Thomas Jack

CNS or Bone Marrow Involvement As Risk Factors for Poor Survival in Post-Transplantation Lymphoproliferative Disorders in Children After Solid Organ Transplantation

PURPOSE To identify prognostic factors of survival in pediatric post-transplantation lymphoproliferative disorder (PTLD) after solid organ transplantation. PATIENTS AND METHODS A multicenter, retrospective case analysis of 55 pediatric solid organ graft recipients (kidney, liver, heart/lung) developing PTLD were reported to the German Pediatric-PTLD registry. Patient charts were analyzed for tumor characteristics (histology, immunophenotypes, cytogenetics, Epstein-Barr virus [EBV] detection), stage, treatment, and outcome. Probability of overall and event-free survival was analyzed in defined subgroups using univariate and Cox regression analyses. RESULTS PTLD was diagnosed at a median time of 29 months after organ transplantation, with a significantly shorter lag time in liver (0.83 years) versus heart or renal graft recipients (3.33 and 3.10 years, respectively; P = .001). The 5-year overall and event-free survival was 68% and 59%, respectively, with 59% of patients surviving 10 years. Stage IV disease with bone marrow and/or CNS involvement was associated independently with poor survival (P = .0005). No differences in outcome were observed between early- and late-onset PTLD, monomorphic or polymorphic PTLD, and EBV-positive or EBV-negative PTLD, respectively. Patients with Burkitt or Burkitt-like PTLD and c-myc translocations had short survival (< 1 year). CONCLUSION Stage IV disease is an independent risk factor for poor survival in pediatric PTLD patients. Prospective multicenter trials are needed to delineate additional risk factors and to assess treatment approaches for pediatric PTLD.

Characteristics of Early and Late Ptld Development in Pediatric Solid Organ Transplant Recipients

Background Posttransplantation lymphoproliferative disorders (PTLD) present a major cause of mortality and morbidity after solid organ transplantation. The purpose of this study was to identify the factors associated with the development of early- and late-onset PTLD in pediatric solid organ transplant recipients. Methods We examined the medical history, laboratory parameters, and pathology of 127 children with PTLD who were registered in the German multicenter pediatric PTLD registry. Data were collected retrospectively from 1991 to 2003 and prospectively from 2004 onward. We compared early (<1 year) and late (>1 year) PTLD using survival analysis. Results The median time to PTLD was 3.00 (95% confidence interval, 2.12–3.26) years. Forty-two patients developed PTLD within the first year after transplantation (early PTLD) and 85 patients developed PTLD after 1 year (late PTLD). Early PTLD development was associated with younger age (P=0.0016), extranodal disease (P=0.019), graft organ involvement (P=0.0065), and immunosuppressive regimens including tacrolimus (P=0.001) or mycophenolate (P=0.0025). Most early PTLD patients experienced graft rejection before PTLD diagnosis (P=0.0081). Early PTLD was often of B-cell lymphoma histology (P=0.024) and tended to be Epstein-Barr virus positive (P=0.052). In contrast, Burkitt’s lymphoma (P=0.0047) and Hodgkin’s disease (P=0.016) were only observed in late PTLDs, which are more likely to present with nodal disease (P=0.019). Overall survival and event-free survival were not significantly different between early and late PTLD. Conclusion Early and late childhood PTLD have distinct characteristics. Whereas early PTLD appears mainly as an Epstein-Barr virus–driven disease especially favored by insufficient immunosurveillance, late PTLD often resembles tumors with distinct pathogenetic alterations and nodal appearance.

Concept of "awake venovenous extracorporeal membrane oxygenation" in pediatric patients awaiting lung transplantation.

In patients awaiting LuTx, MV and ECMO are often the last ways to create a bridge to LuTx. Both interventions are associated with a poor posttransplant outcome and survival rate. To improve the results of these patients, new “bridging‐strategies” are necessary. Recent reports demonstrate promising results for the concept of “awake ECMO” in adult patients. To date, no data on this approach in pediatric patients have been available. We therefore describe the use of VV‐ECMO as a treatment strategy for RF in awake pediatric patients. It presents our experiences with the first three children treated using this new concept. Mean amount of time on ECMO was 44 days (range, 11.5–109 days). Two patients were successfully bridged to their LuTx. Both are still alive without any recurrences (24 and three months following LuTx). One patient died before a further LuTx after 109 days on ECMO due to adenoviral infection. Although reintubation was necessary in two patients, and total time being awake while on ECMO was <50%, we conclude that the concept of “awake VV‐ECMO” is feasible for the treatment of RF and can be used as a “bridging therapy” to LuTx.

Takotsubo Cardiomyopathy in a 2-Year-Old Girl: 3-Dimensional Visualization of Reversible Left Ventricular Dysfunction

![Figure][1] ![Figure][1] [Video 1][2] Video 1 Transthoracic 2-dimensional electrocardiography of the patient in apical 4-chamber view by admission to the intensive care unit after surgery during circulatory depression with left ventricular dysfunction. Study is consistent with

In-line filtration minimizes organ dysfunction: new aspects from a prospective, randomized, controlled trial.

BackgroundInfused particles induce thrombogenesis, impair microcirculation and modulate immune response. We have previously shown in critically ill children, that particle-retentive in-line filtration reduced the overall complication rate of severe events, length of stay and duration of mechanical ventilation. We now evaluated the influence of in-line filtration on different organ function and thereby elucidated the potential underlying pathophysiological effects of particle infusion.MethodsIn this single-centre, prospective, randomized controlled trial 807 critically ill children were assigned to either control (n = 406) or filter group (n = 401), the latter receiving in-line filtration for complete infusion therapy. Both groups were compared regarding the differences of incidence rates and its 95% confidence interval (CI) of different organ dysfunction as defined by the International Pediatric Sepsis Consensus Conference 2005.ResultsThe incidence rates of respiratory (−5.06%; 95% CI, −9.52 to −0.59%), renal (−3.87%; 95% CI, −7.58 to −0.15%) and hematologic (−3.89%; 95% CI, −7.26 to −0.51%) dysfunction were decreased in the filter group. No difference was demonstrated for the occurrence rates of cardiovascular, hepatic, or neurologic dysfunction between both groups.ConclusionsIn-line filtration has beneficial effects on the preservation of hematologic, renal and respiratory function in critically ill patients. The presented clinical data further support our hypothesis regarding potential harmful effects of particles. In critically ill patients infused particles may lead to further deterioration of the microcirculation, induce a systemic hypercoagulability and inflammation with consecutive negative effects on organ function.Trial registrationClinicalTrials.gov number; NCT00209768

Systemic inflammatory response syndrome after pediatric congenital heart surgery: Incidence, risk factors, and clinical outcome

Systemic inflammatory response syndrome (SIRS) is frequent after cardiac surgery, but data on its incidence and perioperative risk factors are scarce for children with congenital heart disease.

Back to the roots? Dual cannulation strategy for ambulatory ECMO in adolescent lung transplant candidates: An alternative?

Bridging critically ill pediatric patients to lung transplantation still remains a major challenge. Although still controversial, within the last 5 years, ECMO has been increasingly used as a bridge to lung transplantation concept in adult and pediatric patients with acceptable outcomes. The outstanding developments in the field of extracorporeal devices and the introduction of awake ECMO concepts with the avoidance of mechanical ventilation have led to a real paradigm shift in the ICU management of pretransplant candidates with severe respiratory failure. Therefore, ECMO is no longer seen as a contraindication for lung transplantation at least at our center. Nevertheless, how to bridge these patients on ECMO still remains controversial. Thus, we introduced an ambulatory ECMO approach in adolescent lung transplant candidates with acute respiratory failure using a dual cannulation strategy and hereby present first results from this procedure.

Neonatal aortic arch thrombosis: analysis of thrombophilic risk factors and prognosis.

UNLABELLED Arterial thrombosis in neonates and children is a rare event and is often associated with external risk factors such as asphyxia or sepsis. We report our experiences with two neonates with spontaneous aortic arch thrombosis mimicking aortic coarctation. Despite single case reports until now, no data exist for the underlying thrombophilic risk factors and prognosis of this rare event. Both patients were carriers of a heterozygous factor V Leiden mutation, which has been reported once before as a risk factor for aortic arch thrombosis. One of our patients was operated upon successfully and is alive. The second patient suffered a large infarction of the right medial cerebral artery and had a thrombotic occlusion of the inferior caval vein. The patient obtained palliative care and died at the age of 6 days. In the literature, we identified 19 patients with neonatal aortic arch thrombosis. Of the 19 patients, 11 (58%) died. Including the two reported patients, the mortality rate of patients with multiple thromboses was 80% (8/10) compared with 18% (2/11) for patients with isolated aortic arch thrombosis; this difference reached statistical significance (p = 0.009). The analysis of thrombophilic disorders revealed that factor V Leiden mutation and protein C deficiency seem to be the most common risk factors for aortic arch thrombosis. CONCLUSION Neonatal aortic arch thrombosis is a very rare but life-threatening event, with a high rate of mortality, especially if additional thrombotic complications are present. Factor V Leiden mutation seems to be one important risk factor in the pathogenesis of this fatal disease.

Fulminant arterial thrombosis leading to amputation of forearm in a 16-year-old girl – Disastrous combination of diabetes mellitus, factor V Leiden mutation and oral contraception

Fulminant arterial thrombosis leading to amputation of forearm in a 16-year-old girl – Disastrous combination of diabetes mellitus, factor V Leiden mutation and oral contraception -

Rapid Regression of Classic Clinical Signs of Cyanosis Accompanied by Disappearing Major Aortopulmonary Collaterals After Surgical Palliation Only in a 6-Year-Old Girl With Tetralogy of Fallot

Tetralogy of Fallot is still the most common cyanotic heart defect and occurs in ≈1 in 3600 newborns or in 3.5% of the newborns with congenital heart disease.1,2 Since the first efforts of surgical repair in the 1950s, operation techniques with right ventricular outflow tract augmentation (RVOTA) and closure of ventricular septal defects have improved continuously. Today, in countries providing a high standard of medical care, patients with uncorrected tetralogy of Fallot presenting classic clinical signs of cyanosis are rare. A 6-year-old girl from Afghanistan with tetralogy of Fallot, a large malalignment ventricular septal defect, and high-grade infundibular pulmonary stenosis together with a hypoplastic pulmonary system had undergone a left-sided modified Blalock-Taussig shunt in her home country (exact date of surgery could not be determined). No further interventions were performed until the girl was transferred to Germany at 6 years of age. The clinical signs of chronic cyanosis at this time consisted of an extreme clubbing of the digits, especially of the toes, bluish skin, and a deep central cyanosis as indicated by blue lips and a cyanosed tongue (Figure 1A, 1D, and 1G). The oxygen saturation, measured transcutanously, was ≈65%. The hemoglobin level was 20 g/dL. Figure 1. Images …