Donor-derived renal allograft mucormycosis in a combined liver and kidney transplantation: Case report and review of the literature.

Mucormycosis infrequently may present with isolated renal involvement. Among solid organ transplant recipients, renal allograft mucormycosis has been most often associated with medical tourism or transplantation outside of the western world. We report a case of an HIV/HCV co-infected woman who underwent simultaneous liver and kidney transplantation with a Public Health Service increased risk donor organ. 16 days after transplant, she developed massive hematuria and was found to have renal allograft Rhizopus spp. involvement, we surmise to have been from donor-derived infection. Therapy included nephrectomy, debridement, liposomal amphotericin B, and posaconazole with survival. We reviewed PubMed indexed, English-language cases of isolated renal mucormycosis in general, in HIV/AIDS, and from donor-derived renal allograft infections.

Safety and efficacy of chronic suppressive azole therapy for endemic fungal infections in solid organ transplant recipients.

BACKGROUND: Although the research is limited, treatment guidelines recommend lifelong suppressive azole therapy for disseminated endemic fungal infection (EFI) after solid organ transplantation (SOT). Suppressive azole therapy may prevent EFI recurrence at the risk of hepatotoxicity and drug interactions. We present real-world safety and effectiveness data of chronic suppressive azole therapy for EFI in SOT recipients over a 10-year period at a single comprehensive transplant center. METHODS: A retrospective analysis was conducted of SOT recipients diagnosed with EFI from January 1, 2005, to May 1, 2015. Chronic suppressive azole therapy was defined as treatment for more than 12 months after diagnosis. Effectiveness of suppression was defined as preventing EFI reactivation. Safety endpoints included adverse reactions and drug interactions. RESULTS: Over a 10-year period, 28 SOT recipients were diagnosed with EFI: 16 histoplasmosis, 9 blastomycosis, and 3 coccidioidomycosis. Eighteen (64%) patients were treated with chronic suppressive azole therapy for a median length of 36 months (range 15-90). One patient had an adverse drug interaction requiring azole discontinuation. There were no episodes of azole-related hepatotoxicity, toxicity from antirejection medication, or EFI reactivation. CONCLUSIONS: Chronic suppressive azole therapy was safe and effective in preventing reactivation of EFI in SOT recipients.

Cytomegalovirus infection in heart transplantation: A single center experience.

BACKGROUND: Cytomegalovirus (CMV) infection remains a major complication after heart transplantation with varying prophylaxis strategies employed. We sought to determine the impact of valganciclovir (VGC) duration on the epidemiology of CMV infections after heart transplantation. METHODS: We performed a prospective cohort study of CMV donor (D) or recipient (R) seropositive heart transplant recipients from 2005 to 2012 who completed VGC prophylaxis, ranging from 3 to 12 months according to serostatus and induction immunosuppression. Univariate and multivariate logistic regression was performed. RESULTS: Among 159 heart transplant recipients during the study period, 130 (82%) were eligible for VGC prophylaxis. CMV D/R serostatus was as follows: 24% D+/R-, 30% D+/R+, and 29% D-/R+. 65% and 21% received basiliximab and thymoglobulin induction, respectively, followed by maintenance tacrolimus, mycophenolate mofetil, and prednisone. Twenty-one (16%) recipients suffered CMV infection. There was no association with comorbidities including diabetes mellitus, chronic kidney disease, or mechanical assist devices, nor were there associations with rejection, treatments of rejection, or mortality. When VGC prophylaxis duration was stratified by ≤6 vs ≥12 months, time from heart transplantation to CMV infection was delayed (median 247 vs 452 days, P = .002) but there was no difference in days from VGC discontinuation to onset of CMV infection (median 72 vs 83 days, P = .31). CMV infection occurred most frequently within 6-16 weeks of VGC cessation, and 95% of infections occurred during the 6 months post-prophylaxis period. CONCLUSIONS: Relative to ≤6 months, ≥12 months of VGC did not reduce incidence of CMV infection and only delayed time to onset. 95% of CMV infection occurs within 6 months after cessation of VGC.

Variability in assessing for BK viremia: whole blood is not reliable and plasma is not above reproach - a retrospective analysis.

Polyomavirus nephropathy (PVN) is a major complication of kidney transplantation. Most reports describe polyomavirus viremia either precedes or is detectable at the time of diagnosis of PVN. This association is the basis of current screening recommendations. We retrospectively reviewed the PCR results of blood and urine samples from 29 kidney transplant recipients with biopsy-proven PVN. Biopsies were performed for a rise in serum creatinine or persistent high-level BK viruria. All biopsies showed polyoma virus large T-antigen expression in tubular epithelium using immunohistochemistry. All had viruria preceding or at the time of biopsy (range, 5.2 × 104 to >25 × 106 BKV DNA copies/ml). Twenty (69%) had viremia ranging from 2.5 × 103 to 4.3 × 106 copies/ml at the time of the biopsy. Via blood BK PCR assay, nine (31%) had no BK viremia detected either preceding or at the time of the biopsy. In five recipients where sufficient specimen permitted, additional plasma BK assessment revealed positive detection of viremia. A comparative analysis of assays from two centres was performed with spiked samples. BK DNA may not be detected in the blood of some kidney transplant recipients with histologically confirmed PVN. This may reflect limitation of whole blood as opposed to plasma-based BK DNA assessment.

Optimal strategies for the diagnosis of community-onset diarrhea in solid organ transplant recipients: Less is more.

BACKGROUND: Diarrhea, a common complication after solid organ transplant (SOT), is associated with allograft failure and death. No evidence-based guidelines exist for the evaluation of diarrhea in SOT recipients. We performed a cost analysis to derive a testing algorithm for the diagnosis of community-onset diarrhea that minimizes costs without compromising diagnostic yields. DESIGN: A cost analysis was performed on a retrospective cohort of 422 SOT admissions for community-onset diarrhea over an 18-month period. A stepwise testing model was applied on a population level to assess test costs relative to diagnostic yields. RESULTS: Over an 18-month period, 1564 diagnostic tests were performed and 127 (8.1%) returned positive. Diagnostic testing accounted for $95 625 of hospital costs. The tests with the lowest cost per decrease in the false-omission rate (FOR) were stool Clostridium difficile polymerase chain reaction (PCR) ($156), serum cytomegalovirus quantitative PCR ($1529), stool norovirus (NV) PCR ($4673), and stool culture ($6804). A time-to-event analysis found no significant difference in the length of hospital stay between patients with and without NV testing (P=.520). CONCLUSIONS: A stepwise testing strategy can reduce costs without compromising diagnostic yields. In the first-stage testing, we recommend assessment for C. difficile, cytomegalovirus, and food-borne bacterial pathogens. For persistent diarrheal episodes, second-stage evaluation should include stool NV PCR, Giardia/Cryptosporidium enzyme immunoassay, stool ova and parasite, reductions in immunosuppressive therapy, and possibly endoscopy. Although NV testing had a relatively low cost per FOR, we recommend NV testing during second-stage evaluation, as an NV diagnosis may not lead to changes in clinical management or further reductions in length of hospital stay.

Invasive fungal infection after heart transplantation: A 7-year, single-center experience.

BACKGROUND: Invasive fungal infections (IFIs) are an infrequent but major complication of heart transplantation (HT). We sought to describe the epidemiology at our institution. METHODS: A prospective cohort study of 159 heart transplant recipients was performed from June 2005 to December 2012. IFIs were defined by European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. RESULTS: By univariate analysis, Hispanic ethnicity was associated with IFI (P=.01, odds ratio [OR] 7.0, 95% confidence interval [CI] 1.7-27.9). Subsequently, a multivariate logistic regression was performed adjusting for Hispanic ethnicity, age, and gender. Seventeen IFIs were identified, occurring at a median 110 days post HT (interquartile range: 32-411 days). Five IFIs (29% of IFIs and 3.1% of all HT) occurred during the HT hospitalization, with 13 IFIs during the first year (incidence 8.2%). CONCLUSIONS: The cumulative incidence was 10.7%. IFIs were associated with pre- and post-HT vancomycin-resistant Enterococcus colonization and/or infection, post-HT renal replacement therapy, anti-thymocyte globulin induction, and antibody-mediated rejection. There were no associations with diabetes mellitus, desensitization, 2R/3R cellular rejection, treatments for rejection, re-operation, neutropenia, or cytomegalovirus infection. IFIs were associated with death (P=.02, OR 3.9, 95% CI 1.3-12.1) and 1-year mortality (P<.001, OR 9.0, 95% CI 2.3-35.7), but not 3-year mortality. Associations with Hispanic ethnicity must be validated. Optimal strategies for risk reduction and prophylaxis remain undefined.

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.

Update on donor-derived infections in liver transplantation.

Advances in surgical techniques, immunosuppressive medications, and robust infectious disease prophylaxis have resulted in liver transplantation becoming the treatment of choice for patients with end-stage liver disease and unresectable hepatocellular carcinoma. Nonetheless, organ transplantation is not without risk. Unexpected donor-derived disease transmission is a newly recognized risk that complicates approximately 0.2% of all organ transplants. We review the epidemiology of donor-derived infectious diseases and methods of risk mitigation with a focus on liver transplantation.

Rituximab in combination with chemotherapy versus chemotherapy alone in HIV-associated non-Hodgkin lymphoma: a pooled analysis of 15 prospective studies.

In HIV-positive patients with non-Hodgkin lymphoma (NHL), no benefit of adding rituximab to chemotherapy was seen in a randomized controlled trial (RCT). We performed a meta-analysis of prospective studies to ascertain outcomes in HIV-positive NHL patients treated with chemotherapy (chemo) versus rituximab and chemo (R-chemo). A literature search through September 2011 was performed using the key search "(HIV OR AIDS) AND lymphoma". The main outcomes were overall response rate (ORR), complete response rate (CRR) and 2-year overall survival (OS) and are reported as non-adjusted odds ratio (OR). We identified 15 prospective studies including 1,060 HIV-positive NHL patients, 675 treated with chemo and 385 with R-chemo. There was a higher proportion of HAART in R-chemo patients (82% vs. 68%; p < 0.01) but there were no differences in proportion of patients with advanced stage or high/high-intermediate age-adjusted International Prognostic Index (aaIPI) scores. Meta-analysis showed the OR for ORR, CRR and 2-year OS in patients treated with R-chemo was 1.39 (95% CI 0.79-2.47; p = 0.26), 1.66 (95% CI 0.98-2.82; p = 0.06) and 2.19 (95% CI 1.68-2.86; p < 0.001), respectively. HIV-positive lymphoma patients treated with R-chemo had higher odds for CR and 2-year OS when compared to chemo but also had a higher proportion of HAART usage.

Rectal adenocarcinoma: proposal for a model based on pretreatment prognostic factors.

OBJECTIVE: Currently the choice of chemotherapy regimen in rectal cancer is made prior to surgery in contrast to colon cancer where it is made postoperatively after the pathological stage has been determined. If we could identify which are the important pretreatment prognostic factors in rectal cancer, we could then target those patients with unfavorable features to investigate potentially more effective preoperative chemotherapy regimens aimed at those with unfavorable features. The present study aimed to determine pre-treatment prognostic factors that are associated with an unfavorable outcome. METHODS: A retrospective review of 99 rectal cancer patients operated at the Auxilio Mutuo Hospital, San Juan, Puerto Rico, and the San Pablo Hospital, Bayamón, Puerto Rico was done. Socio-demographic, clinical and treatment data were collected. RESULTS: Of the 99 cases, 54% were males. The mean age +/- standard deviation was 62.2 +/- 10.4. In age-adjusted Cox model, male gender (HR [95%CI]: 3.32 [1.09-10.13]), mucinous carcinoma (HR [95% CI]: 3.67 [1.25-10.77]), and clinical stages II & III (HR [95%CI]: 8.19 [1.08-62.08]) were predictors of poor prognosis. In the multivariate age-adjusted analysis, a tendency towards a poorer prognosis was observed for male patients (HR: 2.60), carcinoembryonic antigen level > or =5 ng/ml (HR: 2.55), mucinous carcinoma (HR: 2.96), and clinical stages II & III (HR: 4.96), although results were not statistically significant (p > 0.05). CONCLUSION: Although current therapeutic results are relatively favorable with preoperative 5-fluorouracil and radiotherapy, future clinical trials should address the management of those cases with adverse pretreatment prognostic factors so that they can be treated with potentially more effective albeit more toxic chemotherapy regimens.

Puerto Rico experience with plugs in the treatment of anal fistulas.

BACKGROUND: Anorectal fistula is a common problem that affects quality of life. Main objective of therapy has been to eradicate the fistula tract while preserving fecal continence. Latest good results for anal fistula treatment have been an anal fistula plug. This study was undertaken to determine if these results could be reproduced in Puerto Rico. METHOD: From January 2003 to January 2008, two experienced colorectal surgeons performed this new operation in 23 consecutive patients. A multivariable analysis was undertaken including age, sex, location of the fistula, previous surgeries, Seton placement before the insertion of the plug, continence pre and post operation, as well as close follow up. No patient with inflammatory bowel disease was included. RESULTS: We had a good result or healing of the fistula in 14 of 23 patients for a success rate of 60%. We had a subgroup of patients who did slightly better and had a healing rate of 66% compared to the 60% of the whole group. It appears to be a trend in favor of the Seton group but is not statically significant. We had 9 failures of 23 patients or 39%. Suppuration was noticed in three patients and all three had failures of the plug with recurrences. CONCLUSIONS: This new operation is another alternative to add to our armamentarium but we need to search for an operation that decreases the incidence of recurrences we had in our study while maintaining function of the sphincters.

Hermansky Pudlak syndrome: an unusual form of procto-colitis.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder consisting of oculocutaneous albinism, platelet dysfunction and systemic complications associated with lipofuscin deposition in the reticuloendothelial system. HPS has been associated with a granulomatous enterocolitis with pathologic features suggestive of Crohn's disease. It remains uncertain if HPS represents a truly distinct form of granulomatous enterocolitis. We report a series of two patients with HPS treated in Puerto Rico, and the results from medical and surgical intervention for gastrointestinal disease. Our experience with HPS patients has shown the difficult management of perineal disease similar in the management of Crohn's. However, complications from the bleeding diathesis necessitate caution during surgery and potential anesthesia complications. Furthermore, avoidance of a perineal wound is preferred, and when possible, ileostomies have fewer complications than colostomies as they do not involve the small bowel.

HIV and Stem Cell Transplantation.

In human immunodeficiency virus (HIV)-infected persons, the incidence of hematologic malignancies, including leukemia and lymphoma, is increased despite the use of successful antiretroviral therapy. Hematopoietic stem cell transplantation (SCT) is emerging as a safe and effective therapy for HIV-infected persons with hematologic malignancies. Management of these patients is complicated by drug-drug interactions involving antiretroviral therapy (ART) that may impact conditioning agent efficacy and metabolism of immunosuppressive medications and potentiate drug toxicities. As such, optimal strategies for ART remain controversial. We discuss recent advances, controversies, and future directions related to SCT in HIV-infected persons, including the investigation of allogeneic SCT as a strategy for HIV cure.

EFV/FTC/TDF-associated hepatotoxicity: a case report and review.

The fixed-dose combination efavirenz, emtricitabine, and tenofovir (EFV/FTC/TDF) is a first-line agent for the treatment of HIV. We report the case of a 40-year-old female with a history of HIV acquired through heterosexual contact who initiated EFV/FTC/TDF. Hepatitis B and C serologies were negative, CD4 cell count was 253 cells per cubic millimeter (15.8%), and HIV viral load was 67,373 copies per milliliter. Eight months later she developed transaminitis and severe right upper quadrant pain. Neither illicit drug abuse nor hepatotoxic medication such as acetaminophen was reported. After evaluation including negative acute viral hepatitis studies, EFV/FTC/TDF was discontinued; both her transaminitis and pain resolved. Hepatotoxicity is most often associated with efavirenz. Rarely, fulminant hepatic failure occurs. Efavirenz-related hepatotoxicity is thought to result from a cellular self-digestion process known as autophagy. This is the first report to our knowledge of EFV/FTC/TDF-related hepatotoxicity.

Clinical characteristics and outcomes in hospitalized patients with respiratory viral co-infection during the 2009 H1N1 influenza pandemic.

BACKGROUND: The clinical consequences of co-infection with two or more respiratory viruses are poorly understood. We sought to determine if co-infection with pandemic 2009-2010 influenza A H1N1 (pH1N1) and another respiratory virus was associated with worse clinical outcomes. METHODS: A retrospective cohort study was performed of all hospitalized patients with a positive respiratory viral panel (RVP) for two or more viruses within 72 hours of admission at our institution from October 2009 to December 2009. We compared patients infected with one respiratory virus to those with respiratory viral co-infection. RESULTS: We identified 617 inpatients with a positive RVP sample with a single virus and 49 inpatients with a positive RVP sample for two viruses (i.e. co-infection). Co-infected patients were significantly younger, more often had fever/chills, tachypnea, and they more often demonstrated interstitial opacities suggestive of viral pneumonia on the presenting chest radiograph (OR 7.5, 95% CI 3.4-16.5). The likelihood of death, length of stay, and requirement for intensive care unit level of care were similar in both groups, but patients with any respiratory virus co-infection were more likely to experience complications, particularly treatment for a secondary bacterial pneumonia (OR 6.8, 95% CI 3.3-14.2). Patients co-infected with pH1N1 and another respiratory virus were more likely to present with chest radiograph changes suggestive of a viral pneumonia, compared to mono-infection with pH1N1 (OR 16.9, 95% CI 4.5-62.7). By logistic regression using mono-infection with non-PH1N1 viruses as the reference group, co-infection with pH1N1 was the strongest independent predictor of treatment for a secondary bacterial pneumonia (OR 17.8, 95% CI 6.7-47.1). CONCLUSION: Patients with viral co-infection, particularly with pH1N1, were more likely to have chest radiograph features compatible with a viral pneumonia and complications during their hospital course, particularly treatment for secondary bacterial pneumonia. Despite this, co-infection was not associated with ICU admission.