Non-transplant Patient Research Articles

P.051: Comparision of invasive pulmoner aspergillosis between transplant and non-transplant patient.

P.051: Comparision of invasive pulmoner aspergillosis between transplant and non-transplant patient.

Case report: a special case of cryptococcal infection-related inflammatory syndrome in a non-HIV infected and non-transplant patient

BackgroundCryptococcal meningoencephalitis (CM) is a severe infection of central nervous system with high mortality and morbidity. Infection-related inflammatory syndrome is a rare complication of CM. Herein, we report a case of CM complicated by infection-related inflammatory syndrome.Case presentationA 42-year-old man with chronic hepatitis B presented with a 3-day history of aphasia and left hemiparesis at an outside medical facility. The brain magnetic resonance imaging (MRI) showed symmetric and confluent hyperintense signal abnormalities mainly located in the basal ganglia, internal capsule, external capsule, periventricular, corona radiata, frontal and temporal lobes. Cerebrospinal fluid (CSF) examinations revealed elevated leukocyte and protein. India ink staining was positive for Cryptococcus. CSF culture and metagenomic next-generation sequencing (mNGS) confirmed Cryptococcus neoformans. Initial response was observed with intravenous fluconazole (400 mg per day). However, 11 days later, he developed impaired consciousness and incontinence of urine and feces. A repeat brain MRI showed the lesions were progressive and enlarged. The patient was referred to our department at this point of time. Repeat CSF analysis (India ink staining, culture and mNGS) re-confirmed Cryptococcus. However, clinical worsening after initial improvement, laboratory examinations and brain MRI findings suggested a diagnosis of infection-related inflammatory syndrome. Therefore, a combination of corticosteroids and antifungal therapy was initiated. At follow-up, a complete neurological recovery without any relapse was documented. The repeat brain MRI showed complete resolution of the previous lesions.ConclusionsThis case demonstrated that cryptococcal inflammatory syndromes must be suspected in cases of CM if an otherwise unexplained clinical deterioration is observed after initial recovery. The same can happen even before the primary infection is controlled. Thus, timely identification and prompt treatment is vital to reduce the mortality and disability of CM. The administration of corticosteroids in combination with antifungal therapy is an effective strategy in such cases.Graphical abstractClinical course and treatment process of the patient. Hemiparalysis and aphasia improved after the initiation of antifungal treatment. However, the patient developed impaired consciousness companied by deterioration of brain MRI findings. He was treated with adjunctive glucocorticoid taper therapy consisting of dexamethasone (20 mg/day, intravenously) for 1 week followed by oral prednisone 1 mg/kg/day, tapered based on clinical and radiological response, along with amphotericin B (0.6 mg/kg/day, intravenously), voriconazole (400 mg/day in 2 divided doses, intravenously), and 5-flucytosine (100 mg/kg/day in 4 divided doses, orally). Two weeks later, his symptoms improved significantly. After discharge, he began oral voriconazole for consolidation and maintenance therapy for 8 weeks and 9 months respectively. He recovered without any neurological sequelae at 6-month follow-up. Note: MRI = magnetic resonance imaging.

Autologous stem cell transplantation in multiple myeloma patients over 70 years: A GIMEMA Lazio Working Group experience in a retrospective case-control study.

High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is the standard treatment for young patient ≤65 years with multiple myeloma (MM). The role of auto-SCT in elderly patients older than 70 years remains controversial in the era of novel agents and especially since the recent introduction of monoclonal antibodies (AbMo). In this study, we evaluated 12 patients with MM over 70 years old undergoing auto-SCT (elderly graft cohort) in seven centers of GIMEMA Working Group Lazio. We compared the baseline characteristics, treatment and outcome with 97 MM elderly patients who did not receive auto-SCT (nontransplant patients) from the same registry who were ≥ 70 years old, but did not undergo auto-SCT. The median progression free survival (PFS) for graft versus no-graft cohort was 56.4 versus 26.1months, respectively. There was a trend for better PFS among graft compared to nontransplant patient (p=.1). On the other hand, the median overall survival for transplant versus nontransplant cohort was 107.6 versus 49.5months (p=.02). Despite the small number of patients aged ≥70 years and ≤74 years, it seems that auto-SCT is well tolerated, safe and effective. Therefore, we propose that it should be considered an important treatment option in the era of new drugs in elderly fit patients with MM.

CMV-colitis in a pediatric non-transplant ALL patient receiving chemotherapy; A case report

Cytomegalovirus (CMV) is the leading cause of viral-associated congenital infections. Moreover, it can also be acquired. Between 50 to 80 percent of the world’s population is seropositive for CMV and most clinical disease occurs in individuals previously infected with CMV. Rarely, serious CMV infection has occurred in individuals with healthy immune system. In contrast to immunocompetent patients, higher morbidity and mortality of CMV end organ disease is considered in immunocompromised patients. According to available evidence, gastrointestinal (GI) disease has lower prevalence in case of CMV-induced organ involvement, especially in pediatric non-transplant acute leukemia. In this report, we present a 12-year-old girl, known case of acute lymphoblastic leukemia (ALL) receiving maintenance chemotherapy with manifestations of gastroenteritis and significant weight loss. Initial laboratory data, demonstrated mild pancytopenia especially lymphopenia and thrombocytopenia. After excluding more common etiologies, colonoscopy with multiple biopsies were taken which was indicative of CMV-colitis. Intravenous (IV) ganciclovir for 3 weeks and oral valganciclovir for about 9 months were initiated. Follow-up courses for CMV surveillance included blood qualitative CMV polymerase chain reaction (PCR) and colonoscopy with biopsy which were negative for CMV but tissue qualitative CMV PCR was positive for CMV in about 7 months after initiation of treatment. Oral treatment was decided to be continued. To sum up, plenty of guidelines have been developed in stem cell transplantation and human immunodeficiency virus (HIV) patients but non-transplant leukemic setting, is a neglected area in the field of CMV infection management.

Plasma Neutrophil Gelatinase-Associated Lipocalin to Predict Acute Kidney Injury After Lung Transplantation: A Multicenter Cohort Study

<h3>Purpose</h3> Post-operative acute kidney injury (AKI) occurs in up to 65% of lung transplant recipients and is associated with chronic kidney disease and mortality. Plasma neutrophil gelatinase-associated lipocalin (pNGAL) is a biomarker of early structural kidney damage that has improved prediction of AKI compared with clinical variables alone in non-transplant patient populations. We sought to determine the association of pNGAL with AKI after lung transplantation and whether it could improve AKI prediction. <h3>Methods</h3> We included 189 lung transplant recipients enrolled in the prospective 5-center Lung Transplant Outcomes Group Acute Kidney Injury (LTOG-AKI) cohort study from 7/2017 - 6/2019. We tested pNGAL levels pre-transplant and at 6 and 24 hours post-reperfusion. We defined AKI using Kidney Disease Improving Global Outcomes creatinine criteria during the first 7 post-op days. We tested associations of pNGAL and clinical variables with AKI using the Wilcoxon rank-sum test. We constructed logistic regression models to predict AKI using pNGAL alone, clinical variables alone, and pNGAL plus clinical variables. <h3>Results</h3> AKI developed in 95 (50%) patients (45 (24%) stage 1, 21 (11%) stage 2, 29 (15%) stage 3), occurring a median of 2 (IQR 1-3) days post-op. pNGAL levels at 6h (p=0.001) and 24h (p<0.001) were significantly associated with AKI. Over 90% of 6h pNGAL levels were >150 ng/ml, the cut-off typically used to denote high risk of AKI in non-transplant populations. A model including clinical variables of recipient age and gender, transplant diagnosis and type, and lung allocation score had an area under the receiver operating characteristics (auROC) curve higher than pNGAL alone (Figure 1). Adding pNGAL to the clinical model did not improve the auROC curve. Model results were similar when defining AKI as stage 2-3 only. <h3>Conclusion</h3> Early post-lung transplant pNGAL levels were associated with AKI but did not add to clinical variables in predicting AKI.

Is COVID-19 infection more severe in kidney transplant recipients?

There are no studies which have compared the risk of severe COVID‐19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID‐19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single‐center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID‐19 or mortality. Severe COVID‐19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30‐day cumulative incidence of severe COVID‐19 did not differ between KTR and nontransplant patients; however, 30‐day COVID‐19‐related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C‐reactive protein (CRP) were associated with severe COVID‐19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID‐19‐related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID‐19‐related mortality compared to nontransplant hospitalized patients.

Development of Phenotyping Algorithms for the Identification of Organ Transplant Recipients: Cohort Study.

BackgroundStudies involving organ transplant recipients (OTRs) are often limited to the variables collected in the national Scientific Registry of Transplant Recipients database. Electronic health records contain additional variables that can augment this data source if OTRs can be identified accurately.ObjectiveThe aim of this study was to develop phenotyping algorithms to identify OTRs from electronic health records.MethodsWe used Vanderbilt’s deidentified version of its electronic health record database, which contains nearly 3 million subjects, to develop algorithms to identify OTRs. We identified all 19,817 individuals with at least one International Classification of Diseases (ICD) or Current Procedural Terminology (CPT) code for organ transplantation. We performed a chart review on 1350 randomly selected individuals to determine the transplant status. We constructed machine learning models to calculate positive predictive values and sensitivity for combinations of codes by using classification and regression trees, random forest, and extreme gradient boosting algorithms.ResultsOf the 1350 reviewed patient charts, 827 were organ transplant recipients while 511 had no record of a transplant, and 12 were equivocal. Most patients with only 1 or 2 transplant codes did not have a transplant. The most common reasons for being labeled a nontransplant patient were the lack of data (229/511, 44.8%) or the patient being evaluated for an organ transplant (174/511, 34.1%). All 3 machine learning algorithms identified OTRs with overall >90% positive predictive value and >88% sensitivity.ConclusionsElectronic health records linked to biobanks are increasingly used to conduct large-scale studies but have not been well-utilized in organ transplantation research. We present rigorously evaluated methods for phenotyping OTRs from electronic health records that will enable the use of the full spectrum of clinical data in transplant research. Using several different machine learning algorithms, we were able to identify transplant cases with high accuracy by using only ICD and CPT codes.

Hypertension in cardiac transplant recipients: tackling a new face of an old foe.

Systemic hypertension (HTN) is a common complication arising in the heart transplant recipient. This article aims to review the most current literature and update readers on the epidemiology, pathophysiology and management of HTN in heart transplant patients. In contrast to the general nontransplant hypertensive patient population, traditional risk factors, including family history of HTN, obesity and diabetes, play a minor role in the genesis of posttransplant HTN. Dysregulation in sodium and water balance, vascular stiffness, endothelial dysfunction, abnormal cardiorenal neural reflexes resulting from immunosuppression and cardiac denervation seem to be the predominant factors leading to postheart transplant HTN. Calcineurin inhibitors induced nephrotoxicity and steroid use further contributes to posttransplant HTN. Owing to the paucity of data, particularly randomized controlled trials to guide the evaluation and management of HTN in the cardiac transplant patients, much of the available data come from the renal transplant population. The choice of antihypertensive should be based on timing related to transplantation and patient's comorbidities. Although calcium channel blockers and loop diuretics are the preferred agents in the early postheart transplant period, angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers may be beneficial in the late postheart transplant period especially in the setting of diabetes and in the presence of proteinuria.

Morbidity and mortality after general surgery in heart and lung transplant patients

BackgroundHeart and lung transplant patients can develop conditions necessitating general surgery procedures. Their postoperative morbidity and mortality remain poorly characterized and limited to case series from select centers. MethodsThe National Inpatient Sample (1998–2015) was used to identify 6433 heart and 3015 lung transplant patient admissions for general surgery procedures. For a comparator group, we identified 23,764,164 nontransplant patient admissions for the same procedures. Patient morbidity and mortality after general surgery were compared between transplant patients and nontransplant patients. Data were analyzed with frequency tables, χ2 analysis, and a mixed-effects multivariate regression. ResultsOverall mortality was higher and length of stay longer in the transplant group compared to the nontransplant group. Analysis revealed that hospital size and comorbidities were predictors of mortality for patients undergoing certain general surgery procedures. Transplant status alone did not predict mortality. ConclusionOur findings demonstrate that heart and lung transplant patients, compared to nontransplant patients, have more complications and a higher length of stay after certain general surgery procedures.

An Unusual Cause of Recurrent Pleural Effusion

Abstract Cryptococcus neoformans is a yeast that can cause severe infection in the immunocompromised. It is commonly associated with meningitis in patients with underlying HIV infection; however, infections can occur in other immunosuppressed hosts as well as the immunocompetent. Pulmonary disease is well described, but recurrent pleural effusion and empyema are rare. We describe a case in a non–HIV-infected, nontransplant cirrhotic patient presenting with recurrent pleural effusions and cryptococcal empyema. The patient is a 66-year-old man with cirrhosis, diabetes, and kidney disease who presented with 3 months of dyspnea complicated by recurrent pleural effusion and low protein ascites after treatment of hepatitis C virus. Routine cultures from multiple thoracenteses were unrevealing. Fungal culture ultimately grew C. neoformans/gattii. His serum cryptococcal antigen titer was 1:40, and chest imaging revealed several pulmonary nodules. He was admitted for evaluation of disseminated disease and central nervous system involvement, which was unremarkable. He was started on oral fluconazole 200 mg daily dosed for his renal function and was doing well in outpatient follow-up. Patients with cirrhosis tend to have a higher incidence of cryptococcal disease and are more likely to have disseminated infection with higher mortality. It is possible that deficiencies in complement and cytokine levels as well as leukocyte function may contribute to this increased risk. Effusions are an uncommon manifestation of pulmonary cryptococcosis and, as with the case in our patient, may resemble hepatic hydrothorax, leading to a delay in antifungal therapy. In conclusion, patients with liver disease have an increased risk of cryptococcosis. A high index of suspicion must be maintained for infection and should be considered in patients with recurrent effusions.

Clinical presentations of Hepatitis E: A clinical review with representative case histories

SummaryHepatitis E virus (HEV) typically causes an acute, self-limiting hepatitis and is among the commonest cause of such presentations. Hepatitis E viral infection is also increasingly recognized as a cause of chronic hepatitis amongst the immunocompromised, particularly amongst solid organ transplant recipients. Chronic HEV infection remains an underdiagnosed disease and chronic infection can lead to rapidly progressive liver fibrosis and cirrhosis. This review examines current understanding of the HEV. We illustrate typical clinical presentations, management strategies [(based upon guidelines from both the British Transplant Society (BTS) and European Association for the study of liver (EASL)] and outcomes of HEV infection in different cohorts of patients by highlighting select transplant and non-transplant patient cases, from one of the largest tertiary Hepatology centres in Europe.

1134. Novel T2Candida Panel Assay Compared With Blood Cultures for Detection of Candidemia in Transplant and Non-Transplant Patients

BackgroundBlood culture (BC) the current “gold” standard for detection of candidemia has a sensitivity of ~50% and turnaround time (TAT) of 2–5 days. T2Candida Panel (T2) a magnetic resonance nano-diagnostic test done directly on blood samples detects C. albicans/C. tropicalis, C. krusei/C. glabrata, and C. parapsilosis. Clinical trials of T2 showed good sensitivity, specificity, NPV 99% and TAT of 3–5 hours. The performance of T2 in high-risk transplant (Tx) population is unknown. T2 was implemented at our institution in October 2015. We evaluated the performance characteristics of T2 and BC in our Tx and non-transplant (non-Tx) patient populations.MethodsThis was an observational, retrospective, cross-sectional evaluation of patients with suspected candidemia that had T2 done from October 2015 to October 2017 at a multihospital healthcare system in Detroit, MI. Performance characteristics of the T2 and BC in Tx and non-Tx patients were compared. BC obtained within 7 days before or after the T2 test were included in the analysis. TAT, sensitivity, specificity, PPV and NPV were calculated using positive BC as the standard. Differences between groups were assessed using two sample proportions testing at α = 0.05.ResultsA total of 1,272 patients with suspected candidemia had T2 done: 1,162 (91%) non-Tx and 110 (9%) Tx patients. Average TAT for T2 was 13 hours (5–41) vs. 34 hours (21–109) to initial positive BC result and 4 days (3–13) to species-specific BC result. In four non-Tx patients with negative T2, C. lusitaniae, C. dubliniensis, and C. kefyr were isolated in BC. Performance characteristics of T2 and BC in the two groups is shown (Table 1). Of the T2+/BC− cases (n = 102), 9% had retinitis and 9% had invasive candidiasis.ConclusionThe rapid TAT, good sensitivity, and high NPV of T2 in Tx patients has clinical implications and can help support antifungal stewardship efforts in this population. The clinical significance of T2 positivity in the presence of negative BC needs further investigation.Table1: Performance Characteristics of T2 Compared with BC (N = 1,272)Tx (n = 110)Non-Tx (n = 1162) P-valueT2 + and blood culture +5 (4.5%)35 (3.01%)0.3917T2 + and blood culture −19 (17.3%)86 (7.4%)0.0003T2 - and blood culture +1 (0.9%)41 (3.5%)0.1431Sensitivity83.3%46.1%Specificity81.9%92.4%PPV20.8%28.9%NPV98.8%96.2%Disclosures G. Alangaden, T2 Biosystems: Speaker’s Bureau, Educational grant and Speaker honorarium.

Case report: a fatal case of disseminated adenovirus infection in a non-transplant adult haematology patient

BackgroundWe report a fatal case of disseminated adenovirus infection in a non-transplant haematology adult patient with chronic lymphocytic leukaemia who had completed combination chemoimmunotherapy a few months before developing respiratory symptoms. In such non-transplant patients, monitoring for adenovirus in the blood is not routine. However, with adenoviruses, when there is a more peripheral (i.e. non-blood) site of infection such as the chest, serial adenovirus monitoring in blood for the duration of that illness may be warranted.Case presentationThis case started with an initial bacterial chest infection that responded to treatment, followed by an adenovirus pneumonitis that disseminated to his blood a week later with levels of up to 92 million adenovirus DNA copies/ml. Despite prompt treatment with cidofovir, his respiratory function continued to deteriorate over the next two weeks and he was moved to intensive care. Intravenous immunoglobulin and ribavirin were subsequently added to his treatment. However, he died soon after this with a final adenovirus load of 20 million copies/ml in his blood.ConclusionsWe recommend that even in non-transplant haematology patients, where such patients present with an acute respiratory adenovirus infection, teams should consider checking the blood for adenovirus to check for signs of disseminated infection. The earlier this can be tested, the earlier treatment can be initiated (if adenovirus positive), which may produce more successful clinical outcomes.

OR52 AT1R antibody in pediatric heart transplant patients: What are we really detecting

Aim The frequency and impact of AT1R antibodies in pediatric heart transplantation has not been well studied. Our aim was to measure AT1R antibodies (AT1R-Ab) in this patient population and pediatric controls and to assess for non-specific reactivity in this assay. Methods We included 42 patients ( n = 154 samples) for whom pre- and post-transplant sera and HLA Ab data were available. AT1R-Ab were measured by ELISA (One Lambda Inc.). Samples were tested/interpreted as per product insert. Age-matched, sex-balanced, non-transplant patient controls ( n = 27) were collected from cardiac–catheterization laboratory. A subset with positive results ( n = 52 sera from 20 patients) was re-tested following Adsorb Out (One Lambda Inc.). Analysis was performed using GraphPad. Results No significant difference was observed between patient and control AT1R antibody levels (Fig. 1). Values over 40 U/ml were detected in 38% of patient sera. Adsorbed sera had significantly decreased AT1R values vs non-adsorbed sera (Fig. 2A). There was no significant change in AT1R-Ab from pre- to post-transplant overall in either group but a higher proportion of patients changed from positive to negative using adsorbed vs non-adsorbed sera (20% vs 12.5%) (Fig. 2B and C). Conclusions A high proportion of patients and controls were positive for AT1R-Ab, however, many sera appear to be false positive, possibly due to BSA reactivity or incomplete blocking in the assay. As more assays for non-HLA Ab are added into our clinical algorithms, appropriate controls must be included. A ‘blank’ well would be useful in this assay for accurate interpretation of results. Association of the adsorbed and non-adsorbed AT1R-Ab to transplant outcomes is currently being assessed.

Disease Reversibility in Patients With Post-Hepatitis C Cirrhosis: Is the Point of No Return the Same Before and After Liver Transplantation? A Review.

Liver fibrosis can regress in patients with chronic hepatitis in whom the underlying cause of liver damage is adequately treated. Studies documenting this benefit have been mostly performed in the setting of viral hepatitis, particularly hepatitis C virus, where sustained viral response has been unequivocally shown to result in histological and clinical improvement. With the advent of the new IFN-free regimens, highly effective and safe even in those historically considered "difficult to treat and cure patients," additional benefits have been documented in patients treated at advanced stages of disease, including improvement in liver function with hepatic "recompensation," reduction of portal hypertension, and eventually avoidance of liver transplantation. Disease reversibility has been also demonstrated in the posttransplant setting and appears to be similar to what is observed in the nontransplant patient.

Chronic Hepatitis E in a Case of Chronic Lymphocytic Leukemia: A Rare Presentation of Chronic HEV in a Non-transplant Patient

A 72-year-old French man with chronic lymphocytic leukemia (CLL) evaluated for continued unexplained jaundice, elevated transaminases, and fatigue for five months. His initial labs were remarkable for elevated transaminases [AST 134 U/L, ALT 216 U/L] and mild hyperbilirubinemia [1.4 mg/dL]. A liver biopsy revealed chronic hepatitis with mild portal fibrosis, focal mild periportal fibrosis, and steatosis. The pattern of lymphocytic staining was not compatible with CLL, and immunochemistry was negative for CLL. There were no intracytoplasmic inclusions, negative for alpha 1 AT deficiency, no Mallory bodies, and negative for Prussian blue stain. His past medical history was most significant for CLL first diagnosed 10 years prior to the initial hepatology visit. Rituxan based chemotherapy was started 4 years ago. Medical history is also notable for coronary artery disease s/p PCI with stents at age 68. He had an appendectomy during childhood and a cholecystectomy at 67 years old. He consumes one glass of wine every other day and has a former 50 pack year smoking history. He endorsed occasional consumption of undercooked pork and beef tartare every couple months, which is a delicacy in his home in Marseilles, France. His last visit to Southwestern France was 6 years ago, and his last foreign travel was on a cruise trip to Central America 1 years ago. There was no clinically apparent hepatomegaly or splenomegaly. An initial laboratory work-up was unrevealing, including hepatitis A, B and C serologies & viral count, ASMA, AMA, ANA, ferritin, and ceruloplasmin. However, Hepatitis E Ab Ig M was detected positive on the initial hepatology clinic visit. The test was repeated and positive again one month later. Samples sent for HEV RNA detection at the CDC lab was positive. The patient was confirmed to have Chronic Hepatitis E and started on ribavirin 600mg twice daily for 3 months. Previously known as a self-limiting acute infection, hepatitis E virus (HEV) has been found to cause chronic hepatitis, particularly in post organ transplant patients from Southwestern France on immunosuppressive therapy and especially in those consuming undercooked pork. While awareness of chronic Hepatitis E is growing, it is not commonly reported outside of post-transplant recipients. Chronic hepatitis E should be considered in the differential for all immunosuppressed patients with similar epidemiological risk factors and unexplained chronic hepatocellular disease.

Disseminated Cryptococcal Disease in Non-HIV, Nontransplant Patient.

Disseminated cryptococcal infection carries a high risk of morbidity and mortality. Typical patients include HIV individuals with advanced immunosuppression or solid organ or hematopoietic transplant recipients. We report a case of disseminated cryptococcal disease in a 72-year-old male who was immunocompromised with chronic lymphocytic leukemia and ongoing chemotherapy. The patient presented with a subacute history of constitutional symptoms and headache after he received five cycles of FCR chemotherapy (fludarabine/cyclophosphamide/rituximab). Diagnosis of disseminated cryptococcal disease was made based on fungemia in peripheral blood cultures with subsequent involvement of the brain, lungs, and eyes. Treatment was started with liposomal amphotericin, flucytosine, and fluconazole as induction. He was discharged after 4 weeks of hospitalization on high dose fluconazole for consolidation for 2 months, followed by maintenance therapy.

Intracellular ATP Production in CD4+ T Cells as a Predictor for Infection and Allograft Rejection in Trough-Level Guided Pediatric Liver Transplant Recipients Under Calcineurin-Inhibitor Therapy

The assessment of cell-mediated immune responses through the measurement of intracellular adenosine-tri-phosphate (iATP) production (Cylex ImmuKnow) as a pharmacodynamic biomarker of immune function represents a potential tool to optimize individual immunosuppressive therapy independent of drug dosage or trough levels. This study aims to investigate the correlations between iATP and adverse events, immunosuppression, calcineurin-inhibitor-trough levels, and age. In this prospective trial, 31 nontransplant pediatric subjects and 50 consecutive children were included after they underwent liver transplantation (LTX). During the study period, 4 allograft rejections and 3 acute infections occurred. The patients were treated with cyclosporine, tacrolimus, mycophenolate mofetil, and everolimus either as monotherapy or in combinations. The reactivity of the immune system was measured as iATP concentration in CD4+ T-cells after in vitro stimulation by phytohemagglutinin. The iATP concentrations in patients with intercurrent, clinically significant infections were in the low immune response range (median iATP 181 versus 251 ng/mL, P = 0.308), whereas the patients with incidental allograft rejection had significantly higher iATP concentrations as compared with the event-free group (median iATP 444 versus 251 ng/mL, P = 0.017). However, there was a wide range of iATP concentrations in both nontransplant and LTX patient groups, and no clear iATP cut-off values for an increased risk of infection or rejection could be defined. Post LTX, stable-phase patients showed a significantly lower iATP compared with respective controls (median iATP 297 versus 384 ng/mL, P = 0.013). No significant correlation between calcineurin-inhibitor-trough concentrations and iATP was found. iATP was not correlated with age, but was inversely correlated with time after transplantation. The observed correlation between clinical events and iATP concentrations is similar to the findings previously reported in adult patients who underwent transplantation. The lack of correlation of iATP with trough drug concentrations suggests that the ImmuKnow assay provides independent information that may be useful to guide immunosuppressive therapy in pediatric (liver) transplant patients. However, the wide range of iATP levels in event-free patients suggests that serial iATP measurements will be necessary to assess and guide the individual immunosuppressive therapy. Further investigations are needed to evaluate and extend these findings.

Management of Hypertension in Renal Transplant Patients: A Comprehensive Review of Nonpharmacologic and Pharmacologic Treatment Strategies

To review the guidelines and literature for the treatment of hypertension in renal transplant patients and to provide guidance to practitioners in the selection of appropriate nonpharmacologic and pharmacologic treatment options. A PubMed search (January 1948-March 2010) was performed using the search terms hypertension, antihypertensive agents, blood pressure, and cardiovascular disease, in combination with renal transplant and kidney transplant. The search was limited to articles published in English. All relevant peer-reviewed original studies, meta-analyses, guidelines, consensus statements, and review articles were examined. In addition, reference citations from publications identified were reviewed. All literature found was evaluated for inclusion. Review articles as well as prospective and retrospective original research articles were reviewed. Hypertension after solid organ transplantation is a problem commonly encountered in patients during their posttransplantation clinic visits. Effective management of these patients' hypertension is crucial, as hypertension left untreated may lead to increased morbidity and mortality as well as graft loss. The unique, multifactorial etiology of hypertension in this population makes treatment choices more challenging compared to treatment of a nontransplant patient. Therefore, to guide practitioners in this process, we developed a hypertension management protocol, taking into account the unique considerations faced in the adult renal transplant population. The review guides practitioners from the initial assessment of patients' hypertension through the evaluation and selection of nonpharmacologic and pharmacologic treatment options and provides information about the discontinuation of certain antihypertensive medications. It also provides a concise, but comprehensive review of the major antihypertensive drug classes and economic considerations. The management of hypertension in posttransplantation patients is challenging and complicated, yet necessary to prevent morbidity, mortality, and graft loss for these patients. Therapy should be individualized based on patient assessment, response to previous therapy, and economic considerations.

Imaging findings of biliary cast syndrome in a non-transplant patient

患者女,60岁,受凉后畏寒、发热伴咳嗽、咳白痰3 d于2009年2月14日入院.1个月前曾患急性胰腺炎,既往有糖尿病、肾功能不全、胆囊及胆管结石、胆囊炎、胆管炎病史.体检:体温40℃,皮肤巩膜中度黄染,腹肌紧张,无压痛及反跳痛.实验室检查提示肝功能异常、梗阻性黄疸,血淀粉酶正常。