus sequence typing and randomly amplified polymorphic DNA. Antifungal susceptibility of bloodstream isolates was determined against nine antifungals. Twenty-two ileostomy samples harboured at least one Candida species. Fungaemia were caused by Candidaparapsilosis, Candidaalbicans, Candidaglabrata, Candidaorthopsilosis and Candida pelliculosa. All but three bloodstream isolates showed susceptibility to all the antifungals tested. One C.glabrata isolate showed multidrug resistance to itraconazole, amphotericin B and posaconazole and intermediate resistance to caspofungin. Results are congruent with both endogenous (C.albicans, C.glabrata) and exogenous (C.parapsilosis) infections; results also suggest two patients were infected by the same strain of C.parapsilosis. Continuing to work towards a better understanding of sources of infection-particularly the exogenous sources-would lead to targeted prevention strategies.

Tu1865 Post-Transplant Lymphoproliferative Disorder in Small Bowel Transplant Recipients: A Single Center Experience

Tu1865 Post-Transplant Lymphoproliferative Disorder in Small Bowel Transplant Recipients: A Single Center Experience

Adenovirus Enteritis in Adult Small Bowel Transplant Recipients, a Challenging Diagnosis With Critical Clinical Relevance: A Report of 2 Cases

Adenovirus enteritis (AE) is uncommon in adult small bowel transplant recipients but can be associated with increased morbidity and mortality. We present 2 cases of AE with contrastingly different outcomes. The first patient was a 49-year-old man with short bowel syndrome (SBS) secondary to multiple surgeries for Crohn disease and initial good evolution. 10 months after isolated small bowel transplant, …

Adenovirus disease in six small bowel, kidney and heart transplant recipients; pathology and clinical outcome.

Adenoviruses are emerging as important viral pathogens in hematopoietic stem cell and solid organ transplant recipients, impacting morbidity, graft survival, and even mortality. The risk seems to be highest in allogeneic hematopoietic stem cell transplant recipients as well as heart, lung, and small bowel transplant recipients. Most of the adenovirus diseases develop in the first 6 months after transplantation, particularly in pediatric patients. Among abdominal organ recipients, small bowel grafts are most frequently affected, presumably due to the presence of a virus reservoir in the mucosa-associated lymphoid tissue. Management of these infections may be difficult and includes the reduction of immunosuppression, whenever possible, combined with antiviral therapy, if necessary. Therefore, an awareness of the pathology associated with such infections is important in order to allow early detection and specific treatment. We reviewed six transplant recipients (small bowel, kidney, and heart) with adenovirus graft involvement from two institutions. We sought to compare the diagnostic morphology and the clinical and laboratory findings. The histopathologic features of an adenovirus infection of the renal graft and one native kidney in a heart transplant recipient included a vaguely granulomatous mixed inflammatory infiltrate associated with rare cells showing a cytopathic effect (smudgy nuclei). A lymphocytic infiltrate, simulating T cell rejection, with admixture of eosinophils was also seen. In the small bowel grafts, there was a focal mixed inflammatory infiltrate with associated necrosis in addition to cytopathic effects. In the heart, allograft adenovirus infection was silent with no evidence of inflammatory changes. Immunohistochemical stain for adenovirus was positive in all grafts and in one native kidney. All patients were subsequently cleared of adenovirus infection, as evidenced by follow-up biopsies, with no loss of the grafts. Adenovirus infection can involve allografts as well as native organs in solid organ transplant recipients. Infection is associated with variable necrosis and acute inflammation, in addition to a rejection-like infiltrate. Hematuria in non-renal solid organ transplant recipients may be associated with adenovirus nephritis and clinically silent graft involvement. Prompt diagnosis (aided by immunohistochemistry (IHC) and serology), with specific treatment, can prevent graft loss.

Incidence of bloodstream infections in small bowel transplant recipients receiving selective decontamination of the digestive tract: A single-center experience.

Pediatric patients undergoing small bowel transplantation are susceptible to postoperative CLABSI. SDD directed against enteric microbes is a strategy for reducing CLABSI. We hypothesized that SDD reduces the frequency of CLABSI, infections outside the bloodstream, and allograft rejection during the first 30 days following transplant. A retrospective chart review of 38 pediatric small bowel transplant recipients at CCHMC from 2003 to 2011 was conducted. SDD antimicrobials were oral colistin, tobramycin, and amphotericin B. The incidence of CLABSI, infections outside the bloodstream, and rejection episodes were compared between study periods. The incidence of CLABSI did not differ between study periods (6.9 CLABSI vs. 4.6 CLABSI per 1000 catheter days; p = 0.727), but gram positives and Candida predominated in the first 30 days. Incidence of bacterial infections outside the bloodstream did not differ (p = 0.227). Rejection occurred more frequently during the first month following transplant (p = 0.302). SDD does not alter the incidence of CLABSI, bacterial infections outside the bloodstream, or allograft rejection in the immediate 30 days post-transplantation. However, SDD does influence CLABSI organism types (favoring gram positives and Candida) and Candidal infections outside the bloodstream.

Autoantibodies to red blood cell antigens occur frequently with hemolysis among pediatric small bowel transplant recipients: clinical implications and management.

Reports have linked pediatric solid organ transplant recipients with the development of hemolytic autoimmune antibodies, especially in the setting of the immunosuppressant tacrolimus. This study aims to identify whether these observations also occurred at an institution that frequently performs pediatric multivisceral transplants and to characterize the treatment and outcome. Chart review was performed on all patients with RBC autoantibodies. Laboratory and clinical data were used to identify hemolysis. For transplant recipients with RBC autoantibodies, the type of transplant and outcome of the AIHA were profiled. One hundred twenty-eight patients were identified with RBC autoantibodies, of which 22 patients were solid organ transplant recipients, including 18 SB graft recipients. Sixteen of the 18 had evidence of hemolysis. The incidence rate of AIHA in this population is estimated to be 10%, resulting in significant cost. Treatment included immunosuppressant modulation, steroids, IVIG, and plasma exchange, with 12 of the 16 patients responding. RBC autoantibodies occur in up to 10% in pediatric SB transplant recipients, with high cost of obtaining compatible blood. Neither tacrolimus nor receipts of a donor spleen were associated with the development of AIHA. Treatment using steroids and IVIG appears to be effective.