Isolated vascular "v" lesions in liver allografts: How to approach this unusual finding.

According to the Banff criteria for kidney allografts, isolated vascular or "v" lesions are defined as intimal inflammation, age-inappropriate fibro-intimal hyperplasia, or both, without the presence of associated interstitial T cell-mediated rejection (TCMR). In general, these lesions portend a worse outcome for kidney allografts, particularly in those where the "v" lesions are identified in patients with coexistent donor specific antibodies (DSA) or later after transplantation. Although affected arteries are rarely sampled in liver allograft biopsies, we identified nine patients at a mean of 1805 days posttransplantation and compared these to matched controls. Almost half (4 of 9) of the study patient biopsies showed inflammatory arteritis associated with focal or diffuse C4d positivity, which was not observed in matched controls. One "v" lesion patient progressed to rejection-related graft failure and two developed moderate/severe TCMR in subsequent biopsies, whereas only one rejection episode occurred in follow-up biopsies, and no rejection-related deaths or graft failures were detected in controls. In conclusion, patients with liver allograft isolated "v" lesions should undergo further evaluation and closer follow-up for impending TCMR and/or underlying co-existent chronic antibody-mediated rejection (AMR).

Pediatric intestinal transplant listing criteria - a call for a change in the new era of intestinal failure outcomes.

Current listing indications used for intestinal transplantation (IT) were proposed in 2001. We undertook the present single center study to see if these criteria are still valid. The 2001 criteria (advanced cholestasis, loss of >50% central venous catheter (CVC) sites, ≥2 sepsis/year, ultrashort bowel) were compared in children with intestinal failure in old era-1998-2005 (N = 99) to current era-2006-2012 (N = 91) to predict the need for IT using sensitivity, specificity, NPV and PPV. Two 2001 criteria had poorer predictive value in the current era: Advanced cholestasis (PPV 64% old vs. 40% current era; sensitivity 84% vs. 65%, respectively) and ultrashort bowel (PPV 100% old vs. 9% current era; sensitivity 10% vs. 4%, respectively). Three newly proposed criteria had high predictive value: ≥2 ICU admissions (p = 0.0001, OR 23.6, 95% CI 2.7-209.8), persistent bilirubin >75 mmol/L despite lipid strategies (p = 0.0005, OR 24.0, 95% CI 3.2-177.4), and loss of ≥3 CVC sites (p = 0.0003, OR 33.3, 95% CI 18.8-54.0). There was 98% probability of needing IT when two of these new criteria were present. The 2001 IT criteria have limited predictive ability in the current era and should be revised. A multicenter study is required to validate the findings of this single center experience.

Simultaneous liver-pancreas transplantation for cystic fibrosis-related liver disease: a multicenter experience.

BACKGROUND: Diabetes is associated with increased morbidity and mortality in patients with cystic fibrosis (CF). While liver transplantation is well established for CF-related liver disease (CFLD), the role of simultaneous liver-pancreas transplantation is less understood. METHODS: We polled 81 pediatric transplantation centers to identify and characterize subjects who had undergone simultaneous liver-pancreas transplantation and obtain opinions about this procedure in CFLD. RESULTS: Fifty (61.7%) polled transplant centers responded and 94% reported that they would consider simultaneous liver-pancreas transplantation for CFLD and diabetes. A total of 8 patients with simultaneous liver-pancreas transplantation were identified with median follow up of 38 months. All patients had pre-existing diabetes. Exocrine and endocrine pancreatic function was initially restored in all patients with later functional loss in one patient. Body mass index Z-score increased between one year pre-transplantation and one year post-transplantation (P=0.029). CONCLUSIONS: Patients with CFLD undergoing initial assessment for liver transplantation may benefit from consideration of simultaneous liver-pancreas transplantation.

Basiliximab with delayed introduction of calcineurin inhibitors as a renal-sparing protocol following liver transplantation in children with renal impairment.

Renal impairment is frequently compromised in patients with end-stage liver disease and is associated with increased long-term mortality post-LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal-sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre-LT renal impairment within the first year (cGFR: 135 mL/min/1.73 m2 vs. 144 mL/min/1.73 m2 ; p = 0.56) or at 5-8 yr following LT, (129 mL/min/1.73 m2 vs. 130 mL/min/1.73 m2 ; p = 0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal-sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long-term kidney function.

Hematopoietic stem-cell transplantation following solid-organ transplantation in children.

Reports of hematopoietic stem-cell transplantation (HSCT) following solid-organ transplantation have been described in adults mainly as case reports. These reports demonstrate feasibility but likely do not reflect true outcomes due to a positive reporting bias. We report herein the outcomes of all our pediatric recipients of allogeneic HSCT following previous solid-organ transplantation between 2000 and 2009. Four children were identified. Two patients underwent heart transplantation followed by cord-blood allogeneic HSCT for T-cell lymphoma/post transplant lymphoproliferative disease (PTLD) and two patients underwent liver transplantation followed by living-donor allogeneic HSCT for severe aplastic anemia (SAA). The mean time between transplants was 4.2 years (range 1.5-6 years). All patients engrafted; however, all patients died from 37 days to 1 year after HSCT. Causes of death included infections (n=2), multi-organ failure (n=1) and solid-organ graft rejection (n=1). Though three patients survived beyond day+100, multiple complications were observed including EBV re-activation followed by EBV-positive PTLD (n=1) and five episodes of severe infections. The patients transplanted for lymphoma did not have evidence of recurrence at last follow-up. Although feasibilty has been shown with this cohort, we conclude that allogeneic HSCT in immunosuppressed patients following solid-organ transplantation remains a very high risk procedure that results in severe morbidity and mortality in children.

The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation.

Routine prophylaxis for CMV with valganciclovir is common in adult recipients but data to support its use in children are scarce. The aim of this study was to compare the efficacy and safety of valganciclovir vs. ganciclovir in a pediatric cohort. We performed a retrospective analysis of 92 children after KTx and/or LTx. All children have received IV ganciclovir for two wk, and then oral ganciclovir (TID; n = 41) before 2004, or valganciclovir (OD; n = 51) thereafter. Treatment was given for three months in R+/D+ or R+/D- recipients and for six months in R-/D+. Patients were followed for one yr post transplant. Both groups were comparable in their demographic and transplant-related history. Symptomatic CMV infection/disease developed in 13.7% vs. 19.5% of valganciclovir and ganciclovir groups, respectively (P-NS). Time-to-onset of CMV infection was comparable in both groups (P-NS); rates of acute allograft rejection were similar in both groups (3.9% vs. 9.8%). Risk factors for CMV infection included young age, serostatus of R-/D+, and allograft from cadaver donor. No significant side effects were noted in both groups. As in adults, valganciclovir appears to be as efficacious and safe as oral ganciclovir. Valganciclovir should be considered as a possible prophylactic treatment for CMV in pediatric recipients of KTx or LTx.

Long-term follow-up of portal hypertension after liver transplantation in children.

We aimed to describe the long-term changes in the imaging and clinical features of PHALT in children. A retrospective review was undertaken of consecutive children undergoing their first liver transplant between 1993 and 2003. Details of clinical progress and ultrasound imaging were recorded at one-yr post-transplantation and at last follow-up. Data were extracted on 83 children (median age at transplant 1.7 yr, range one month to 17.5 yr, 44 girls) who underwent 89 transplants. Four of these children died at a mean 5.6 yr (range 3.8-6.9 yr) after transplantation. Of the survivors, follow-up at one yr (n = 83) and at last follow-up (n = 71, median 4.3 yr post-transplant) revealed imaging evidence of splenomegaly in 46% and 44%, ascites in 6% and 4%, and portal systemic collaterals in 12% and 14%, respectively. Gastrointestinal hemorrhage associated with portal hypertension had occurred in no children at one yr and in four (6%) at latest follow-up. Features of portal hypertension on ultrasound scan are common in children before liver transplantation. An important minority of children will suffer clinically significant complications of PHALT during long-term follow-up, caused by both vascular and parenchymal disease.

Lactic dehydrogenase isoenzyme in cerebrospinal fluid of children with febrile convulsions.

AIM: To study the lactic dehydrogenase isoenzyme values in children with simple and complex febrile convulsions. METHODS: Cerebrospinal fluid samples were collected from 115 children, 57 with simple febrile convulsions, 27 with complex febrile convulsions and 31 with no neurological or intracranial pathology (controls). Lactic dehydrogenase activity and isoenzyme levels were measured on a Hitachi analyser. RESULTS: Mean total lactic dehydrogenase activity was similar in the three groups. In the control group, lactic dehydrogenase-1 was the main fraction, followed by lactic dehydrogenase-2 and lactic dehydrogenase-3; only small percentages of lactic dehydrogenase-4 and lactic dehydrogenase-5 were detected. In the febrile convulsion group, the lactic dehydrogenase-1 fraction percentage was lower and lactic dehydrogenase-2, lactic dehydrogenase-3 percentages were higher than those in the control group; and the differences were statistically significant between the control and study groups (p < 0.01). Values of lactic dehydrogenase-4 and lactic dehydrogenase-5 were similar in all three groups. CONCLUSION: This is the first report on the lactic dehydrogenase isoenzyme pattern in the cerebrospinal fluid of patients with simple and complex febrile convulsions. The important finding that focal and general febrile convulsions are not associated with cell damage and changes in aerobic and anaerobic metabolism as lactic dehydrogenase remained unchanged. Analysis of cerebrospinal fluid lactic dehydrogenase isoenzyme levels can assist clinicians in differentiating febrile convulsions from clinical situations that might mimic them.

Bacterial susceptibility to oral antibiotics in community acquired urinary tract infection.

BACKGROUND: The most common oral antibiotics used in the treatment of urinary tract infection (UTI) are sulphonamides and cephalosporins, but emerging resistance is not unusual. AIMS: To assess the change in susceptibility of urinary pathogens to oral antibiotics during the past decade in children with community acquired UTI. METHODS: The study sample included two groups of children with a first community acquired UTI: 142 children enrolled in 1991 and 124 enrolled in 1999. UTI was diagnosed by properly collected urine specimen (suprapubic aspiration, transurethral catheterisation, or midstream specimen in circumcised males) in symptomatic patients. Antimicrobial susceptibility of the isolates was compared between the two groups. RESULTS: The pathogens recovered in the two groups were similar: in 1991--E coli 86%, Klebsiella 6%, others 8%; in 1999--E coli 82%, Klebsiella 13%, and others 5%. A slight but generalised decrease in bacterial susceptibility to common antibiotics in the two groups was shown: ampicillin 35% versus 30%; cephalexin 82% versus 63% (p < 0.001); nitrofurantoin 93% versus 92%. The only exception was co-trimoxazole, 60% versus 69%. Overall resistance to antibiotics in 1999 was as follows: ampicillin 70%, cephalexin 37%, co-trimoxazole 31%, amoxicillin-clavulanate 24%, nitrofurantoin 8%, cefuroxime-axetil 5%, nalidixic acid 3%. CONCLUSIONS: This study shows a slight but generalised decrease in bacterial susceptibility to common oral antibiotics in the past decade in our population. Empirical initial treatment with co-trimoxazole or cephalexin is inadequate in approximately one third of UTI cases. A larger number of pathogens may be empirically treated with amoxicillin-clavulanate (24% resistance); 95% of organisms are susceptible to cefuroxime-axetil.

Herpetic whitlow infection in a general pediatrician--an occupational hazard.

Herpetic whitlow is a well-known occupational hazard for medical staff. It has been reported to affect mainly workers in intensive care units who come into close contact with oral secretions. We report herpetic whitlow infection in a general pediatrician in order to increase the awareness to this infectious occupational hazard that might occur in any health care worker who deals with oral secretions. A 35-year-old male general pediatrician sustained a minor knife cut in his finger and 5 days later he developed herpetic whitlow. He was treated with acyclovir with gradual improvement. We review the clinical course, complications and treatment of herpetic whitlow. The source of the infection in the present case was unknown, but it probably derived from oral secretions of children with unrecognized infection. Simple measures like wearing gloves during oral examination will avoid unnecessary morbidity in medical staff.

Clinical dysentery in hospitalized children.

BACKGROUND: Clinical dysentery is a severe presentation of an enteric infection. The aim of the study was to evaluate the impact of a serious bacterial etiology in clinical dysentery in hospitalized children and determine if children at high risk can be identified on the basis of clinical or laboratory parameters. PATIENTS AND METHODS: A prospective study design was used. The study population included 60 children admitted to our department with clinical dysentery over a 16-month period. Fresh stool specimens were collected on days 1, 2 and 3. The clinical and laboratory data of the children were analyzed. RESULTS: Clinical dysentery accounted for 1.7% of all pediatric hospitalizations during this period. Stool cultures were positive for Shigella spp. in 18 children (30%), and Salmonella spp. in 15 children (25%), Campylobacter jejuni was identified in one patient (2%). There were no significant differences in clinical characteristics or laboratory parameters between children with positive and negative stool cultures. CONCLUSION: 40% of the children hospitalized for clinical dysentery were eligible for antibiotic treatment. Early administration of empiric antibiotic treatment is justified in children hospitalized for clinical dysentery in Israel. Clinical or laboratory parameters were unable to differentiate those with clinical dysentery at risk of serous bacterial pathogens in stool.

Carbohydrate metabolism in primary growth hormone resistance (Laron syndrome) before and during insulin-like growth factor-I treatment.

Among 43 patients with Laron syndrome followed in our clinic, we were able to study the carbohydrate metabolism from infancy into adult age in 30 patients. During infancy, fasting blood glucose levels were in the hypoglycemic range (mean +/- SD, 3.5 +/- 1.2 mmol/L) and increased at the end of a delayed puberty to 4.6 +/- 0.6 mmol/L. Fasting plasma insulin was higher than expected for concomitant glucose levels, and several of the 20 patients who underwent an oral glucose tolerance test (OGTT) had glucose intolerance and relatively high insulin levels. In adult patients, insulinopenia developed and one 38-year-old patient developed non-insulin-dependent diabetes mellitus (NIDDM) with subsequent need for insulin therapy. Continuous insulin-like growth factor-I (IGF-I) treatment of a pubertal patient with glucose intolerance and hyperinsulinemia normalized both responses. In conclusion, long-term IGF-I deficiency leads to insulin resistance, which is reversed by exogenous IGF-I administration.