The various clinical spectra of juvenile xanthogranuloma: imaging for two case reports and review of the literature.

BACKGROUND: Juvenile xanthogranuloma (JXG) belongs to the heterogeneous group of non-Langerhans cell histiocytosis and is caused by an accumulation and proliferation of macrophages. In the majority of cases JXG is a disorder of early childhood presenting during the first 2 years of life. The typical presentation is a solitary reddish or yellowish skin papule or nodule with spontaneous regression and no need for treatment. CASE PRESENTATION: Two infants with an atypical presentation of JXG, one with multiple blueberry muffin rash-like skin lesions and the other with severe multi-systemic involvement, are reported. Diagnosis was established by skin biopsy including histological work-up and immunostaining, where markers for macrophages (CD68 and CD163) exhibited significant reactivity. CONCLUSION: JXG is the most common of the non-Langerhans cell histiocytosis. The typical presentation is a solitary skin lesion. The purpose of this report is to familiarize paediatricians with an unusual variant of this entity in order to facilitate early diagnosis and raise awareness for possible visceral complications and associated medical conditions.

Case report of a central venous access device-associated thrombosis with aortic embolism in a preterm infant.

BACKGROUND: Thrombosis in neonates is commonly a central venous access device (CVAD) associated complication. Furthermore, a patent foramen ovale (PFO) is frequently seen in preterm infants. Even though a coincidence of both is not unusual, detaching of the thrombus and organisation of an aortic embolism has not been described until now. Treatment recommendations of CVAD-associated thrombosis in neonates do not consider frequently seen complications of preterm infants e.g. intraventricular haemorrhage. This is the first case of a very preterm infant with pre-existing intraventricular haemorrhage, who developed a CVAD-associated thrombosis and thromboembolic complications. CASE PRESENTATION: The authors report on a very preterm girl with a pre-existing intraventricular haemorrhage and a CVAD-associated thrombus that, after removal of the CVAD, led to assumed pulmonary embolism and to an extended aortic embolism with consequent cerebral stroke. The girl was treated with unfractionated heparin (UFH) for about 50 days. During the further in-hospital stay the girl developed a mild bronchopulmonary dysplasia. Follow-up revealed clinical signs of cerebral palsy. CONCLUSION: Even though preterm infants are often diagnosed with a PFO which constitutes the risk for paradoxical embolism, such complications do not occur frequently due to the physiological heart pressure proportion. Nevertheless, it is important to monitor vital parameters and cerebral perfusion after removing a CVAD with confirmed associated thrombosis, because thromboembolic complications are possible. If practicable, patients with a confirmed CVAD-associated thrombosis should be anticoagulated before removing the CVAD. However, in our patient it was rational to remove the CVAD without prior anticoagulation due to the pre-existing intraventricular haemorrhage. There are various treatment recommendations for thrombosis or embolism in infants. However, there are no clear recommendations in very preterm infants with a high risk of cerebral bleeding respectively a pre-existing intraventricular haemorrhage. We decided to treat our patient with unfractionated heparin until the affected vessels were recanalised. Finally, it remains a case-by-case decision how to treat CVAD-associated thrombosis and consequent embolism depending on the patient's medical history.

[New and future treatment approaches for allergic conjunctivitis]. / Neue und zukünftige Therapieansätze in der Behandlung der allergischen Konjunktivitis.

BACKGROUND: In severe and recurrent ocular allergies conventional ophthalmic drugs can reach their limits, especially in chronic forms. The first novel immunomodulators and biologicals are already in clinical use and could provide relief. OBJECTIVE: Based on the immunopathophysiological mechanisms of ocular allergies, possible targets for innovative treatment approaches are presented. An overview of promising new and future immunomodulators and biologicals and their modes of action is also given. MATERIAL AND METHODS: Current reviews on ocular allergies and the treatment of systemic allergic diseases were screened. Case reports on the treatment of ocular allergy using immunomodulators and biologicals were analyzed. The clinical relevance and possible applications are presented. RESULTS: In chronic forms of ocular allergies, complex ocular surface inflammatory responses mediated via immunoglobulin E (IgE), mast cells, CD4-positive type 2 T­helper cells and eosinophilic granulocytes are predominant. Cyclosporine A 0.1% eyedrops have been approved in Europe since 2018 for children aged 4 years and older with severe vernal keratoconjunctivitis (VKC). In addition, case reports present promising data on the systemic off-label use of biologicals, such as dupilumab or omalizumab, in refractory VKC or atopic keratoconjunctivitis (AKC). CONCLUSION: A profound understanding of the immunopathophysiology of ocular allergies is necessary to detect further targets for future immunomodulators and biologicals. Currently, immunomodulatory therapy remains limited to cyclosporine A eyedrops. Other immunomodulatory agents, such as tacrolimus and biologicals can only be used off-label. Further studies on the controlled clinical use of these substances in the treatment of VKC or AKC are underway.

Patent ductus arteriosus, low platelets, cyclooxygenase inhibitors, and intraventricular hemorrhage in very low birth weight preterm infants.

OBJECTIVE: To assess the risk for intraventricular hemorrhage (IVH) in very low birth weight preterm infants with patent ductus arteriosus (PDA) and low platelet count with treatment with cyclooxygenase (COX) inhibitors. STUDY DESIGN: Diagnosis and treatment of PDA, as well as risk factors for IVH, were assessed using prospectively collected data of all infants born at a gestational age <32 weeks and with a birth weight ≤ 1500 g at Innsbruck University Hospital (January 2003-December 2009). Infants with severe thrombocytopenia (<50 × 10(9)/L) were excluded from analysis. RESULTS: Sixty-five (20%) of the 325 infants had IVH, and 149 (45.9%) of the 325 were treated with COX inhibitors. Treatment of PDA with COX inhibitors was not an independent risk predictor for IVH in preterm infants with platelets ≥ 100 × 10(9)/L. However, COX inhibitors amplified the risk of bleeding in the presence of moderately decreased platelets (50-99 × 10(9)/L) on days of life 2-7. Multivariable OR for IVH were 0.89 [95% CI 0.43-1.87] for patients with platelets ≥ 100 × 10(9)/L and treatment with COX inhibitors, 3.40 [95% CI 1.13-10.29] for those with moderately decreased platelets without treatment, and 53.3 [95% CI 5.9-484] for patients with both moderately decreased platelets and COX inhibitor treatment compared with those with platelets ≥ 100 × 10(9)/L and no treatment (reference group) (P < .001). CONCLUSION: In very low birth weight infants with moderate thrombocytopenia treatment with COX inhibitors increased the risk for intracerebral bleeding. Any benefits of this therapy should be carefully balanced against this potential hazard.

[Corneal disease in childhood-Hereditary, degenerative or infectious?] / Hornhauterkrankungen im Kindesalter ­ Hereditär, degenerativ oder infektiös?

BACKGROUND: Adequate visual acuity significantly contributes to the age-appropriate development of children's neurobehavior. Infantile corneal opacities are rare but implicate a high potential for amblyopia. OBJECTIVE: This review aims to provide an overview of the most common causes of infantile corneal opacities and highlights ophthalmopathological correlations. METHODS: The following review is based on an extensive literature search. RESULTS: If metabolic diseases, traumatic or infectious events can be excluded as a cause for an infantile corneal opacity, it is important to focus on the 3Ds, corneal dysgenesis, corneal dystrophy or corneal degeneration. DISCUSSION: If corneal opacities occur in childhood, early recognition, diagnosis, and initiation of treatment, including prophylaxis of amblyopia, are of utmost importance. In unexplained corneal opacities the histopathological work-up of the explanted cornea can contribute to the final diagnosis.

Saving of Time Using a Software-Based versus a Manual Workflow for Toric Intraocular Lens Calculation and Implantation.

Background: To determine whether there is a significant saving of time when using a digital cataract workflow for digital data transfer compared to a manual approach of biometry assessment, data export, intraocular lens calculation, and surgery time. Methods: In total, 48 eyes of 24 patients were divided into two groups: 24 eyes were evaluated using a manual approach, whereas another 24 eyes underwent a full digital lens surgery workflow. The primary variables for comparison between both groups were the overall time as well as several time steps starting at optical biometry acquisition until the end of the surgical lens implantation. Other outcomes, such as toric intraocular lens misalignment, reduction of cylinder, surgically induced astigmatism, prediction error, and distance visual acuity were measured. Results: Overall, the total diagnostic and surgical time was reduced from 1364.1 ± 202.6 s in the manual group to 1125.8 ± 183.2 s in the digital group (p < 0.001). The complete time of surgery declined from 756.5 ± 82.3 s to 667.3 ± 56.3 (p < 0.0005). Compared to the manual approach of biometric data export and intraocular lens calculation (76.7 ± 12.3 s) as well as the manual export of the reference image to a portable external storage device (26.8 ± 5.5 s), a highly significant saving of time was achieved (p < 0.0001). Conclusions: Using a software-based digital approach to toric intraocular lens implantation is convenient, more efficient, and thus more economical than a manual workflow in surgery practice.

3D-printed heart models for hands-on training in pediatric cardiology - the future of modern learning and teaching?

Background: This project aims to develop a new concept in training pediatric cardiologists to meet the requirements of interventional cardiac catheterizations today in terms of complexity and importance. This newly developed hands-on training program is supposed to enable the acquisition of certain skills which are necessary when investigating and treating patients in a catheter laboratory. Methods: Based on anonymous CT-scans of pediatric patients' digital 3D heart models with or without cardiac defects were developed and printed three-dimensionally in a flexible material visible under X-ray. Hands-on training courses were offered using models of a healthy heart and the most common congenital heart defects (CHD). An evaluation was performed by quantifying fluoroscopy times (FL-time) and a questionnaire. Results: The acceptance of theoretical and practical contents within the hands-on training was very positive. It was demonstrated that it is possible to master various steps of a diagnostic procedure and an intervention as well as to practice and repeat them independently which significantly reduced FL-time. The participants stated that the hands-on training led to more confidence in interventions on real patients. Conclusion: With the development of a training module using 3D-printed heart models, basic and advanced training in the field of diagnostic cardiac examinations as well as interventional therapies of CHD is possible. The learning effect for both, practical skills and theoretical understanding, was significant which underlines the importance of integrating such hands-on trainings on 3D heart models in education and practical training.

Design and 3D printing of variant pediatric heart models for training based on a single patient scan.

BACKGROUND: 3D printed models of pediatric hearts with congenital heart disease have been proven helpful in simulation training of diagnostic and interventional catheterization. However, anatomically accurate 3D printed models are traditionally based on real scans of clinical patients requiring specific imaging techniques, i.e., CT or MRI. In small children both imaging technologies are rare as minimization of radiation and sedation is key. 3D sonography does not (yet) allow adequate imaging of the entire heart for 3D printing. Therefore, an alternative solution to create variant 3D printed heart models for teaching and hands-on training has been established. METHODS: In this study different methods utilizing image processing and computer aided design software have been established to overcome this shortage and to allow unlimited variations of 3D heart models based on single patient scans. Patient-specific models based on a CT or MRI image stack were digitally modified to alter the original shape and structure of the heart. Thereby, 3D hearts showing various pathologies were created. Training models were adapted to training level and aims of hands-on workshops, particularly for interventional cardiology. RESULTS: By changing the shape and structure of the original anatomy, various training models were created of which four examples are presented in this paper: 1. Design of perimembranous and muscular ventricular septal defect on a heart model with patent ductus arteriosus, 2. Series of heart models with atrial septal defect showing the long-term hemodynamic effect of the congenital heart defect on the right atrial and ventricular wall, 3. Implementation of simplified heart valves and addition of the myocardium to a right heart model with pulmonary valve stenosis, 4. Integration of a constructed 3D model of the aortic valve into a pulsatile left heart model with coarctation of the aorta. All presented models have been successfully utilized and evaluated in teaching or hands-on training courses. CONCLUSIONS: It has been demonstrated that non-patient-specific anatomical variants can be created by modifying existing patient-specific 3D heart models. This way, a range of pathologies can be modeled based on a single CT or MRI dataset. Benefits of designed 3D models for education and training purposes have been successfully applied in pediatric cardiology but can potentially be transferred to simulation training in other medical fields as well.

Rates of Hepatocellular Carcinoma After Start of Treatment for Chronic Hepatitis C Remain High with Direct Acting Antivirals: Analysis from a Swiss Liver Transplant Center.

BACKGROUND: Direct-acting antivirals (DAA) have revolutionized the therapy of chronic hepatitis C (CHC) and have replaced previous PEG-interferon/ribavirin (PEG-IFN/RBV) treatment. Patients with CHC and advanced liver disease are at increased risk for hepatocellular carcinoma (HCC). However, the effects of DAA-based CHC treatment on subsequent HCC incidence remain poorly understood. PATIENTS AND METHODS: This retrospective single-institution cohort study included 243 consecutive patients after PEG-IFN/RBV and 263 patients after DAA treatment. Multivariable cause-specific Cox proportional hazards models were used to compare time to HCC between treatment types, censoring patients who died or had an orthotopic liver transplantation (OLT) at the time of the competing event. Age, gender, BMI, viral load, cirrhosis, fibrosis stage, diabetes, virus genotype and previous PEG-IFN/RBV (before DAA) were used as covariates. In addition, we performed a propensity score-matched analysis. RESULTS: Nineteen HCC cases were observed after DAA therapy compared to 18 cases after PEG-IFN/RBV treatment. Patients were followed for a median of 4.1 years (IQR: 3.5-4.7) for DAA and 9.3 years (IQR: 6.6-12.4) for the PEG-IFN/RBV group. In an unadjusted Cox model, a hazard ratio (HR) of 6.40 (CI: 2.20-18.61, p=0.006) for HCC following DAA vs PEG-IFN/RBV was estimated. In multivariable Cox proportional hazard models, age and liver cirrhosis were identified as further HCC risk factors but the HR estimates for DAA vs PEG-IFN/RBV still indicate a considerably increased hazard associated with DAA treatment (HR between 7.23 and 11.52, p≤0.001, depending on covariates). A HR of 6.62 (CI: 2.01-21.84, p=0.002) for DAA vs PEG-IFN/RBV was estimated in the propensity score-matched analysis. The secondary outcomes death and OLT did not differ between treatment groups. CONCLUSION: In a cohort study from a tertiary care hospital rates of HCC after the start of DAA treatment were higher compared to PEG-IFN/RBV treatment. Our data reinforce the recommendation that surveillance should be continued after successful CHC treatment.

Prophylactic low-dose paracetamol administration associated with lowered rate of patent ductus arteriosus in preterm infants - Impact on outcome and pain perception.

BACKGROUND: To determine the rate of patent ductus arteriosus after prophylactic low-dose paracetamol administration, the impact on outcome parameters, possible treatment side-effects and the influence on pain perception. METHODS: We report retrospective single-centre outcome data of premature infants ≤ 32 weeks of gestation (n = 476). The intervention group received intravenous paracetamol, the control group obtained no preventive therapy. Ductal closure rate and outcome parameters were compared between the two groups. Adverse effects were determined by laboratory parameters. For the assessment of pain the Bernese Pain Scale for Neonates was used. RESULTS: The rate of patent ductus arteriosus was significantly lower in the paracetamol-treated group compared to the control group (13.6% vs. 38.2%, p < 0.001). With regard to secondary outcome parameters, severe and moderate bronchopulmonary dysplasia (2.7% vs. 7.4%, p = 0.023), severe retinopathy of prematurity (0% vs. 4.4%, p = 0.002) and late onset sepsis (2.7% vs. 8.3%, p = 0.009) were significantly less frequent in the paracetamol group. Except for a 1.5-fold increased risk for hyperbilirubinemia (86.0% vs. 77.6%, p = 0.035) in the paracetamol group following treatment, no significant differences in laboratory parameters were found. Relating to pain, the administration of Glucose 33% was significantly more often necessary in the control group compared to the paracetamol-treated group (mean 13.48 vs. 8.71, p < 0.001), just as the need for additional treatment with systemic analgesics, which was more frequent in the control group (mean 0.72 vs. 0.57, p = 0.361). CONCLUSION: In our study we were able to show a significantly lower rate of patent ductus arteriosus after prophylactic paracetamol administration without serious adverse effect, but a beneficial influence of this regime on the patient's pain perception.

EpCAM overexpression is associated with high-grade urothelial carcinoma in the renal pelvis.

BACKGROUND: EpCAM serves as an attractive target for immunotherapy due to its expression on the surface of most epithelial cancer cells. Urothelial carcinoma of the renal pelvis (RP-UC) comprises 2.4-4.6% of tumors of the lower urinary tract. To assess the expression of EpCAM in RP-UC a retrospective study was performed. PATIENTS AND METHODS: Tumor tissue from 42 patients with RP-UC was selected from the archives of the Institute of Pathology, Medical University of Innsbruck, Austria. EpCAM expression was demonstrated by immunohistochemistry using the mouse monoclonal antibody ESA. RESULTS: EpCAM overexpression was significantly associated with high grade and invasive behaviour (p = 0.014 and p = 0.029) and the presence of lymph node metastases (p = 0.031), but not with the extent of nodal involvement (p = 0.12). CONCLUSION: In RP-UC, EpCAM overexpression is associated with an aggressive tumor phenotype. The association of EpCAM overexpression with the presence of lymph node metastasis may be of prognostic and therapeutic relevance.

Connatal Urinary Ascites in a Female Preterm.

BACKGROUND: Connatal urinary ascites is rare in females without associated malformations and occurs following bladder rupture. CASE PRESENTATION: A female very preterm was delivered by caesarean section because of abnormal Doppler findings. The mother suffered from viral pneumonia requiring intensive care in the third trimester of pregnancy. Serial fetal ultrasound examinations showed a megacystis and ascites. Postnatally, pronounced isolated ascites was drained and its urinary nature was confirmed. The bladder leak was demonstrated when blue dye, instilled via a Foley catheter, appeared in the ascitic drain. After removal of the catheter spontaneous micturition was unremarkable. A micturating cystourethrogram showed spontaneous closure of the bladder leak. CONCLUSION: The female infant experienced fetal bladder rupture and connatal urinary ascites due to maternal pneumonia and intensive care. The use of blue dye is an effective alternative method to any contrast media radiography and should be considered, especially in very preterm infants.

Patient- and Family-Centered Care in the Preoperative Setting: Simulation Cases Featuring Standardized Patients for Anesthesia Residents.

INTRODUCTION: Evidence links patient-centered care to improvements in allocation of health care resources, patient satisfaction, chronic disease self-management, morbidity, and mortality. Support from families, too, can improve patients' health and well-being. However, patient- and family-centered care (PFCC) in the preoperative setting is challenging due to short-term relationships with patients, time constraints, and lack of training. METHODS: This module uses simulations with standardized patients. Groups of residents are divided into pairs, and each resident in a pair alternately participates in, or observes via live camera feed, a simulation case. The pair participates in both debriefing sessions. Two simulation cases are run. The first features a Jehovah's Witness who wants lifesaving blood but does not want her accompanying daughter to know. Despite excruciating pain, analgesia is being withheld because surgery consent has not been obtained. The second features a patient with HIV who does not want her accompanying pastor to know. The operating room nurse calls for a resident to bring her to surgery, but the patient wants to talk to her mother, who has yet to arrive. The purpose of the curriculum is for anesthesia residents to apply PFCC when having difficult preoperative conversations with patients and their families and obtaining anesthesia consent. RESULTS: Participants rated the training environment, faculty, debriefing, clinical application, and contribution of standardized patients highly. Participants' perceived self-efficacy for each core principle of PFCC improved postsimulation compared to presimulation. DISCUSSION: We believe this curriculum can contribute to improvement in PFCC and subsequent improvement in the quality and safety of health care.

Pasteurization of breastmilk decreases the rate of postnatally acquired cytomegalovirus infections, but shows a nonsignificant trend to an increased rate of necrotizing enterocolitis in very preterm infants--a preliminary study.

AIM: This study assessed whether feeding preterm infants unpasteurized breastmilk (1) decreases the rate of late-onset sepsis and necrotizing enterocolitis and (2) increases the rate of postnatally acquired cytomegalovirus infections. SUBJECTS AND METHODS: Between January 2008 and July 2013, preterm infants below 32 completed weeks of gestational age admitted to the neonatal intensive care unit of Innsbruck Medical University (Innsbruck, Austria) (n=344) were eligible for the study. Of those, 323 fed breastmilk were retrospectively enrolled in the study. Two groups were formed, with 164 infants being fed unpasteurized and 159 infants being fed pasteurized breastmilk. RESULTS: There was no significant difference in the rate of late-onset sepsis or necrotizing enterocolitis between the unpasteurized and pasteurized breastmilk groups (late-onset sepsis, 15.9% versus 15.1% [p=0.486]; necrotizing enterocolitis, 2.4% versus 4.4% [p=0.254]). The number of infants diagnosed with postnatally acquired cytomegalovirus infection was significantly higher in the unpasteurized group (39.3%) compared with the pasteurized group (4.2%) (p=0.008). CONCLUSIONS: Feeding preterm infants unpasteurized breastmilk increases the rate of postnatally acquired cytomegalovirus infections. However, we also demonstrate a nonsignificant trend to a decreased rate of necrotizing enterocolitis in the unpasteurized group, which needs to be confirmed in larger studies.

Severe cold agglutinin disease caused by recurrent monomorphic Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorder (PTLD), clonally related to an EBV-negative plasmacytic hyperplasia in a pediatric multivisceral organ transplant recipient.

PTLD represent major post-transplant complications. The major etiologic factor is EBV. Association with cold agglutinin disease has not been described so far. We report a three-yr-old girl who developed oligoclonal EBV-negative plasmacytic hyperplasia as well as Coombs test-positive anemia one yr after multivisceral organ transplantation, performed after subtotal bowel resection for colointestinal aganglionosis and liver cirrhosis resulting from long-term parenteral nutrition. The patient was treated for plasmacytic hyperplasia with cyclophosphamide and prednisolone and achieved clinical remission. One yr later PTLD progressed possibly driven by EBV to DLBCL. The migration patterns of the amplified Ig heavy chain genes demonstrated a probable clonal relationship of the DLBCL to a clone almost present in the plasmacytic hyperplasia. This progression was accompanied by a rapid rise of cold agglutinin titers with symptoms of severe cold agglutinin disease, leading to right femoral and extern iliac vein thromboses requiring partial leg amputation. After four cycles of rituximab, cyclophosphamide, and prednisolone, the patient achieved complete PTLD remission and the cold agglutinins disappeared. Summarizing, PTLD may be accompanied by cold agglutinin disease, and both may be successfully treated by immuno-chemotherapy. The appearance of cold agglutinins in transplant patients may indicate PTLD development.