Minimally invasive pediatric surgery: Increasing implementation in daily practice and resident’s training

Background In 1998, the one-year experience in minimally invasive abdominal surgery in children at a pediatric training center was assessed. Seven years later, we determined the current status of pediatric minimally invasive surgery in daily practice and surgical training. Methods A retrospective review was undertaken of all children with intra-abdominal operations performed between 1 January 2005 and 31 December 2005. Results The type of operations performed ranged from common interventions to demanding laparoscopic procedures. 81% of all abdominal procedures were performed laparoscopically, with a complication rate stable at 6.9%, and conversion rate decreasing from 10% to 7.4%, compared to 1998. There were six new advanced laparoscopic procedures performed in 2005 as compared to 1998. The children in the open operated group were significantly smaller and younger than in the laparoscopic group (p < 0.001 and p = 0.001, respectively). The majority (64.2%) of the laparoscopic procedures were performed by a trainee. There was no difference in the operating times of open versus laparoscopic surgery, or of procedures performed by trainees versus staff surgeons. Laparoscopy by trainees did not have a negative impact on complication or conversion rates. Conclusions Laparoscopy is an established approach in abdominal procedures in children, and does not hamper surgical training.     

Association of mild to moderate kidney dysfunction and coronary calcification

Coronary artery calcification (CAC) is prevalent and predicts mortality among patients with ESRD, but whether less severe kidney dysfunction is associated with CAC is uncertain. To address this question, 6749 participants of the Multi-Ethnic Study of Atherosclerosis, who were middle-aged and without known cardiovascular disease, were evaluated. Renal function was categorized by cystatin C quartiles and estimated GFR (eGFR; < to >60 ml/min per 1.73 m(2)), and CAC was evaluated by computed tomography (CT). Fifty percent of participants had CAC, mean cystatin C was 0.90 mg/L, and 10% had eGFR <60 ml/min per 1.73 m(2). In unadjusted analysis, kidney dysfunction by either measure was strongly associated with CAC; however, the associations were lost after adjustment for age, gender, race, hypertension, and IL-6 (relative risk 1.04 [95% confidence interval 0.97 to 1.11] for the highest cystatin C quartile compared with the lowest, and relative risk 1.03 [95% confidence interval 0.98 to 1.08] for eGFR below compared with above 60 m/min per 1.73 m(2)). Similarly, neither higher cystatin C nor eGFR <60 was associated with severity of CAC. These results suggest that a higher burden of CAC is unlikely to explain the association between mild to moderate kidney dysfunction and cardiovascular mortality.     

No association of seropositivity for anti-Borrelia IgG antibody with mental and physical complaints

Undiagnosed chronic Lyme disease caused by Borrelia burgdorferi is considered a differential diagnoses in medically unexplained symptoms like arthralgias, distal paresthesias, depressive symptoms, lack of concentration and fatigue. The aims of the study were to assess the association of mental and physical complaints with seropositivity for anti-Borrelia IgG in a general population sample. Seropositivity indicated an infection with Borrelia in the past. The Study of Health in Pomerania was conducted in a community living in a region with endemic Lyme disease. Mental and physical complaints were assessed on 38 items with the von Zerssen's complaint scale. IgG antibodies to Borrelia were determined by ELISA in 4264 individuals. Seropositivity was analyzed applying two cut-off scores (>5 and >10 IU/ml). IgG antibodies to Borrelia were found positive in 388 subjects (9.1%) applying the >5 IU/ml cut-off and in 130 subjects (3.0%) applying the >10 IU/ml cut-off. In multivariate analyses (MANCOVA), both definitions of seropositivity were not associated with increased mental or physical complaints while adjusting for gender, age, employment status, rural residency, physical activity, diabetes mellitus and number of chronic diseases. In the general population, seropositivity for anti-Borrelia IgG antibodies was not associated with an increase of self-rated mental or physical complaints or impairments. Therefore, clinicians should not overvalue seropositivity for anti-Borrelia IgG as a medical cause for unexplained mental or physical complaints.     

Diagnostic yield of electroencephalograms in infants and young children with frequent paroxysmal eye movements

Paroxysmal eye movement events are common in children. Many infants and young children are referred for a routine or a video-electroencephalography study. When epileptic, these events form part of a seizure and rarely occur as an isolated ictal event. The yield of the electroencephalogram in determining the nature of isolated paroxysmal eye movement episodes has not been reported. We reviewed our experience with video-electroencephalography studies in patients referred for paroxysmal eye movements. Twenty-one cases were analyzed, of which almost half were cognitively normal. All video-electroencephalography studies captured events that were found to be nonepileptic, including 6 records with interictal epileptiform activity. The semiology of the events differed between cognitively impaired individuals, who had more lateral eye deviation episodes, and normal patients, who showed blinking as a major manifestation. In conclusion, video-electroencephalography studies are probably not indicated in infants and young children with paroxysmal eye movements as their sole complaint.     

Cellular stress triggers the human topoisomerase I damage response independently of DNA damage in a p53 controlled manner

The 'human topoisomerase I (htopoI) damage response' was reported to be triggered by various kinds of DNA lesions. Also, a high and persistent level of htopoI cleavage complexes correlated with apoptosis. In the present study, we demonstrate that DNA damage-independent induction of cell death using colcemid and tumor necrosis factor alpha is also accompanied by a strong htopoI response that correlates with the onset of apoptotic hallmarks. Consequently, these results suggest that htopoI cleavage complex formation may be caused by signaling pathways independent of the kind of cellular stress. Thus, protein interactions or signaling cascades induced by DNA damage or cellular stress might lead to the formation of stabilized cleavage complexes rather than the DNA lesion itself. Finally, we show that p53 not only plays a key role in the regulation of the htopoI response to UV-C irradiation but also to treatment with colcemid.     

Reference values for hair cotinine as a biomarker of active and passive smoking in women of reproductive age, pregnant women, children, and neonates: systematic review and meta-analysis

Exposure to environmental tobacco smoke (ETS) is most often estimated using questionnaires, but they are unreliable. Biomarkers can provide valid information on ETS exposure, the preferred biomarker being cotinine. However, no reference range of hair cotinine exists to distinguish among active, passive, and unexposed nonsmokers. This study identifies cutoffs to validate cotinine as a marker for exposure to ETS. Data were obtained from six databases (four US, one Canada, one France). Active smoking and exposure to ETS were measured in the hair of women of reproductive age, pregnant women, their children, and neonates. Subjects were classified into active smokers, passively exposed to ETS, and unexposed nonsmokers. A total of 1746 cases were available for analysis. For active smokers, mean hair cotinine concentrations (95% confidence interval) were 2.3 to 3.1 ng/mg for nonpregnant women and 1.5 to 1.9 ng/mg for pregnant women. In the group of passive smokers, mean hair cotinine concentrations were 0.5 to 0.7 ng/mg for nonpregnant women, 0.04 to 0.09 ng/mg for pregnant women, 0.9 to 1.1 for children, and 1.2 to 1.7 for neonates. Among unexposed nonsmokers, mean hair cotinine was 0.2 to 0.4 ng/mg in nonpregnant women, 0.06 to 0.09 ng/mg in pregnant women, and 0.3 to 0.4 ng/mg in children. Cutoff values for hair cotinine were established to distinguish active smokers from passive or unexposed (0.8 ng/mg for nonpregnant women and 0.2 ng/mg for pregnant women). A cutoff value of 0.2 ng/mg was accurate in discriminating between exposed children and unexposed. These new values should facilitate clinical diagnosis of active and passive exposure to tobacco smoke. Such diagnosis is critical in pregnancy and in a large number of tobacco-induced medical conditions.     

The pharmacokinetic profile of sitaxsentan, a selective endothelin receptor antagonist, in varying degrees of renal impairment

What is already known about this subject

• The initial indication for endothelin (ET) receptor antagonism as a treatment strategy, primary pulmonary hypertension, is now expanding to include scleroderma, which can cause both pulmonary and renal disease.
• It is important to understand the effects of impaired renal function on the pharmacokinetics of these drugs to allow appropriate dosing in individuals with impaired renal function.

What this study adds

• Sitaxsentan, an oral selective endothelin A receptor antagonist, is licensed for the treatment of pulmonary hypertension, and studies of this drug in CKD are planned.
• The pharmacokinetic profile of sitaxsentan is unchanged in subjects with varying degrees of renal impairment.
• The results of this study will allow confident dosing of sitaxsentan in individuals with renal impairment, and inform future studies.

Aim

To investigate the pharmacokinetic profile of a single 100-mg oral dose of sitaxsentan, a selective endothelin type A receptor antagonist, in subjects with normal and impaired renal function.

Methods

This was an open label, single oral dose study in subjects with normal [creatinine clearance (CrCL) ≥ 80 ml min⁻¹] and impaired renal function (mild renal impairment CrCL 51–80 ml min⁻¹, moderate impairment CrCL 31–50 ml min⁻¹, severe impairment CrCL ≤ 30 ml min⁻¹). All subjects received a dose of 100 mg sitaxsentan.

Results

Twenty-four subjects were enrolled, six in each of the normal and three renal impairment groups. The mean plasma sitaxsentan concentrations were comparable across the groups, as were the mean values for C_max (10.3–13.9 µg ml⁻¹), AUC_∞ (18.7–22.5 h µg⁻¹ ml⁻¹), oral clearance (CL/F, 82.3–94.9 ml min⁻¹), volume of distribution (Vz/F, 64.8–69.6 l) and elimination half-life (t_1/2, 8.6–9.6 h). There was substantial overlap among the four groups in the individual subject values for CL/F and Vz/F and no relationship between either of these parameters and CrCL.

Conclusion

After a single 100-mg oral dose of sitaxsentan there were no differences in its pharmacokinetics among subjects with normal or impaired renal function.     

Left atrial disc device thrombosis after atrial defect closure with the Gore® Cardioform septal occluder: A case series

Device thromboses after patent foramen ovale (PFO) and atrial septal defect (ASD) closure are rare but serious complications. They have been reported in different devices of virtually all manufacturers. Here, we report three cases of left atrial device thrombosis after atrial defect closure with the Gore® Cardioform septal occluder (GSO) in our recent institutional experience. All patients were symptomatic with new-onset neurological impairments and evidence of cerebral thromboembolism. Device thromboses have occurred despite antiplatelet therapy in two patients and moreover were observed late, at approximately 2 years after implantation, in two patients. One device was surgically explanted while in two cases, thrombi completely resolved with initiated anticoagulation. All patients had a favorable neurological recovery. Our observations suggest that regular follow-up echocardiography beyond 6 months after device implantation might be advisable in patients with GSO devices to rule out late device thromboses. More long-term follow-up data considering safety and late complications of contemporary PFO and ASD devices is required to establish confident evidence-based recommendations on long-term follow-up management and antithrombotic therapy regimen after PFO and ASD closure.     

Detection and outcomes of substance use disorders in adolescents seeking mental health treatment

OBJECTIVE: To compare detection rates, service use, and outcomes of substance use disorder (SUD) in adolescents seeking mental health treatment. METHOD: Adolescents (n = 237) and their parents or caregivers completed parallel, self-administered versions of the Adolescent Treatment Outcomes Module (ATOM) at intake and 6-month follow-up. SUD was assessed using the Diagnostic Interview Schedule for Children (DISC). RESULTS: Although 42 (16.6%) adolescents seeking mental health treatment met DISC criteria for any SUD at baseline, clinicians detected only 19 of these (kappa = 0.51). Sensitivity and specificity were high for a screening tool for adolescent SUD (95.2 and 82.0, respectively). Adolescents with undetected SUD were less likely to receive SUD services and to have more legal problems at 6-month follow-up compared to adolescents with detected SUD. CONCLUSIONS: SUD rates may be high in adolescents seeking mental health treatment, confirming the need for routine screening in this population. Results confirm that a large gap exists between the need for and access to SUD treatments, which may contribute to poorer outcomes for all adolescents with SUD.