Population Pharmacokinetics of Intravenous and Oral Acyclovir and Oral Valacyclovir in Pediatric Population To Optimize Dosing Regimens.

Acyclovir is an antiviral currently used for the prevention and treatment of herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. This study aimed to characterize the pharmacokinetics (PK) of acyclovir and its oral prodrug valacyclovir to optimize dosing in children. Children receiving acyclovir or valacyclovir were included in this study. PK were described using nonlinear mixed-effect modeling. Dosing simulations were used to obtain trough concentrations above a 50% inhibitory concentration for HSV or VZV (0.56 mg/liter and 1.125 mg/liter, respectively) and maximal peak concentrations below 25 mg/liter. A total of 79 children (212 concentration-time observations) were included: 50 were taking intravenous (i.v.) acyclovir, 22 were taking oral acyclovir, and 7 were taking both i.v. and oral acyclovir, 57 for preventive and 22 for curative purposes. A one-compartment model with first-order elimination best described the data. An allometric model was used to describe body weight effect, and the estimated glomerular filtration rate (eGFR) was significantly associated with acyclovir elimination. To obtain target maximal and trough concentrations, the more suitable initial acyclovir i.v. dose was 10 mg/kg of body weight/6 h for children with normal renal function (eGFR ≤ 250 ml/min/1.73 m2) and 15 to 20 mg/kg/6 h for children with augmented renal clearance (ARC) (eGFR > 250 ml/min/1.73 m2). The 20-mg/kg/8 h dose for oral acyclovir and valacyclovir produced effective concentrations in more than 75% of children; however, a 15-mg/kg/6 h dose, if possible, is preferred. These doses should be prospectively confirmed, and therapeutic drug monitoring could be used to refine them individually. (This study has been registered at ClinicalTrials.gov under identifier NCT02539407.).

Acute chest syndrome after laparoscopic splenectomy in children with sickle cell disease: operative time dependent?

BACKGROUND: Laparoscopic splenectomy remains a technically demanding procedure. On patients with sickle cell disease (SCD), a post operative acute chest syndrome (ACS) can occur. The aim of the study was to look for predictive factors of post operative ACS. PATIENTS AND METHOD: It's a retrospective study on patients with SCD, who underwent a laparoscopic splenectomy in Robert Debré hospital, Paris, France, between March 2008 and December 2013. Diagnosis of ACS was done if the patient developed hypoxemia associated with fever above 38.5 °C and an infiltrate on chest x ray during the post operative course. Pre-, post- and operative factors were studied. Descriptive statistics were compared using the Mann-Whitney test or the exact Fisher test. A p inferior to 0.05 was considered as significant. RESULTS: 52 patients with SCD underwent a laparoscopic splenectomy. Twelve patients presented a post operative ACS (23%) (mean age at surgery 4 years old) while forty did not (mean age 5.25 years old). Neither previous episode of ACS nor any factors reflecting SCD severity were significant. The shorter the operative time was, the greater the risk of developing an ACS (p < 0.05). CONCLUSION: ACS is an important complication following laparoscopic splenectomy in patients with SCD. The immediate post operative management, in the absence of predictive factors for ACS, should be carefully followed in a high dependency unit at least for 48 h for all patients.

Paediatric and adolescent traumatic gastrointestinal injuries: results of a European multicentre analysis.

AIM: Paediatric gastrointestinal injuries (GIIs) are rare, and the aim of this multicentre study was to evaluate their outcomes in a large cohort. METHODS: Hospital databases of 10 European paediatric surgical centres were reviewed for paediatric traumatic GIIs managed between 2000-2010. RESULTS: Ninety-seven patients with a median age of 9 years (0-17 years) were identified, with 72 blunt and 25 penetrating GIIs. Initial diagnostics in 90 patients led to correct diagnosis in 71%. Diagnostics were delayed in 26 patients (median 24 h). Eighty-two patients required surgery (67 laparotomy, 12 laparoscopy and three other approaches). There was a 50% conversion in the laparoscopic group. Median hospital stay was 10 days (range 1-137 days), with longer duration influenced by associated injuries (n = 41). Diagnosis <24 h was associated with significantly shorter hospital stay compared to more than 24 h (p = 0.011). In one-third of patients, morbidities were not related to a diagnostic delay or type of injury. There were five lethal outcomes, four due to associated injuries. CONCLUSION: Initial diagnostics in traumatic paediatric GIIs provide false negatives in one-third of patients. Diagnostic delay <24 h is associated with a significantly shorter hospital stay. Although laparoscopy is associated with a conversion rate of 50%, it can be used for diagnosis in suspected cases to avoid nontherapeutic laparotomy.

The impact of anorectal malformations on anorectal function and social integration in adulthood: report from a national database.

AIM: The impact of anorectal malformation (ARM) on bowel function and social, educational and occupational end-points was investigated in adult patients entered on a national database. METHOD: Data from a national database of adult patients operated on between 1962 and 1999 for ARM were analysed. The database Malformations Ano-rectales et Pelviennes rares (MAREP) was part of a common information system, CEMARA, on rare congenital disorders. A self-administered questionnaire regarding bowel function, academic qualifications, employment and family status was mailed to patients. The type of ARM, subsequent follow-up and management including surgical interventions were retrospectively retrieved from medical records. RESULTS: Of 210 adult patients on the registry since 2008, 68 were included in this study. Only three (8.5%) had had regular follow-up. All reported some disturbance in bowel function. The fertility rate of 1.5 children per woman did not differ from the general population. CONCLUSION: Anorectal malformation ARM often leads to suboptimal bowel function in adulthood. This has an impact on social integration.

Morphological mosaicism of the pancreatic islets: a novel anatomopathological form of persistent hyperinsulinemic hypoglycemia of infancy.

BACKGROUND: Morphological studies of the pancreas in persistent hyperinsulinemic hypoglycemia of infancy (PHHI) have focused on the diagnosis of focal vs. diffuse forms, a distinction that determines the optimal surgical management. ABCC8 or KCNJ11 genomic mutations are present in most of them. AIM: Our aim was to report a new form of PHHI with peculiar morphological and clinical characteristics. RESEARCH DESIGN AND METHODS: Histopathological review of 217 pancreatic PHHI specimens revealed 16 cases morphologically different from diffuse and focal forms. They were analyzed by conventional microscopy, quantitative morphometry, immunohistochemistry, and in situ hybridization. RESULTS: Their morphological peculiarity was the coexistence of two types of islet: large islets with cytoplasm-rich ß-cells and occasional enlarged nuclei and shrunken islets with ß-cells exhibiting little cytoplasm and small nuclei. In small islets, ß-cells had abundant insulin content but limited amount of Golgi proinsulin. Large islets had low insulin storage and high proinsulin production and were mostly confined to a few lobules. No evidence for K(ATP) channels involvement or 11p15 deletion was found. Genomic mutations for ABCC8, KCNJ11, and GCK were absent. Patients had normal birth weight and late hypoglycemia onset and improved with diazoxide. Ten were cured by limited pancreatectomy. Six recurred after surgery and were medically controlled. CONCLUSION: This new form of PHHI is characterized by a morphological mosaicism. Pathologists should recognize this mosaicism on intraoperative frozen sections because it is often curable by partial pancreatectomy. The currently unknown genetic background does not involve the classical genomic mutations responsible for diffuse and focal PHHI.

Tungiasis: a poorly documented tropical dermatosis.

Tungiasis is the parasitic skin disease caused by the sand flea Tunga penetrans, also called the jigger flea, found in most intertropical countries. The contamination occurs when walking barefoot in the sand: adult females actively burrow the foot epidermis leading to self-limited lesions responsible for itching or pain. The diagnosis is made on clinical observation and history of travelling to an endemic country. The simple treatment is surgical extraction of the flea.

Large congenital transmesenteric hernia: a missed small-bowel atresia?

Internal hernias are uncommon diagnoses and represent rare causes of intestinal obstruction. Diagnoses are frequently made perioperatively. We present herein an illustrated case of transmesenteric hernia diagnosed in a pregnant woman who consulted for severe abdominal and dorsal pains. As CT scan was not possible because of the obstetric history, a decision to perform surgery was made because of acute pain, no history of previous surgery, and a plain erect X-ray disclosing early signs of intestinal obstruction. Perioperative findings were an ileal volvulus through a transmesenteric fossa circled by a unique ileocolic branch. This particular vascular disposition suggests transmesenteric hernias may be the first step in the constitution of congenital small-bowel atresia.

Long-term outcome of laparoscopic Nissen-Rossetti fundoplication for neurologically impaired and normal children.

BACKGROUND: This study aimed to assess the long-term effects of laparoscopic Nissen-Rossetti fundoplication (LNF) on clinical and pH evaluations of children with gastroesophageal reflux disease (GERD) according to neurologic status. METHODS: The study examined 127 children (73 neurologically impaired and 54 neurologically normal with primary GERD) who consecutively underwent LNF from 1992 to 2003. The follow-up protocol included evaluations at 3, 15, and more than 36 months (long-term evaluation) postoperatively, which consisted of physical examination and 24-h pH monitoring. Recurrences were defined as abnormal pH-metry exhibited by symptomatic children. RESULTS: The long-term follow-up period averaged 5.5 years. Of the 73 neurologically impaired children, 9 (12%) had GERD recurrences, which occurred during the evaluation period and required redo surgery in four cases, including two Bianchi procedures. In the neurologically normal group, one recurrence (2%) occurred 3 months after surgery. The long-term complications in this group included dyspepsia (n = 3), occasional dysphagia (n = 2), gas bloat syndrome (n = 1), and alimentary disorders (n = 2). CONCLUSIONS: For children with primary GERD, LNF is a long-term efficient procedure. For the neurologically impaired children, the results were good, with more than 85% of the children symptom free after 5 years, although repeated evaluations are required to diagnose late recurrences related to evolving dysmotility disorders.

Retroperitoneoscopic nephroureterectomy of a horseshoe kidney in a child.

Retroperitoneoscopic heminephrectomy used to manage a horseshoe kidney in a 15-month-old boy is reported. The surgery was decided after a progressive increase of arterial blood pressure in the patient followed for poor kidney functioning resulting from vesicoureteral reflux in both ureters of the left duplex moiety of a horseshoe kidney. The retroperitoneoscopy was conducted with three trocars: a 10-mm port inserted under direct vision at the extremity of the left 12th rib and two 5-mm operating trocars. Division of the isthmus was performed using an ultrasonic scalpel. Duration of the pneumoretroperitoneum was 115 min. The patient was discharged on postoperative day 4. At 2 years postoperatively, the patient's arterial blood pressure was normal without treatment. The authors conclude that retroperitoneoscopic nephrectomy for horseshoe kidney is safe and feasible in children, offering all the advantages of minimally invasive surgical procedures.

Acute repair of the anterior cruciate ligament with lateral capsular augmentation.

Forty-seven patients had primary repair and extraarticular augmentation with a lateral loop of the iliotibial tract for acute rupture of the ACL. (All of these patients had anterolateral rotatory instability (ALRI) preoperatively as diagnosed by a positive jerk test.) Of these 47 patients, 36 were available for follow-up evaluation. Followup ranged from 6 to 68 months (average, 21.6 months). Twenty-three of the patients (64%) were rated as excellent or good. Ten of the patients (27.8%) were rated as fair, and three patients (8%) were rated as poor. Thirty-three of the 36 patients (91%) were objectively free of ALRI as tested by the jerk test and had 1+ or less result in a Lachman test, with a firm end point. Only one patient felt his knee to be unstable (he had a positive pivot jerk). More than 90% of the patients returned to sport, and 72% returned at their preinjury level.

Posterior pelvic disruptions managed by the use of the Double Cobra Plate.

From five years of experience with 30 patients on whom the Double Cobra plate technique was employed for reconstruction of a variety of acute and late posterior pelvic injuries, this method appears to be highly suitable for effective stabilization of both sacral fractures and bilateral sacroiliac dislocations. With late presentations and larger individuals, associated anterior reconstruction of the pelvic ring is strongly recommended. The surgical complications have been sufficiently uncommon to recommend more widespread application of the protocol. Nevertheless, the potential for major complications, including life-threatening problems associated with pelvic reconstruction, should not be underestimated. These surgical techniques of internal fixation are potentially formidable undertakings that should be limited to those surgeons who possess appropriate training, instrumentation, and experience.

The use of the Putti-Platt procedure in the treatment of recurrent anterior dislocation. With special reference to the young athlete.

This study presents the results of 107 shoulder reconstructions by one surgeon, of which 59 were Putti-Platt procedures, and 48 were combined Putti-Platt/Bankhart procedures. The patients were predominately young males engaged in contact sports, particularly the Rugby football codes. There were nine redislocations noted in clinical records for the 107 Putti-Platt or combined Putti-Platt procedures, but 8 noted on the 71 replies to a questionnaire. There was only one redislocation in the absence of significant trauma. The average loss of external rotation was 20 degrees in the 41 patients that were able to present for reexamination. Sixty-two of the 71 patients who answered questionnaires were able to play any sport without functional impairment. The Putti-Platt procedure provides excellent shoulder stability for active sportsmen without significant loss of performance.