Determinants of early surgical complications after pediatric liver transplantation: A single center/single surgeon experience over 20 years.

BACKGROUND: The risk of early surgical complications of liver transplantation (LT) is higher in children when compared with adults. The aims of the present retrospective study from a single center cohort/single surgeon were to identify the predictive factors for surgical complications after pediatric LT. METHODS: All children receiving a first LT from October 1990 to October 2010 in our center were included. RESULTS: Included 151 children (boys 55.0%), with a mean age of 4.8 ± 4.8 years, and a mean weight of 17.9 ± 14.4 kg. Thirty-seven patients were transplanted within the first year, and 59 patients had a body weight below 10 kg. The main initial liver disease was biliary atresia (49.0%). Living donor LT was performed in 39 cases (25.8%), cadaveric whole liver LT in 50 cases (33.1%), and cadaveric partial liver LT in 62 cases (41.1%). Early surgical complications included reoperation (37.8%), vascular complications (8.6%), i.e. arterial (3.3%) or portal thrombosis/stenosis (7.3%) within the first month, and biliary complications in the first 90 days occurred in 22.5% of the cases. The main indications for surgical revision were abdominal bleeding, treatment of a biliary complication, and bowel perforation. Multivariate analysis disclosed that only graft type (split and moreover from a living donor) was significantly and independently associated with the occurrence of biliary complication, and that indication for LT, period, graft type, and operative time were significantly and independently associated with the necessity of surgical revision. CONCLUSION: Our results emphasize that surgical complications are frequent and strongly depend on patient/graft characteristics.

Are protocol graft biopsies after pediatric liver transplantation useful? Experience in a single center over 20 years.

BACKGROUND: The role of protocol liver biopsies (PLB) in the follow-up of pediatric liver transplant recipients remains questionable. This single-center retrospective study aimed to evaluate their clinical impact on the long-term management of pediatric liver transplant recipients. METHODS: We described histopathological lesions and clinical consequences for patient management of PLB performed 1, 5, 10, 15, 20, and 25 years after pediatric liver transplantation (LT). RESULTS: A total of 351 PLB performed on 133 patients between 1992 and 2021 were reviewed. PLB found signs of rejection in 21.7% of cases (76/351), and moderate to severe fibrosis in 26.5% of cases (93/351). Overall, 264 PLB (75.2%) did not cause any changes to patient care. Immunosuppression was enhanced after 63 PLB, including 23 cases of occult rejection. The 1-year PLB triggered significantly more changes, while biopsies at 15, 20, and 25 years produced the lowest rates of subsequent modifications. PLB had a significantly higher probability of inducing therapeutic changes if the patient had abnormal biological or imaging results (odds ratio [OR] 2.82 and 2.06), or a recent history of rejection or bacterial infection (OR 2.22 and 2.03). CONCLUSION: Our results suggest that, although it often does not prompt any treatment changes, PLB could be performed because of its ability to detect silent rejection requiring an increase in immunosuppression. PLB could be carried out 1, 5, and 10 years after LT and then every 10 years in patients with normal biological and imaging results and no recent complications, while other patients could be kept on a 5-year protocol.

A structured curriculum and procedure clinic to help family medicine residents diagnose and treat skin cancer.

Melanoma is a potentially deadly type of skin cancer that has been increasing in incidence but is curable if found in the early stages. Family physicians are in an ideal situation to examine the skin during routine visits, but studies indicate they are not well trained to detect or treat skin cancers. We piloted a structured, longitudinal, hands-on procedural curriculum to improve family medicine residents' ability to identify and manage skin cancers. Family medicine residency programs wishing to improve the diagnosis and management of skin cancer by family physicians might consider trialing our structured curriculum and procedure clinic.

Le mélanome est un type de cancer de la peau potentiellement mortel qui est de plus en plus fréquent, mais qui est guérissable sous réserve d'une détection précoce. La visite de routine chez le médecin de famille est l'occasion idéale pour examiner la peau. Les études indiquent toutefois que les médecins de famille n'ont pas le niveau de formation nécessaire pour détecter et traiter les cancers de la peau. Nous avons piloté un programme structuré longitudinal axé sur la pratique visant à améliorer la capacité des résidents en médecine familiale à identifier et à traiter ce type de cancer. Nous invitons les responsables de programmes de résidence en médecine familiale qui souhaitent améliorer le diagnostic et la prise en charge des cancers cutanés par les médecins de famille à expérimenter notre programme structuré sur les procédures cliniques.

Efficacy and safety of prolonged-release tacrolimus in stable pediatric allograft recipients converted from immediate-release tacrolimus - a Phase 2, open-label, single-arm, one-way crossover study.

There are limited clinical data regarding prolonged-release tacrolimus (PR-T) use in pediatric transplant recipients. This Phase 2 study assessed the efficacy and safety of PR-T in stable pediatric kidney, liver, and heart transplant recipients (aged ≥5 to ≤16 years) over 1 year following conversion from immediate-release tacrolimus (IR-T), on a 1:1 mg total-daily-dose basis. Endpoints included the incidence of acute rejection (AR), a composite endpoint of efficacy failure (death, graft loss, biopsy-confirmed AR, and unknown outcome), and safety. Tacrolimus dose and whole-blood trough levels (target 3.5-15 ng/ml) were also evaluated. Overall, 79 patients (kidney, n = 48; liver, n = 29; heart, n = 2) were assessed. Following conversion, tacrolimus dose and trough levels remained stable; however, 7.6-17.7% of patients across follow-up visits had trough levels below the target range. Two (2.5%) patients had AR, and 3 (3.8%) had efficacy failure. No graft loss or deaths were reported. No new safety signals were identified. Drug-related treatment-emergent adverse events occurred in 28 patients (35.4%); most were mild, and all resolved. This study suggests that IR-T to PR-T conversion is effective and well tolerated over 1 year in pediatric transplant recipients and highlights the importance of therapeutic drug monitoring to maintain target tacrolimus trough levels.

mTOR inhibitors in pediatric liver transplant recipients.

BACKGROUND: During the past decade, mTOR inhibitors (mTORi), everolimus and sirolimus, have been increasingly used after adult liver transplantation (LT). The aim of the present study was to describe the use of mTORi in pediatric LT recipients. METHODS: All pediatric LT recipients who received mTORi before December 2017 from 4 European pediatric LT centers were included and analyzed. RESULTS: The present retrospective study included 30 patients; 21 were male (70%), median age was 9.3 years (range: 1.2-17.1 years) at mTORi introduction. Main indications for mTORi introduction were pre-existing liver malignancy (43.3%), calcineurin inhibitor (CNI) nephrotoxicity (26.7%), or rejection (23.4%). At last follow-up, mTORi CNIs were withdrawn in 10 patients (10/29, 34.5%). The median dose of mTORi was 1.8 mg/day (range: 0.3-5.0) or 0.058 mg/kg/day (range: 0.01-0.26), and the median trough level was 5.1 µg/L (range: 1.0-15.5). After a median follow-up of 2.8 years (range: 0.2-10.0), 50.0% of the patients presented with at least one adverse event. The main adverse events included hyperlipidemia, proteinuria, dermatitis, and mucitis. Overall mTORi discontinuation rate was 23.3% (10.0% because of adverse event). Introduction of mTORi had no significant impact on renal function. CONCLUSION: Our results suggest that mTORi can be used in pediatric LT recipients in different clinical situations, both to reinforce immunosuppressive therapy, and to reduce CNI and related toxicity.

Sertraline as an Additional Treatment for Cholestatic Pruritus in Children.

OBJECTIVES: Pruritus is a severe symptom accompanying chronic cholestasis. It can be debilitating and difficult to control. In children, first-line treatments are ursodeoxycholic acid and rifampicin. Refractory pruritus may require invasive therapies including liver transplantation. Clinical trials based on small samples of adult patients suggest that serotonin reuptake inhibitors can improve pruritus in cholestatic or uremic disease. We performed a prospective, multicenter study to assess efficiency and safety of the serotonin reuptake inhibitor sertraline in treating children with refractory cholestatic pruritus. METHODS: Twenty children experiencing refractory cholestatic pruritus related to Alagille syndrome or progressive familial intrahepatic cholestasis were included from 4 centers between 2007 and 2014, and treated with sertraline at a starting dose of 1 mg ·â€Škg ·â€Šday and thereafter individually adapted up to 4 mg ·â€Škg ·â€Šday. Before and after 3 months with therapy, pruritus was assessed using a visual itching scale graded on 10 points, a skin scratch marks score and a sleeping impairment score. RESULTS: Sertraline was prescribed at a median daily dose of 2.2 mg ·â€Škg ·â€Šday. After 3 months, pruritus improved in 14 out of 20 treated patients, and the median itching score decreased significantly from 8/10 (5-10) to 5/10 (2-10). Likewise, skin scratch marks and sleep quality improved in 9 of these 14 patients. Nonsevere adverse events were reported in 6 children, leading to treatment discontinuation in 3. CONCLUSION: Our data suggest that sertraline may constitute a useful drug in the management of refractory cholestatic pruritus in children.

Lipid profile and cardiovascular risk factors in pediatric liver transplant recipients.

Cardiovascular diseases induce long-term morbidity and mortality of adult LT recipients. The aim of this retrospective study was to assess CVRF, lipid abnormalities, and atherosclerosis (appraised by c-IMT), more than 10 yr after pediatric LT. Thirty-one children who underwent LT between December 1990 and December 2000 were included. Median age at LT was 14 months (range 4-64), and median follow-up after LT was 11.9 yr (range 9.0-17.3). In our cohort, obesity (9.7%) and treated hypertension (9.7%) were rare. None of the patients was smoker or diabetic. High TC and TG were both observed in 6.5% of the patients. The mean c-IMT for male patients was 1.22 ± 1.55 and 1.58 ± 1.23 mm in female patients. Seven patients (22%) had a mean c-IMT above +2 s.d. Values below the 5th percentile were noted for LDL-cholesterol (58.1%), HDL-cholesterol (25.8%), apolipoprotein B (40%), and apolipoprotein A1 (20%). LDL-cholesterol and apolipoprotein B levels were significantly lower in patients treated by tacrolimus in comparison with CsA (p < 0.05). In conclusion, our results suggest that pediatric LT patients do not present significant CVRF; moreover, instead of hyperlipidemia, hypocholesterolemia (LDL-C) is frequent and immunosuppressive therapy is probably the cause.

Acute leukemia presenting as acute hepatitis without liver failure.

A diagnosis of acute lymphoblastic or myeloblastic leukemia was made in 6 children ages 4 to 14 years who presented with a clinicobiochemical picture of acute hepatitis without liver failure. Standard chemotherapy, including 1 week pretreatment with steroids in children with lymphoblastic leukemia, allowed complete remission of the leukemia and normalization of serum liver tests.

Severe dysphagia in children with eosinophilic esophagitis and esophageal stricture: an indication for balloon dilation?

BACKGROUND: Esophageal stricture is one of the most severe complications in eosinophilic esophagitis (EoE). Clinical practice is based on limited data and some treatments are still considered controversial. We report on our experience in the treatment of severe dysphagia and esophageal strictures in EoE, especially using balloon dilation, showing the clinical practice in our pediatric population. PATIENTS AND METHODS: This was a single-center retrospective study between December 2002 to November 2007, identifying all of the pediatric patients with severe dysphagia in the context of EoE. Demographic data and the results of various treatment regimens were reviewed. RESULTS: Severe dysphagia was identified in 13 cases (77% male, mean age 12.8 +/- 4.4 years). Endoscopic findings were mucosal edema (62%), long segment strictures, esophagitis, and off-white appearance in 31%. Histologically, >20 eosinophils per high-power field were present in all of the patients. Medical treatment consisted of proton pump inhibitor PPI (77%), montelukast (31%), local corticosteroids (54%), systemic corticosteroids (8%), elemental diet (15%), and food elimination diet (61%). A combined therapeutic approach was performed in all of the cases, due to clinical relapse or no response to monotherapy. Good response was obtained clinically in 70%, endoscopically in 62%, and histologically in 75%. Relapses were observed in 46% of the cases. Balloon dilation was necessary in 31% of the cases (mean dilation sessions 3.3 +/- 0.95), being effective in 100% of patients, without complications. CONCLUSIONS: In our pediatric series, combined medical (corticosteroids, elemental diet, and food elimination diet) and endoscopic approach (repeated balloon dilation) were effective and safe in patients with severe EoE and esophageal stricture.

Endoscopic treatment of gastroesophageal varices in young infants with cyanoacrylate glue: a pilot study.

BACKGROUND: In children, endoscopic sclerotherapy and variceal ligation (EVL) are the most used techniques for the treatment of gastroesophageal variceal bleeding (VB). However, these techniques achieve poor results in cases of gastric variceal bleeding, and EVL is not applicable in young infants. OBJECTIVE: Our purpose was to evaluate the feasibility, efficacy, and safety of cyanoacrylate glue injection for the treatment of gastroesophageal varices in young infants. DESIGN: Single-center prospective study. PATIENTS: From 2001 to 2005, 8 young infants (

Hands on: is there an association between doing procedures and job satisfaction?

OBJECTIVE: To determine whether there is a relationship in family medicine between higher overall job satisfaction and doing a wider range of procedures. DESIGN: Secondary analysis of a population survey (mailed questionnaire) using multiple regression analysis. SETTING: Canadian family practices. PARTICIPANTS: Family physicians who responded to the 2001 National Family Physician Workforce Survey conducted by the College of Family Physicians of Canada and whose main practice settings were private offices or clinics, community clinics, community health centres, or academic family medicine teaching units. MAIN OUTCOME MEASURES: Family physicians' overall job satisfaction. The predictor variable was range of procedures performed, defined as the variety of procedures done by family physicians. Eight potential confounding variables were examined: age; sex; solo versus group practice; population served by practice (urban, semiurban, rural); number of medical services offered; teaching (yes, no); constraints to medical care services; and the balance of physicians' personal and professional commitments. RESULTS: Of 19,762 physicians who responded to the question on job satisfaction, 15.8% were dissatisfied, 54.3% were moderately satisfied, and 29.8% were very satisfied overall. In multiple regression analysis, when controlling for confounding variables, the range of procedures done by family physicians was significantly associated with overall job satisfaction (P = .0001). The larger the range of procedures, the more satisfied the physician. The percentage of those very satisfied ranged from 28.1% for family physicians who did only a few procedures (0 to 4) to 33.5% for those who did 10 or more procedures. Greater satisfaction was reported by very young and very old male physicians, those in solo practice, rural physicians, teachers, those who had fewer constraints to medical care services, and those who thought their balance of personal and professional commitments was about right. CONCLUSION: Family physicians might improve their overall job satisfaction by increasing the range of procedures they do. This modest association has not been described previously.

Unexpected diagnosis of cystic fibrosis at liver biopsy: a report of four pediatric cases.

We report here four cases of pediatric patients in whom the diagnosis of cystic fibrosis was made only after the histological examination of a liver specimen obtained by biopsy (three cases) or at autopsy (one case). There were two boys and two girls, aged 13 months to 7.5 years. None had a personal or familial history suggestive of cystic fibrosis. One patient, presenting with myocardial lesion and hepatomegaly, died of heart failure; at autopsy, the liver showed a typical aspect of focal biliary cirrhosis. In the three other cases, liver disease was the only manifestation of cystic fibrosis at the time of diagnosis. Liver biopsy examination showed focal biliary cirrhosis in one case and massive steatosis in two. In all four cases, the diagnosis was confirmed by the existence of known pathogenic mutations in the CFTR gene. The evolution was variable; one patient had progressive liver disease with severe portal hypertension after 7 years; another one had lung complications after 1 year. In conclusion, our experience recalls that the diagnosis of cystic fibrosis must be considered in children presenting with unexplained liver disease; its confirmation by molecular techniques makes it possible to set up an appropriate follow-up.

[Eosinophilic esophagitis: 3 case reports]. / Oesophagites à oesinophiles: à propos de trois observations.

Eosinophilic esophagitis is a rare entity, characterized by eosinophilic infiltration of the oesophagal mucosae, with no gastroesophageal reflux. Food allergies are often involved. We report 3 paediatric cases of eosinophilic esophagitis, revealed by dysphagia, with or without stricture. Eosinophilic esophagitis is a rare disease, but its frequency is probably underestimated. Symptoms are sometimes unusual. Oesogastroscopy with biopsy is essential for the diagnosis. Food allergies can be involved and must be systematically investigated.

Urological manifestations associated with chronic intestinal pseudo-obstructions in children.

PURPOSE: Chronic intestinal pseudo-obstruction syndrome is a rare pathological condition characterized by chronic intestinal occlusion without any anatomical or mechanical lesion. Recent progress in the treatment of these children has led to improved survival and development of associated urological complications. We define urological manifestations of chronic intestinal pseudo-obstruction to optimize evaluation and treatment. MATERIALS AND METHODS: We evaluated retrospectively the charts of 20 girls and 19 boys with a mean age of 11.2 years (range 3 days to 26 years) diagnosed with chronic intestinal pseudo-obstruction from January 1975 to February 2000. Urological evaluation included prenatal and postpartum ultrasonography, serum renal function assessment, voiding cystourethrography and urodynamics. RESULTS: Urological involvement was present in 27 of the 39 children (69%). Megacystis in 26 children (96.3%) was isolated in 12 (46.2%) and associated with ureterohydronephrosis in 14 (53.8%), including 4 with vesicoureteral reflux. One patient presented with a complex urinary anomaly. Prenatal diagnosis of megacystis was made in 16 patients (59%), including 4 with neonatal urinary retention and 12 with urinary tract infection. At followup 24 patients had 1 or greater febrile urinary tract infections while 3 had afebrile infections. In the 14 patients with megacystis and ureterohydronephrosis, 3 or greater febrile urinary tract infections developed while 10 patients with isolated megacystis had only 1 febrile urinary tract infection. Twelve patients underwent 17 urodynamic studies, all of whom initially presented with hypocontractile detrusor, increased age corrected capacity (194% +/- 44%) and compliance (42 ml./cm. H O, range 13 to 214). Bladder proprioception was also diminished. Presently voiding is achieved by abdominal pressure in 14 cases and intermittent catheterization in 10. Antibioprophylaxis was given to 17 patients, at one point in time. Renal failure (1 iatrogenic, 1 complex anomaly) developed in 2 patients. CONCLUSIONS: The presence of megacystis on prenatal ultrasound should alert the physician to the possibility of chronic intestinal pseudo-obstruction. Bladder adynamia represents the dominant urological complication. Urological evaluation and management are required to ensure adequate bladder emptying to reduce the risk of urinary tract infection and preserve long-term renal function.

Manejo farmacológico de algunos problemas asociados al trauma craneo-encefálico / Pharmacological management of several dysfunctions related to traumatic brain injury

El presente trabajo constituye una recopilación de los avances en el manejo farmacológico de varias disfunciones asociadas al traumatismo cerebral, en la fase sub-aguda de recuperación. Se ofrecen varias alternativas de tratamiento, debiendo considerarse una guía para el manejo terapéutico de pacientes con secuelas de trauma cráneo-encefálico en la etapa subaguda de rehabilitación