Unilateral cortical FLAIR-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures (FLAMES): characterization of a distinct clinico-radiographic syndrome.

OBJECTIVE: To characterize the clinical symptoms and magnetic resonance imaging (MRI) findings of unilateral cortical FLAIR-hyperintense Lesions in Anti-MOG-associated Encephalitis with Seizures (FLAMES). METHODS: This is a case report and systematic review of the literature to identify cases of unilateral cortical FLAMES. Cases were reviewed to determine the frequency of clinical symptoms (seizures, headache, fever and cortical symptoms referable to FLAMES location), and to determine whether MRI abnormalities are restricted to the unilateral cortex in this syndrome. RESULTS: We identified 20 cases of unilateral cortical FLAMES for review. Among them, 17/20 (85%) had seizures, 14/20 (70%) had headache, 13/20 (65%) had fever, 11/20 (55%) reported cortical symptoms referable to the FLAMES location, and 19/20 (95%) reported at least two of these four findings. On MRI 4/20 (20%) had some contralateral hemispheric cortical signal abnormality, and 6/20 (30%) had MRI findings concerning for meningeal inflammation. CONCLUSIONS: In patients with unilateral cortical FLAMES, the clinical symptoms of seizures, headache, fever and cortical symptoms referable to the FLAMES location are frequent. Although initially described as a unilateral cortical encephalitis, bilateral cortical involvement and possible meningeal inflammation could indicate a broader disease spectrum. Recognition of this distinct clinico-radiographic syndrome may facilitate prompt diagnosis and treatment.

High-dose corticosteroids for acute cytomegalovirus-associated transverse myelitis in the immunocompetent patient: a case report and systematic review.

We present an immunocompetent patient with transverse myelitis (TM) during acute cytomegalovirus (CMV) infection, as evidenced by a reactive serum CMV IgM and CMV viremia. The patient had an excellent outcome after receiving only high-dose methylprednisolone. Given concerns that practitioners may have around the use of immunosuppressive therapy for this potentially infectious myelopathy, we systematically reviewed the literature to assess outcomes after administration of high-dose corticosteroids to this population. Despite severe disease at clinical nadir with inability to ambulate, immunocompetent patients with acute CMV-associated TM who received high-dose corticosteroids had good clinical outcomes 1 month to 1 year after presentation.

A Multicenter Case-control Study of the Effect of Acute Rejection and Cytomegalovirus Infection on Pneumocystis Pneumonia in Solid Organ Transplant Recipients.

BACKGROUND: Pneumocystis pneumonia (PCP) is associated with morbidity and mortality in solid organ transplant (SOT) recipients. In this case-control study, we determined the association between posttransplant PCP and 3 variables: cytomegalovirus (CMV) infection, allograft rejection, and prophylaxis. METHODS: Eight transplant centers participated. For each case (SOT recipient with PCP), 3-5 controls (SOT recipients without PCP) were included. Controls were matched to the cases based on transplant center, type of allograft, and date of transplantation (±6 months). RESULTS: We enrolled 53 cases and 209 controls. Transplant types included kidney (n = 198), heart (n = 30), liver (n = 15), kidney-pancreas (n = 14), and lung (n = 5). PCP occurred beyond 12 months after transplantation in 43 (81.1%) cases. Thirty-four cases (64.1%) required admission to the intensive care unit, and 28 (52.8%) had mechanical ventilation. Allograft failure occurred in 20 (37.7%) cases, and 14 (26.9%) died. No patient developed PCP prophylaxis breakthrough. The proportion of female sex (P = .009), kidney dysfunction (P = .001), cardiac diseases (P = .005), diabetes mellitus (P = .03), allograft rejection (P = .001), CMV infection (P = .001), and severe lymphopenia (P = .001) were significantly higher in cases. In the logistic regression model, CMV infection (adjusted odds ratio [aOR], 4.6 [95% confidence interval {CI}, 2.0-10.5]) and allograft rejection (aOR, 3.0 [95% CI, 1.5-6.1]) significantly increased the likelihood of PCP. CONCLUSIONS: PCP was mostly a late-onset disease occurring after complete course of prophylaxis, particularly among patients with CMV infection or allograft rejection. PCP is associated with significant allograft loss. Extended prophylaxis targeting recipients with allograft rejection or CMV infection may reduce the risk of PCP.

Primary Epstein-Barr virus infection, seroconversion, and post-transplant lymphoproliferative disorder in seronegative renal allograft recipients: a prospective cohort study.

BACKGROUND: Epstein-Barr virus (EBV)-seronegative renal transplant recipients are at risk of post-transplant lymphoproliferative disorder (PTLD). We compared primary EBV infection, seroconversion, and PTLD in EBV-seronegative patients who received renal allograft from seropositive or seronegative donors (D+/R- and D-/R-, respectively). METHODS: We prospectively followed 25 D+/R- and 8 D-/R- recipients. We followed patients from January 1999 to June 2009 with clinical visits, monthly EBV polymerase chain reaction tests, and serologic tests for a period of 1 year after kidney transplantation and on an individual basis thereafter. RESULTS: Three patients (9%) developed PTLD including 2 early-onset (<12 months) and 1 late-onset (>12 months) disease. In D+/R- and D-/R- patients, the frequencies of PTLD (8% vs. 12.5%, P = 0.7), EBV seroconversion (64% vs. 50%, P = 0.4), and EBV viremia (40% vs. 25%, P = 0.6) were not significantly different. Clinical, serologic, and virologic surveillance as well as reduction in immunosuppression after evidence of primary EBV infection resulted in a PTLD rate of 9%, despite a seroconversion rate of 60.6%. Rate of graft loss after reduction in immunosuppression was 10% (2 of 20), which was not significantly different from 13 patients without EBV seroconversion (no graft loss, P = 0.5). Rates of viremia, seroconversion, and PTLD in D+/R- and D-/R- patients appear to be similar. CONCLUSIONS: The incidence of PTLD in renal transplants ranges from 0.5% to 2.9%. Our data show a significantly higher rate in EBV-seronegative renal allograft recipients, suggesting the need for close surveillance. Our data also suggest that donors for EBV-seronegative recipients may be accepted irrespective of positive or negative serostatus, with ongoing surveillance important in either circumstance.

Mold infections in lung transplant recipients.

Fungal infections continue to produce morbidity and mortality in lung transplant recipients despite the widespread use of antifungal prophylaxis. There has been a decline in Candida infections but Aspergillus species predominate. Other mold pathogens including Fusarium, Scedosporium, and Zygomycetes also cause infections in lung transplant recipients. Furthermore, the widespread use of antifungal prophylaxis has prompted a delay in onset of Aspergillus infection in lung transplant recipients. Pulmonary parenchymal disease has become the most common manifestation of invasive aspergillosis. Among the risk factors pre- or posttransplant Aspergillus colonization is the most important risk factor reported in several retrospective studies. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. Other factors that have been reported include preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplantation. The risk factors for other mold infections such as Scedosporium, Fusarium, and Zygomycetes are not well studied. The best antimold prophylaxis strategy and choice of drug remains to be elucidated. Most lung transplant centers use either voriconazole or inhaled amphotericin preparations. However, data have emerged regarding the increased risk of squamous cell cancer in lung transplant recipients on voriconazole prophylaxis. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in a significant decrease in mortality.

Risk factors for voriconazole hepatotoxicity at 12 weeks in lung transplant recipients.

Voriconazole is commonly used for prophylaxis and treatment of invasive aspergillosis in lung transplant recipients. However, the use of voriconazole may at times be limited by the development of hepatotoxicity. Our goal is to determine predictors of voriconazole-associated hepatotoxicity in lung transplant recipients. We conducted a single center retrospective cohort study of lung transplant recipients from 2006 to 2010 who received voriconazole therapy. We compared characteristics of patients who developed hepatotoxicity and those who did not. One hundred five lung transplant recipients received voriconazole. Hepatotoxicity occurred in 51% (54/105) of patients and lead to discontinuation in 34% (36/105). In univariate analysis, age less than 40 years, cystic fibrosis, use of azathioprine, history of liver disease and early initiation of voriconazole were associated with hepatotoxicity. In multivariable logistic regression analysis, perioperative initiation of voriconazole (within 30 days of transplantation) was independently associated with hepatotoxicity (OR 4.37, 95% CI: 1.53-12.43, p = 0.006). The five risk factors identified in the univariate analysis were used to build a K-nearest neighbor algorithm predictive model for hepatotoxicity. This model predicted hepatotoxicity with an accuracy of 70%. Voriconazole therapy initiated within the first 30 days of transplantation is associated with a greater risk of developing hepatotoxicity.

Post renal transplantation Kaposi's sarcoma: a review of its epidemiology, pathogenesis, diagnosis, clinical aspects, and therapy.

BACKGROUND: Kaposi's sarcoma (KS) is a vascular malignancy primarily involving the skin. This neoplasm occurs commonly in acquired immunodeficiency syndrome (AIDS) and post solid organ transplantation. Human herpesvirus type 8 (HHV-8) has been shown to play a causative role in AIDS-associated KS and in post renal transplantation KS. METHODS: Based on a MEDLINE search, we present a review of the current information on the epidemiology, pathogenesis, diagnosis and treatment of post-transplantation KS (PT-KS) with an emphasis on renal transplantation. RESULT: The different frequencies of PT-KS in different parts of the world seem to be related to seroprevalence of HHV-8 infection. Following renal transplantation and the administration of immunosuppressive therapy, HHV-8 may reactivate. The renal tubular epithelium is a site for HHV-8 latency. Rates of PT-KS in seropositive recipients and anti-HHV-8 mismatched recipients (donor+/recipient-) are approximately 13% and 4.6%, respectively. Additional risk factors for the development of PT-KS include skin color, country of birth, age at the time of transplantation, and different induction regimens including anti-thymocyte globulin, steroid, or anti-interleukin 2-receptor antagonists. Skin is the major site of involvement. Surprisingly, involvement of the transplanted organ has been reported to be extremely rare. Reduction in immunosuppressive therapy and switching to mammalian targets of rapamycin inhibitors, such as sirolimus, are effective treatments for PT-KS. In patients with no response to reduction in immunosuppressive therapy, systemic chemotherapy with different regimens has been reported to be successful. CONCLUSION: PT-KS in renal transplant patients is an important problem specifically in southern Europe and the Middle East. In the majority of patients, the diagnosis based on clinical suspicion is always essential. Clinicians should bear in mind that PT-KS may threaten graft function and hence result in rejection complications. Appropriate management increases patient survival.

Hepatitis C core Ag and its clinical applicability: potential advantages and disadvantages for diagnosis and follow-up?

Chronic hepatitis C virus (HCV) infection which is often a silent disease has resulted in a global epidemic. The diagnosis of hepatitis C virus often requires confirmation with molecular techniques such as the polymerase chain reaction for detection of HCV RNA. Following laboratory confirmation of the diagnosis, molecular techniques are routinely used to monitor HCV RNA levels, particularly in those undergoing treatment. Unfortunately, molecular tests are relatively expensive and their cost may be prohibitive in the developing world. Several studies have investigated the applicability of the hepatitis C core Ag (HCVcAg), as a substitute for measuring HCV RNA levels. In this review, we provide an overview of the major findings of these studies focused on the utility of measuring HCVcAg antigen levels in the clinical setting. Overall, measuring HCVcAg levels is associated with several advantages and disadvantages. It may be useful in different clinical settings for monitoring HCV patients after obtaining an initial baseline HCV RNA result.

Fungi and molds following lung transplantation.

The landscape of fungal infections in lung transplant recipients has significantly changed over the course of time. The initial predominance of CANDIDA species has given way to the prominence of ASPERGILLUS species in the current era followed by other mold infections, namely, SCEDOSPORIUM and Zygomycetes, which are emerging as newer pathogens. CRYPTOCOCCUS NEOFORMANS is another important pathogen responsible for the morbidity in lung transplant recipients. The use of widespread antifungal prophylaxis directed against the mold infections has resulted in delayed onset of invasive aspergillosis in lung transplant recipients. In recent studies cumulative incidence rate of invasive aspergillosis was noted to be 2.4% at 12 months. Invasive mold infections in lung transplant may present as tracheobronchitis, invasive pulmonary infections, or disseminated disease. Invasive pulmonary infections are now the most common manifestations of mold infections, followed by tracheobronchitis. Pre- or posttransplant ASPERGILLUS colonization, along with preceding cytomegalovirus infections, hypogammaglobulinemia, and single-lung transplants are considered significant risk factors for invasive aspergillosis. Recently posttransplant colonization has been implicated in the development of bronchiolitis obliterans syndrome. The appropriate antimold prophylaxis strategy, by the use of either voriconazole or inhaled amphotericin, remains to be fully determined. Advances in the diagnosis and treatment of invasive aspergillosis have resulted in significant decreases in mortality. The risk factors for other mold infections such as SCEDOSPORIUM or Zygomycetes are being elucidated. Infections with these organisms, however, carry mortality up to 80%. The current article reviews the changes in the epidemiology of invasive molds and CRYPTOCOCCUS infections and other emerging fungal pathogens and highlights the controversies surrounding antifungal prophylaxis in lung transplant recipients.

GB virus type C infection in hemodialysis patients considering co-infection with hepatitis C virus.

GB virus type C is a well-known viral agent with capability of infecting patients undergoing hemodialysis. Liver enzyme levels in infected individuals have been reported to remain within the normal range. Simultaneous infection of GBV-C and other viral agents may occur due to common routes of transmission. A total of 104 hemodialysis patients living in Tehran were included in this case-control study (53 patients with HCV infection, group I; and 51 with no HCV infection, group II). Diagnosis was made by detection Anti-E(2) protein using ELISA and HCV-RNA using RT-PCR. History of HBV-infection, organ transplantation, depression, malignancies, chemotherapy, diabetes mellitus, thyroid disorders and chronic cutaneous disorders were considered. Patients were evaluated for high- risk behaviors such as intravenous drug injection, addiction or substance abuse. A total of 14 patients (13.6%) were GBV-C-infected. Four of them were co-infected with HCV. All patients with GBV-C infection had viral genotype 2. Thirteen patients (12%) had a history of multiple blood transfusions. Mean (+/-SD) age of GBV-C-infected patients was 48.7+/-13.8 years. Among GBV-C infected patients, three patients had a history of organ transplantation and three had a co-morbidity of diabetes mellitus. This study as the first case-control study to evaluate the association between GBV-C and HCV infection, to our knowledge, shows hemodialysis patients living in Tehran are infected with GBV-C with intermediate level of frequency. The association of GBV-C transmission with other viral blood-borne agents might be necessary.

The risk factors and laboratory diagnostics for post renal transplant tuberculosis: a case-control, country-wide study on definitive cases.

BACKGROUND: Tuberculosis (TB) is an important cause of morbidity and mortality in renal transplant recipients and, because of its infrequency and the lack of medical awareness, it is usually misdiagnosed. This study was carried out to determine frequency and weight of multiple risk factors for post kidney transplantation TB. METHODS: A total of 44 cases (0.3%), out of 12,820 patients from 12 major kidney transplantation centers in Iran from 1984 to 2003, were compared with 184 healthy transplant subjects who were transplanted by the same surgical team. RESULTS: The mean age of cases and controls was 37.7 (13-63) and 35.6 (8-67) years (P=0.3), respectively. The mean duration of pre-transplantation hemodialysis was 30.3 (3-168) months in cases and 18.2 (1-180) months in controls (P=0.03). A positive past history of TB was detected in 2 cases and 1 control (P=0.3). The mean doses of initial and maintenance immunosuppressive drugs in cases and controls were not significantly different. A total of 25 cases (56.8%) and 60 controls (32.6%) had rejection before diagnosis of TB (P=0.004; OR=2.7, CI(95%): 1.3-5.6). CONCLUSIONS: To our knowledge, this is the first study that demonstrated an increase in the risk of post-transplant TB by increasing the duration of pre-transplant hemodialysis and the number of post-transplant rejection episodes as 2 immunocompromised states. Further study is needed to clarify our new findings, specifically in relation to different immunosuppressive regimens.

Slow graft function after pediatric renal transplantation from volunteer live donors.

Slow graft function (SGF) may occur during the early post-transplant period. In this paper, we present our findings regarding SGF after pediatric renal transplantation and its predictive variables. From 1985 to 2004, a total of 300 pediatric renal transplants were performed at our institution. A total of 10 cases with SGF and 50 controls that were operated by the same surgeons were enrolled in this study. The mean age of the recipients and donors was 11.4 (3-15 yr) and 28.05 yr (20-50 yr), respectively. All kidneys were retrieved from living donors. We compared patients with SGF with controls regarding four independent variables: age difference between donors and recipients, serum hemoglobin difference between donors and recipients, mean blood pressure (systolic blood pressure + 2 [diastolic blood pressure]/3) difference between donors and recipients, and weight difference between donors and recipients. The mean age of recipients was 10.5 +/- 4.1 in SGF group and 11.6 +/- 2.5 in control group (p = 0.4). The differences between donors and recipients regarding weight and mean blood pressure in subjects with SGF were not higher than other patients (42 kg vs. 37.4 kg, p = 0.4; -3 mmHg vs. -4.1 mmHg, p = 0.8). The mean hemoglobin difference between donors and recipients was 6.3 +/- 2.1 g/dL in SGF group and 6.7 +/- 2.3 g/dL in control group (p = 0.6). The differences between donors and recipients regarding age, weight, mean blood pressure and serum hemoglobin level are not predictive variables for SGF.

Does pre-transplantation antireflux surgery eliminate post-renal transplantation pyelonephritis in children?

PURPOSE: Antireflux surgery for VUR before renal transplantation decreases the risk of post-kidney transplant UTI in pediatric patients with primary vesicoureteral reflux. We studied the risk of post-kidney transplant UTI in patients with or without surgical correction of VUR before transplantation compared to patients without VUR. MATERIALS AND METHODS: We compared 12 patients who had VUR corrected before transplantation (group 1) to 17 patients with VUR who did not undergo antireflux surgery before transplantation (group 2) and 36 patients undergoing renal transplantation without VUR (group 3). A total of 10 patients in group 1 (83.3%) and 10 in group 2 (58.8%) had high grade VUR. RESULTS: Eight patients in group 1 (66.7%), 6 in group 2 (35.3%) and 33 in group 3 (91.7%) remained free of febrile UTI during followup (p = 0.00). Among patients with high grade VUR 6 in group 1 and 1 in group 2 remained UTI-free (p = 0.02). A total of 33 patients in the control group (91.7%) remained free of febrile UTI, an incidence that was significantly lower compared to group 1 (p = 0.03) and group 2 (p = 0.00). Of the patients with high grade VUR 3 in group 1 (30%) and 4 in group 2 (40%) experienced recurrent febrile UTIs (p = 0.64). CONCLUSIONS: Even after surgical correction of VUR before transplantation the frequency of febrile UTI remained higher than that in kidney transplant recipients without VUR. In cases of high grade VUR reimplantation before renal transplantation decreased the rate of febrile UTI but it was still higher than the level of risk in the control group.

Ureteroscopic management of urological complications after renal transplantation.

OBJECTIVE: To determine the feasibility, safety and efficacy of diagnostic and therapeutic ureteroscopy in renal allograft ureters. MATERIAL AND METHODS: We reviewed 1560 consecutive renal allografts performed between June 1989 and February 2002. A total of 28 patients (1.8%) had indications for an endoscopic procedure on the allograft ureter, as follows: obstructive ureteral calculi with a history of failed extracorporeal shock-wave lithotripsy, n=6; suspected ureteral stricture, n=3; upwardly migrated ureteral stents, n=9; and ureteral stricture at the ureteroneocystostomy site, n=10. Ureters were anastomosed to the bladder using the Leadbetter-Politano and Lich-Gregoire methods in six and 22 cases, respectively. Ureteroscopies were performed with a semi-rigid 9.8 F Wolf ureteroscope. RESULTS: Identification of the ureteral orifice and insertion of a guide-wire into it was successful in 19 cases (68%). If we exclude the 10 patients with ureteral stricture, ureteroscopy was successful in 13/18 cases (72%). Four ureteral calculi (67%) were removed with the ureteroscope. Seven out of nine migrated stents (78%) were retrieved. Four patients with ureteral stricture at the ureteroneocystostomy site (40%) underwent successful ureteral dilatation and double-J ureteral catheters were also inserted. Diagnostic ureteroscopy was successful in all cases. Two complications (one urinary leakage and one symptomatic urinary tract infection) occurred and were managed conservatively. CONCLUSIONS: Ureteral endoscopy is a safe and effective method for the management of urological complications after renal transplantation. This procedure can be considered the first choice, in preference to percutaneous and antegrade modalities.

Outcome of Kaposi's sarcoma and graft following discontinuation of immunosuppressive drugs in renal transplant recipients.

PURPOSE: Owing to the use of immunosuppressive drugs, renal transplant recipients are at risk for malignancies including Kaposi's sarcoma (KS). Following the diagnosis, physicians tend to decrease the doses of immunosuppressive drugs to lower tumor progression rate. On the other hand, those who receive lower doses of immunosuppressive drugs are at a higher risk for acute rejection. In this study, we evaluated the outcome of KS on renal allografts following discontinuation or decrease in the doses of drugs. METHODS: Since 1984, 14 (nine men and five women) among 2000 cases of renal transplantation have been diagnosed as KS. In 11 patients, cyclosporine was completely discontinued, the dosage was decreased to half of the initial dose in other cases. Except one case, we discontinued either azathioprine or mycophenolate mofetil. RESULTS: During 57 months of follow-up on average, the serum creatinine level remained normal in 10 but increased in four cases. Kidney function deteriorated in two of these four patients at the beginning of study. Three patients died with normal serum creatinine levels. Discontinuation of immunosuppressive drugs caused complete remission of KS in all patients except one who received chemotherapy. CONCLUSION: Discontinuation of immunosuppressants following the diagnosis of KS caused complete remission of this cancer in almost all patients and seemed to be relatively safe for kidney graft function.

A comparison between laparoscopic and open pyeloplasty in patients with ureteropelvic junction obstruction.

INTRODUCTION: Our aim was to compare clinical and radiological outcomes, complications, and hospital stay in laparoscopic and open pyeloplasty. MATERIALS AND METHODS: From February 2002 to February 2003, 69 patients with ureteropelvic junction obstruction (UPJO) were assigned into two groups. Thirty-seven patients underwent transperitoneal laparoscopic pyeloplasty and 32 underwent open surgical pyeloplasty. Clinical symptoms were assessed before and after surgery, subjectively. Radiological assessment was also done three months postoperatively. RESULTS: Mean operative time was 3.2 hours and 2.2 hours in laparoscopic and open pyeloplasty groups, respectively. Intraoperative bleeding was trivial in both groups and no complication or conversion to open surgery occurred. Postoperative complication rates were 24% and 6% in laparoscopic and open pyeloplasty groups, respectively. Mean hospital stay was similar (6.2 days) in the two groups. Mean follow-up was 16.5 months versus 11.4 months. Clinical and radiological success rates were 89% and 83.8% for laparoscopy group versus 96.5% and 87% for open pyeloplasty group. Due to recurrence of stricture, repeated surgery was performed in 4 patients of laparoscopy and 1 of open pyeloplasty groups. CONCLUSION: Laparoscopic pyeloplasty is a less invasive method with less pain, cosmetic advantages, no long incision, and outcome comparable with open surgery. Hospital stay is also not longer than that in open surgeries. Hence, laparoscopic pyeloplasty can be a substitute for skilled surgeons.