Michael Angarone

Diagnostic Yields in Solid Organ Transplant Recipients Admitted With Diarrhea

BACKGROUND Although diarrhea is a frequent complaint among solid organ transplant recipients, the contribution of infectious etiologies remains incompletely defined. We sought to define the etiologies of diarrhea and the yields of testing at our institution. METHODS We performed a retrospective analysis over an 18-month period of hospitalized solid organ transplant recipients. We stratified diarrhea by community onset vs hospital onset of diarrhea. RESULTS We identified 422 admissions (representing 314 unique patients) with community-onset diarrhea, and 112 admissions (representing 102 unique patients) with hospital-onset diarrhea. The majority of community- and hospital-onset diarrheal episodes had no identified etiology (60.9% and 75.9%, respectively; P = .03), yet were also self-limited (91% and 91%, respectively; P = .894). Thereafter, the most frequently encountered infectious etiologies were Clostridium difficile infection (13.3% and 11.8%, respectively), norovirus enteritis (8.2% and 3%), cytomegalovirus disease or colitis (6.3% and 2.7%), and bacterial enterocolitis (0.9% and 0%) (P = .03). In aggregate, these entities represented 93.7% and 90.5% of the identified infectious etiologies, respectively. Protozoan causes were rarely seen. Coinfection, or the simultaneous detection of ≥2 pathogens, occurred in 8 (1.9%) and 2 (1.8%) community- and hospital-onset diarrheal admissions, respectively (P = .99). CONCLUSIONS In solid organ transplant recipients who presented at our institution with diarrhea, approximately one-third had infectious etiologies identified, consisting predominantly of C. difficile, norovirus, cytomegalovirus, and bacterial enterocolitis. Other infectious etiologies were rare.

Fluorescence endoscopy of cathepsin activity discriminates dysplasia from colitis

Background:Surveillance colonoscopy using random biopsies to detect colitis-associated cancer (CAC) suffers from poor sensitivity. Although chromoendoscopy improves detection, acceptance in the community has been slow. Here, we examine the usefulness of near infrared fluorescence (NIRF) endoscopy to image molecular probes for cathepsin activity in colitis-induced dysplasia. Methods:In patient samples, cathepsin activity was correlated with colitis and dysplasia. In mice, cathepsin activity was detected as fluorescent hydrolysis product of substrate-based probes after injection into Il10−/− colitic mice. Fluorescence colonoscopy and colonic whole-mount imaging were performed before complete sectioning and pathology review of resected colons. Results:Cathepsin activity was 5-fold and 8-fold higher in dysplasia and CAC, respectively, compared with areas of mild colitis in patient tissue sections. The signal-to-noise ratios for dysplastic lesions seen by endoscopy in Il10−/− mice were 5.2 ± 1.3 (P = 0.0001). Lesions with increased NIRF emissions were classified as raised or flat dysplasia, lymphoid tissue, and ulcers. Using images collected by endoscopy, a receiver operating characteristic curve for correctly diagnosing dysplasia was calculated. The area under the curve was 0.927. At a cutoff of 1000 mean fluorescence intensity, the sensitivity and specificity for detecting dysplasia were 100% and 83%, respectively. Analysis revealed that focally enhanced NIRF emissions derived from increased numbers of infiltrating myeloid-derived suppressor cells and macrophages with equivalent cathepsin activity. Conclusions:These studies indicate that cathepsin substrate-based probe imaging correctly identifies dysplastic foci within chronically inflamed colons. Combined white light and NIRF endoscopy presents unique advantages that may increase sensitivity and specificity of surveillance colonoscopy in patients with CAC.

BK Virus Replication and Nephropathy After Alemtuzumab‐Induced Kidney Transplantation

BK virus nephropathy (BKVN) is a recognized cause of graft failure in kidney transplant recipients. There are limited data on the epidemiology of BK virus (BKV) infection after alemtuzumab induction. By clinical protocol, the kidney transplant recipients at our center were screened with BKV plasma PCR monthly for the first 4 months posttransplant then every 2–3 months for 2 years. A single center retrospective cohort study of all kidney transplant recipients from January 2008 to August 2010 was conducted to determine incidence and outcomes of BKV infection. Descriptive statistics and Kaplan–Meier analysis was performed. Of 666 recipients, 250 (37.5%) developed viruria, 80 (12%) developed viremia and 31 (4.7%) developed BKVN at a median of 17, 21 and 30 weeks, respectively. Induction with alemtuzumab did not significantly affect incidence of BKVN. Increased recipient age, African American race, acute graft rejection and CMV infection were significantly associated with the development of BKVN in multivariate analysis. The incidence of BK viruria, viremia and nephropathy was not significantly different among kidney transplant recipients who received alemtuzumab induction compared to patients receiving less potent induction.

Diarrhea in solid organ transplant recipients.

Purpose of review Diarrhea is a common complaint in the solid organ transplant recipient. Unlike the immune-competent patient, diarrhea in an organ transplant recipient may result in dehydration, increased toxicity of medications, and rejection. There is a wide range of causes for diarrhea in transplant recipients, but the most common causes are Clostridium difficile infection, cytomegalovirus, and norovirus. This review will focus on new epidemiology data as to the cause of diarrhea in the transplant population. Recent findings Recent data have identified C. difficile, cytomegalovirus, and norovirus as important causes of diarrhea in this population, and management should be focused on these causes. Newer diagnostic platforms (such as PCR) are being evaluated, which may help in identification of the cause of diarrhea. Summary New epidemiologic data and new testing techniques offer an opportunity for research into better testing strategies for transplant patients with diarrhea. These newer testing strategies may offer better insight into the cause of diarrhea and more appropriate treatment for this illness.

Ganciclovir-resistant cytomegalovirus infection in solid organ transplant recipients: a single-center retrospective cohort study

Ganciclovir‐resistant cytomegalovirus (GCV‐R CMV) is an emerging challenge among solid organ transplant (SOT) recipients. The literature suggests that about 1% of abdominal transplant recipients develop GCV‐R CMV infection. The epidemiology and outcome of GCV‐R CMV in SOT recipients who have received alemtuzumab induction is not well described.

Norovirus in Transplantation

Noroviruses are among the most common cause of diarrhea in transplant recipients. The clinical spectrum of norovirus infection after transplant is increasingly being recognized. As substantial morbidity is now associated with norovirus infections in this population; the quest for rapid diagnostic modalities and newer therapies has expanded. Transplant recipients with norovirus infection are at risk for several complications, including protracted illness with malnutrition, organ failure, and chronic viral shedding. This review summarizes the current knowledge on the epidemiology, complications, diagnosis, and treatment of norovirus infection in the transplant setting.

Epidemiology and prevention of viral infections in patients with hematologic malignancies.

Viral infections are some of the most frequent complications in patients with hematologic malignancies are viral infections. Infections caused by cytomegalovirus, herpes simplex virus, varicella zoster virus, hepatitis B virus and influenza virus are associated with high morbidity and mortality in this vulnerable population. Fortunately, a growing number of antiviral medications and vaccines are allowing for more effective prophylaxis against these pathogens. This article reviews the epidemiology and prophylactic strategies available for these opportunistic viral pathogens.

Fungal Infections in Cancer Patients

Invasive fungal infections (IFI) have become a leading cause of morbidity and mortality in cancer patients. Infections with these organisms are often difficult to diagnose and treat. Appropriate and timely diagnosis requires a high index of suspicion and invasive procedures, including biopsy, to confirm the diagnosis. Treatment may be difficult, secondary to variable susceptibility and difficulty with exact and specific characterization of the fungal pathogen. The pathogens that are seen range from yeasts to invasive molds. Fortunately newer, noninvasive diagnostic techniques are available to aid in the diagnosis and treatments have become better tolerated and more efficacious.

Purpureocillium lilacinum tattoo-related skin infection in a kidney transplant recipient

Purpureocillium lilacinum is an emerging pathogenic mold among immunocompromised hosts that causes cutaneous infections related to skin breakdown. We present the first reported case of P. lilacinum tattoo‐related skin infection, to our knowledge. A kidney transplant recipient recently treated for acute cellular rejection presented with skin papules overlying a tattoo. Diagnosis was confirmed on culture, histology, and 18S ribosomal RNA polymerase chain reaction. The morphological features on culture characteristic of P. lilacinum included violet colonies on malt extract agar, long tapering brush‐like phialides, and elliptical conidia attached in chains. P. lilacinum has intrinsic resistance to many antifungal agents including amphotericin B, but voriconazole and posaconazole have good in vitro activity. The patient was treated with voriconazole with subsequent resolution of the papules after 3 months of therapy.

Lymphopenia is associated with late onset Pneumocystis jirovecii pneumonia in solid organ transplantation

Pneumocystis jirovecii pneumonia (PJP) affected 5%‐15% of solid organ transplant (SOT) recipients prior to universal prophylaxis, classically with trimethoprim‐sulfamethoxazole (TMP‐SMX). Guidelines generally recommend 6‐12 months of prophylaxis post‐SOT, yet optimal duration and robust PJP risk stratification have not been established.