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BackgroundThe majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year.MethodOver a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly.ResultsAt the end of the observation period, median age was 6.3 years (IQR: 2.8–11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p=0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss −1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, theABCA3sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function.ConclusionThe natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.

Introduction Pulmonary alveolar proteinosis (PAP) is defined by increased accumulation of surfactant in the alveolar space. PAP has been reported to be associated with a large number of clinical conditions and diseases. Whole lung lavages can be helpful to stabilize the clinical course of PAP until the underlying condition is identified, which may enable more specific treatment. Recently, heterozygous OAS1 gain-of-function variants were described as cause in a patient with infantile-onset PAP combined with hypogammaglobulinemia. Case presentation At age 4 months, a female infant born to term was diagnosed with hypogammaglobulinemia and treated with monthly immunoglobulin injections. At age 15 months, the girl needed supplemental oxygen at night, and at age 18 months, also during the day. At age 2 years, pulmonary alveolar proteinosis of unknown etiology was diagnosed by computed tomography scan and open lung biopsy. Subsequently, monthly whole lung lavages (WLLs) were started, which stabilized the clinical course for over 2 years until a disease-causing OAS1 variant was diagnosed and the patient was successfully treated by hematopoietic stem cell transplantation. Conclusion Here, we describe the successful management of a female patient with severe PAP caused by a heterozygous OAS1 gain-of-function variant until a definitive diagnosis was made and cured by hematopoietic stem cell transplantation. This article is protected by copyright. All rights reserved.

Tinnitus aurium is the conscious perception of an acoustic sensation in the absence of a corresponding external stimulus. Besides other psychological factors, psychodynamic factors play an importan...

BACKGROUND Persistent tachypnea of infancy (PTI) is the most common interstitial lung disease in young children. As no standardized therapeutic guidelines exist, different pharmaceuticals are used to treat PTI; inhaled corticosteroids (ICS) and bronchodilators being mostly used. This observation assessed the effectiveness of bronchodilators and ICS in children with PTI enrolled in the children's interstitial lung diseases (chILD)-EU Register. METHODS Symptomatic children with PTI were observed according to a predetermined stepwise protocol including bronchodilators as the first choice treatment (6 weeks). In patients with incomplete response, additionally, ICS was given (12 weeks). Signs, symptoms, and pulmonary function were evaluated at three time points: at baseline, 6 (±1) weeks after initiation of bronchodilators, and 12 (±1) weeks after bronchodilators/ICS. RESULTS Thirty-one children (median age: 44 months, interquartile range [IQR]: 15-67) were included. The therapy was associated with a significant reduction of tachypnea (53.3% of patients, p = 0.02), exercise intolerance (52.2% of patients, p

Zusammenfassung Hintergrund Der Psychosomatische Konsiliardienst bietet die Möglichkeit zur Korrektur von Fehldiagnosen. Die nicht-analytischen, erfahrungsbasierten Bauchgefühle des Arztes spielen dabei als diagnostische Wegbereiter eine wesentliche Rolle. Methodik In einer Fallserien-Studie wurden die Abläufe von 165 psychosomatischen Konsilen und die dabei im Konsiliarius auftretenden emotionalen und kognitiven Prozesse erfasst. Der diagnostische Prozess wurde unter Bezugnahme auf die duale Prozesstheorie analysiert. Beim Bauchgefühl wurde zwischen einem sense of alarm und einen sense of reassurance unterschieden. Exemplarisch wurden bei vier Konsilen die Prozesse dargestellt, die zur Aufdeckung von Fehldiagnosen führten. Ergebnisse In 24 Konsilen (16%) wurde eine Fehldiagnose festgestellt. Anlass hierfür war immer ein sense of alarm, der sich in 29 von 165 Konsilen (18%) einstellte. In 11 Konsilen (7%) bestand ein sense of reassurance, der in zehn Konsilen mit einer Bestätigung der Diagnose assoziiert war und nur in einem Fall einem sense of alarm wich und zu einer Diagnosekorrektur führte. Schlussfolgerungen Die Beachtung des Bauchgefühls und seines sense of alarm ist eine effektive Methode, Fehldiagnosen zu erkennen. Ausbildungsprogramme sollten nicht nur das rational-analytische Denken, sondern auch die selbstkritische Introspektionsfähigkeit des Arztes fördern.

BackgroundMonitoring disease progression in childhood interstitial lung diseases (chILD) is essential. No information for the minimal important difference (MID), which is defined as the smallest change in a parameter that is perceived as important prompting a clinician to change the treatment, is available. We calculated MIDs for vital signs (respiratory rate, peripheral oxygen saturation in room air, Fan severity score) and health-related quality of life (HrQoL) scores.MethodsThis study used data from the Kids Lung Register, which is a web-based management platform that collects data of rare paediatric lung disorders with a focus on chILD. Data of vital signs and HrQoL scores (Health Status Questionnaire, chILD-specific questionnaire and PedsQL V.4.0) were collected. MIDs were calculated according to distribution-based (one-third SD) and anchor-based methods (using forced expiratory volume in 1 s and forced vital capacity) as anchors.ResultsBaseline data of 774 children were used to calculate the following MIDs: respiratory rate 1.3 (z-score), O2saturation in room air 3.0%, Fan severity score 0.2–0.4, Health Status Questionnaire 0.4–0.8, chILD-specific questionnaire 4.4%–8.2%, physical health summary score 7.8%–8.9%, psychosocial health summary score 3.4%–6.9% and total score 5.1%–7.4%. Results of the responsiveness analysis generally agreed with the MIDs calculated.ConclusionsFor the first time, we provide estimates of MIDs for vital signs and HrQoL scores in a large cohort of chILD using different methods.

Objective Misdiagnoses are a major concern with far-reaching consequences, which have rarely been studied systematically. Therefore, the present study evaluated factors causing misdiagnoses identified by psychosomatic consultation services. Methods Over a period of 5 years, all patients referred to the psychosomatic consultation services of a large university hospital were analyzed consecutively for misdiagnoses. We analyzed the reasons for suspecting a misdiagnosis through systematic introspection during peer supervision and evaluated the causes during semistructured interviews with the referring physician. Results In 165 psychosomatic consultations, 24 disorders were misdiagnosed (15%). The reasons for questioning the initial diagnoses were the consulting physician's feelings and thoughts resulting from the patients' inappropriate behavior during the consultation and unusual clinical features. In eight cases, the misdiagnosis resulted from availability bias, and in three cases each it resulted from confirmation bias, search satisfaction bias, and framing effect and attribution bias. However, lack of medical knowledge played only a minor role. Conclusion This study highlights the nonrational elements of the diagnostic process. In the context of psychosomatic consultation services, introspection and intuitive thought processes are helpful in identifying misdiagnoses. Self-satisfaction (availability bias) and overconfidence (confirmation bias) are most likely to result in misdiagnoses.

Background Long segment laryngotracheoesophageal clefts (LTECs) are very rare large‐airway malformations. Over the last 40 years mortality rates declined substantially due to improved intensive care and surgical procedures. Nevertheless, long‐term morbidity, comorbidity, and clinical outcomes have rarely been assessed systematically. Methods In this retrospective case series, the clinical presentation, comorbidities, treatment, and clinical outcomes of all children with long‐segment LTEC that were seen at our department in the last 15 years were collected and analyzed systematically. Results Nine children were diagnosed with long segment LTEC (four children with LTEC type III and five patients with LTEC type IV). All children had additional tracheobronchial, gastrointestinal, or cardiac malformations. Tracheostomy for long‐time ventilation and jejunostomy for adequate nutrition was necessary in all cases. During follow‐up one child died from multiorgan failure due to sepsis at the age of 43 days. The clinical course of the other eight children (median follow‐up time 5.2 years) was stable. Relapses of the cleft, recurrent aspirations, and respiratory tract infections led to repeated hospital admissions. Conclusions Long‐segment LTECs are consistently associated with additional malformations, which substantially influence long‐term morbidity. For optimal management, a multidisciplinary approach is essential.

Background: Pulmonary alveolar proteinosis (PAP) is a heterogeneous condition with more than 100 different underlying disorders that need to be differentiated to target therapeutic options, which are generally limited. Methods: The clinical course of two brothers with pathogenic variants in the methionyl-tRNA synthetase (MARS)1 gene was compared to previously published patients. Functional studies in patient-derived fibroblasts were performed and therapeutic options evaluated. Results: The younger brother was diagnosed with PAP at the age of 1 year. Exome sequencing revealed the homozygous MARS1 variant p.(Arg598Cys), leading to interstitial lung and liver disease (ILLD). At 2 years of age, following surgery hypoglycemia was detected, the pulmonary condition deteriorated, and the patient developed multiorgan failure. Six therapeutic whole lung lavages (WLL) were necessary to improve respiratory insufficiency. Methionine supplementation was started and a high protein diet ensured, leading to complete respiratory recovery. The older brother, homozygous for the same MARS1 variant, had a long-known distinct eating preference of methionine-rich food and showed a less severe clinical phenotype. Decreased aminoacylation activity confirmed the pathogenicity of p.(Arg598Cys) in vitro. In agreement with our review of currently published ILLD patients, the presence of hepatopathy, developmental delay, muscular hypotonia, and anemia support the multisystemic character of the disease. Conclusions: Catabolic events can provoke a severe deterioration of the pulmonary situation in ILLD with a need for repetitive WLL. Although the precise role of oral methionine supplementation and high protein intake are unknown, we observed an apparent treatment benefit, which needs to be evaluated systematically in controlled trials.

ZusammenfassungDie Ösophagusatresie (ÖA) ist eine angeborene Kontinuitätsunterbrechung der Speiseröhre mit oder ohne Fistel zur Trachea (Tracheoösophageale Fistel, TÖF). Je nach Abstand zwischen den beiden Ösophagusenden unterscheidet man eine „kurzstreckige“ von einer „langstreckigen“ Form. Bis zu 50% der Neugeborenen weisen weitere Anomalien auf. Eine pränatale Diagnose der ÖA gelingt in 32–63% der Fälle. Die interdisziplinäre Betreuung dieser Kinder hat sich in den letzten Jahren gewandelt. In der folgenden Arbeit wird die aktuelle S2K-Leitlinie der Deutschen Gesellschaft für Kinderchirurgie zur Behandlung der ÖA mit unterer TÖF, die etwa 90% aller Fälle ausmacht, zusammengefasst. Hierzu gehören das präoperative Management sowie operative und anästhesiologische Aspekte (u. a. Thorakoskopie vs. Thorakotomie, präoperative Tracheobronchoskopie, intraoperative Hyperkapnie und Azidose). Ferner wird das postoperative Management insbesondere von relevanten Komplikationen wie der Anastomosenstenose beschrieben. Trotz Fortschritten in der Behandlung der ÖA ist die Langzeitmorbidität mit Motilitätsstörungen des Ösophagus, gastroösophagealer Refluxkrankheit, rezidivierenden Infektionen der oberen und unteren Atemwege, Tracheomalazie, mangelhaftem Gedeihen sowie orthopädischen Problemen nach Thorakotomie weiterhin hoch. Zum Erreichen einer guten Lebensqualität ist daher eine gute interdisziplinäre Nachsorge wichtig.

Background Social exclusion (ostracism) can lead to interactional frustration and may play an important role as trigger and symptom amplifier in affective disorders. To investigate immediate emotional and behavioral reactions as well as coping, social exclusion can be mimicked in experimental situations, e.g. in the Cyberball paradigm, a virtual ball tossing game which is well established in social psychology. The present cross-diagnostic study compares the responses to social exclusion in patients with chronic depression (CD), episodic depression (ED) and borderline personality disorder (BPD) in comparison to a healthy control group. Methods After baseline characterization, 120 participants (29 patients with CD, 20 with ED, 28 with BPD and 43 healthy controls) played Cyberball with two virtual players and complete exclusion after three times receiving the ball. Thereafter, standard questionnaires were applied for measuring needs, threats, inner tension, emotions and behavioral intentions. Results Patients with CD showed a higher intensity of ostracism and aversive impact, as well as the wish to escape the situation (behavioral intention) compared to ED. In most categories, CD and ED had scores between BPD and healthy controls (with this sequence) and with BPD patients showing the largest difference to healthy controls. Limitations The assessment did neither include objective behavioral measures (which is a general limitation in the majority of studies using Cyberball) nor any biological variables. The sample sizes of the diagnostic subgroups were moderate. Conclusions These findings support the hypothesis that social exclusion situations lead to a more aversive emotional and behavioral reaction in CD compared to ED. Psychological and biological underpinnings of these reactions should be addressed in future transdiagnostic studies. Moreover, psychotherapy in CD should focus on specific needs of CD patients for developing a functional coping in threatening interpersonal situations.

Background Balanced composition of a well-functioning pulmonary surfactant is crucial and essential for normal breathing. Here, we explored whether the composition of lipids recovered by broncho-alveolar lavage (BAL) in children with cystic fibrosis (CF) differ from children with protracted bacterial bronchitis (PBB) and controls. We wanted to differentiate, if alterations are primarily caused by the disease process or secondary due to an increased amount of cell-membrane lipids derived from inflammatory cells. Methods Comprehensive lipidomics profiles of BAL fluid from children diagnosed with CF, PBB and controls were generated by electrospray ionization tandem mass spectrometry analysis. BAL cell differential and numbers were examined. Results 55 children (37 patients with CF, 8 children with PBB and 10 controls) were included in this study. Results showed comparable total quantities of lipids in all groups. Phospholipids were the major lipid fraction and similar in all groups, whereas the fractions of cholesteryl esters were less and of free cholesterol were increased in children with CF. Among the phospholipids, patients with CF had higher proportion of the non-surfactant membrane-lipids in the classes phosphatidylethanolamine based plasmalogens (PE P), phosphatidylethanolmine (PE) and phosphatidylserine (PS), but a lower proportion of phosphatidylcholine (PC) compared to healthy controls. No such changes were identified in the BAL fluid of children diagnosed with PBB. No differences were observed for the surfactant lipids dipalmitoyl-phosphatidylcholin (PC 32:0) and phosphatidylglycerol (PG). Conclusions In CF patients with neutrophilic airway inflammation the lipid composition for surfactant phospholipid components were unchanged, whereas alteration in lipid profile were characteristic for those found in membranes of inflammatory cells. We suspect that the changes in CF were caused by the prolonged inflammation in contrast to a relatively short standing process in PBB.

A psychosomatic consultation service offers an opportunity to correct misdiagnoses. The doctor's non-analytical, experience-based gut feeling plays an essential role as diagnostic trailblazer.In a case series study, the procedures of 165 psychosomatic consultations and the emotional and cognitive processes occurring in the consultant were recorded. The diagnostic process was analysed with reference to the dual process theory. With gut feeling, a distinction was made between a sense of alarm and a sense of reassurance. As an example, the processes that led to the discovery of misdiagnoses were presented at four consultations.A misdiagnosis was found in 24 consultations (16%). The reason for this was always a sense of alarm, which appeared in 29 of 165 consultations (18%). In 11 consultations (7%) there was a sense of reassurance, which in ten consultations was associated with a confirmation of the diagnosis and only in one case gave way to a sense of alarm and led to a later correction of the diagnosis.Paying attention to gut feeling and its sense of alarm is an effective method of recognizing misdiagnosis. Training programs should not only promote rational-analytical thinking, but also the doctor's self-critical introspection skills.Der Psychosomatische Konsiliardienst bietet die Möglichkeit zur Korrektur von Fehldiagnosen. Die nicht-analytischen, erfahrungsbasierten Bauchgefühle des Arztes spielen dabei als diagnostische Wegbereiter eine wesentliche Rolle.In einer Fallserien-Studie wurden die Abläufe von 165 psychosomatischen Konsilen und die dabei im Konsiliarius auftretenden emotionalen und kognitiven Prozesse erfasst. Der diagnostische Prozess wurde unter Bezugnahme auf die duale Prozesstheorie analysiert. Beim Bauchgefühl wurde zwischen einem sense of alarm und einen sense of reassurance unterschieden. Exemplarisch wurden bei vier Konsilen die Prozesse dargestellt, die zur Aufdeckung von Fehldiagnosen führten.In 24 Konsilen (16%) wurde eine Fehldiagnose festgestellt. Anlass hierfür war immer ein sense of alarm, der sich in 29 von 165 Konsilen (18%) einstellte. In 11 Konsilen (7%) bestand ein sense of reassurance, der in zehn Konsilen mit einer Bestätigung der Diagnose assoziiert war und nur in einem Fall einem sense of alarm wich und zu einer Diagnosekorrektur führte.Die Beachtung des Bauchgefühls und seines sense of alarm ist eine effektive Methode, Fehldiagnosen zu erkennen. Ausbildungsprogramme sollten nicht nur das rational-analytische Denken, sondern auch die selbstkritische Introspektionsfähigkeit des Arztes fördern.

Interstitial lung diseases in children (chILD) are rare and diverse. The current classifications include a group of early onset chILD specific to infancy, namely neuro-endocrine cell hyperplasia of infancy (NEHI), pulmonary interstitial glycogenosis (PIG) and the alveolar capillary-congenital acinar dysplasia (ACD-CAD) spectrum, as well as alveolar growth disorders. NEHI and PIG cells are seen in the normal developing foetal lung. We hypothesise that these conditions are in fact overlapping manifestations of pulmonary dysmaturity, respectively of airway, mesenchymal and vascular elements, rather than discrete clinical conditions in their own right. Clinically, these present as respiratory distress in early life. Mild cases rightly never undergo lung biopsy, and for these the clinical description 'persistent tachypnoea of infancy' has been proposed. In terms of pathology, we reviewed current literature, which showed that NEHI cells decline with age, and are not specific to NEHI, which we confirmed by unpublished re-analysis of a second dataset. Furthermore, specific genetic disorders which affect pulmonary maturation lead to a histological picture indistinguishable from NEHI. PIG and ACD-CAD are also associated with pulmonary growth disorders, and manifestations of PIG and NEHI may be present in the same child. We conclude that, contrary to current classifications, NEHI, PIG, and ACD-CAD should be considered as overlapping manifestations of pulmonary dysmaturation, frequently associated with disorders of alveolar growth, rather than as separate conditions. Identification of one of these patterns should be the start, not the end of the diagnostic journey, and underlying in particular genetic causes should be sought.

Introduction Hypersensitivity pneumonitis (HP) in children is a severe interstitial lung disease and potentially, a chronic condition, if not treated appropriately. No evidence-based guidelines are available; in particular, the role of systemic glucocorticoid therapy is unclear. Methods The aim of this randomized, double-blind, placebo-controlled, parallel-group, multi-center, phase II trial in pediatric HP was to assess the outcome of HP in children after 6 months of treatment and to compare 3 months of treatment with oral prednisolone or placebo. Results After 1.5 years and the inclusion of only four children, we terminated the study prematurely. Two of the children randomized to prednisolone did not achieve the predefined response of FVC to normal. One child treated with placebo recovered to normal, similar to another child treated with prednisolone. All children treated with steroids developed drug-related side effects. Discussion This uncompleted study illustrates the urgent medical need for evidence-based treatment protocols for this condition. We discuss the hurdles which were specific for completion of this trial in a rare condition. Among other options, we suggest the inclusion of children into an all-age study of HP, as in adults the same questions are unanswered.

Background Persistent tachypnea of infancy (PTI) is a rare pediatric lung disease of unknown origin. The diagnosis can be made by clinical presentation and chest high resolution computed tomography after exclusion of other causes. Clinical courses beyond infancy have rarely been assessed. Methods Patients included in the Kids Lung Register diagnosed with PTI as infants and now older than 5 years were identified. Initial presentation, extrapulmonary comorbidities, spirometry and clinical outcome were analyzed. Results Thirty-five children older than 5 years with PTI diagnosed as infants were analyzed. At the age of 5 years, 74% of the patients were reported as asymptomatic and did not develope new symptoms during the observational period at school-age (mean, 3.9 years; range, 0.3-6.3). At the age of about 10 years, none of the symptomatic children had abnormal oxygen saturation during sleep or exercise anymore. Lung function tests and breathing frequency were within normal values throughout the entire observational period. Conclusions PTI is a pulmonary disease that can lead to respiratory insufficiency in infancy. As at school age most of the previously chronically affected children became asymptomatic and did not develop new symptoms. We conclude that the overall clinical course is favorable.

Introduction: chILD comprises various rare respiratory conditions and partially overlaps with adult ILD. Lung fibrosis is the most common disease entity in adults; however, there are no data on the prevalence, clinical, radiological and histopathological presentation of pulmonary fibrosis in chILD. Aim: To assess the prevalence of fibrosis in lung biopsies from the international management platform, the European chILD registry (NCT02852928), and to correlate paediatric lung fibrosis with radiological findings. Methods: Features of fibrosis in biopsies were defined by the presence of any of the following: description of interstitial fibrosis, fibroblastic foci or honeycombing. A histological diagnosis of chronic pneumonitis of infancy (CPI) was also included. Fibrosis by chest computed tomography (CT) scans was defined by the presence of linear or reticular opacities, honeycombing, traction bronchiectasis or architectural distortion. Results: Lung biopsies were available for 149/825 chILD cases (18%); 46 biopsies (31%) had features of fibrosis and 11 were identified by CPI pattern alone. Mean age at biopsy was 6.4 years (range 0–26). Thirty cases were related to alveolar surfactant region (ABCA3: n=11; SFTPC: n=3), five to systemic disease processes (e.g. connective tissue disease: n=2) and three to immunodeficiency. Individual cases accounted for the other categories. Only 21/46 cases (46%) with biopsy-proven features of fibrosis had fibrosis features by CT. Conclusions: Features of fibrosis were already present in 31% of cases with a diagnostic lung biopsy. Concordance between biopsy- and CT-diagnosed fibrosis was lower than expected and requires further evaluation.

Esophageal atresia (EA) is a congenital anomaly that entails an interrupted esophagus with or without tracheoesophageal fistula (TEF). Depending on the distance of the two esophageal pouches a "short-gap" is distinguished from a "long-gap" variant. Up to 50% of newborns have additional anomalies. EA is prenatally diagnosed in 32-63% of cases. Recently, the interdisciplinary care in these children underwent substantial changes. Therefore, we summarize the current guideline of the German society of pediatric surgery for the treatment of patients with EA and distal TEF (Gross Type C). Controversies regarding the perioperative management include surgical-technical aspects, such as the thoracoscopic approach to EA, as well as general anesthesia (preoperative tracheobronchoscopy, intraoperative hypercapnia and acidosis). Moreover, postoperative complications and their management like anastomotic stricture are outlined. Despite significant improvements in the treatment of EA, there is still a relevant amount of long-term morbidity after surgical correction. This includes dysmotility of the esophagus, gastroesophageal reflux disease, recurrent respiratory infections, tracheomalacia, failure to thrive, and orthopedic complications following thoracotomy in the neonatal age. Therefore, close follow-up is mandatory to attain optimal quality of life.Die Ösophagusatresie (ÖA) ist eine angeborene Kontinuitätsunterbrechung der Speiseröhre mit oder ohne Fistel zur Trachea (Tracheoösophageale Fistel, TÖF). Je nach Abstand zwischen den beiden Ösophagusenden unterscheidet man eine „kurzstreckige“ von einer „langstreckigen“ Form. Bis zu 50% der Neugeborenen weisen weitere Anomalien auf. Eine pränatale Diagnose der ÖA gelingt in 32–63% der Fälle. Die interdisziplinäre Betreuung dieser Kinder hat sich in den letzten Jahren gewandelt. In der folgenden Arbeit wird die aktuelle S2K-Leitlinie der Deutschen Gesellschaft für Kinderchirurgie zur Behandlung der ÖA mit unterer TÖF, die etwa 90% aller Fälle ausmacht, zusammengefasst. Hierzu gehören das präoperative Management sowie operative und anästhesiologische Aspekte (u. a. Thorakoskopie vs. Thorakotomie, präoperative Tracheobronchoskopie, intraoperative Hyperkapnie und Azidose). Ferner wird das postoperative Management insbesondere von relevanten Komplikationen wie der Anastomosenstenose beschrieben. Trotz Fortschritten in der Behandlung der ÖA ist die Langzeitmorbidität mit Motilitätsstörungen des Ösophagus, gastroösophagealer Refluxkrankheit, rezidivierenden Infektionen der oberen und unteren Atemwege, Tracheomalazie, mangelhaftem Gedeihen sowie orthopädischen Problemen nach Thorakotomie weiterhin hoch. Zum Erreichen einer guten Lebensqualität ist daher eine gute interdisziplinäre Nachsorge wichtig.

Background Interstitial lung diseases in children (chILD) are rare and consist of many different entities that affect the parenchyma of the lungs, leading to a chronic lung disease. The natural course of many of these diseases is connected with a high morbidity and significant mortality. Symptomatic treatment consists of oxygen supplementation, adequate nutrition adapted to the high energy demand generated by the disease due to the increased breathing effort required, as well as immunization against respiratory pathogens to prevent exacerbations through respiratory infections. No proven pharmacological treatments are available to date. This placebo-controlled study aims to evaluate the efficacy and safety of the mid-term use of hydroxychloroquine in chILD. Methods and design The study is an explorative, prospective, randomized, double-blind, placebo-controlled investigation of hydroxychloroquine (HCQ) in chILD. Patients can be included into the trial when diagnosed with a chronic (≥ 3 weeks’ duration) diffuse parenchymal lung disease (chILD) (1) genetically defined, (2) histologically defined or (3) diagnosed with idiopathic pulmonary hemorrhage (hemosiderosis). The study contains of two different study blocks, a START and a STOP block, which can be initiated in any sequence. Each patient can participate in each block only once. In the START block subjects are randomized to parallel groups for 4 weeks treatment, then the placebo group is switched to the active drug. In the STOP block, subjects taking HCQ are randomized into parallel groups treated with placebo or HCQ. Discussion This study is the first international, investigator-initiated, prospective and controlled investigation of a pharmacological treatment in chILD. The block design was selected as it has the advantage of accommodating patients who are initiating or withdrawing from HCQ therapy, thus allowing the participation of those who were previously started on off-label HCQ. The cross-over design and selected outcome parameters enables us to include appropriate numbers of patients of all age groups from neonates to adults suffering from these rare diseases. Trial registration This is an exploratory, Phase 2a, randomized, double-blind, placebo-controlled, parallel-group, multinational study investigating the initiation or withdrawal of hydroxychloroquine in subjects with chILD. Study title: Hydroxychloroquine in pediatric ILD: START randomized controlled in parallel groups, then switch placebo to the active drug, and STOP randomized controlled in parallel groups to evaluate the efficacy and safety of hydroxychloroquine (HCQ). Short title: HCQ in pediatric ILD, particularly 4surfdefect. EudraCT, ID: 2013–003714-40. Registered on 2 July 2013. ClinicalTrials.gov, ID: NCT02615938 . Registered on 8 November 2015. IZKS trial code: 2013–006; Sponsor: University Hospital, Ludwig-Maximilians University of Munich. Responsible Party: Prof. Dr. med. Matthias Griese, University Hospital, Ludwig-Maximilians University of Munich, Germany.

Background The experience of social exclusion (ostracism) is linked to the etiology and maintenance of depression. Most individuals experience emotional stress in states of social exclusion. Insecurely attached individuals, especially with an unresolved trauma, show maladaptive coping in response to social stress. The present study examines (a) the differences with regards to attachment representations in episodic (ED) and chronic depressive (CD) inpatients and (b) how ostracism affects their emotional reactions. Methods Patients with CD (n=29) and ED (n=23) and healthy control subjects (n=29) were interviewed using the Adult Attachment Projective Picture System (AAP), a valid measure to assess attachment representation; and played a virtual ball tossing game simulating social exclusion (Cyberball). Multiple depression-related risk and protective factors were considered. We hypothesized that CD patients show the most severe attachment disorganization and are emotionally most affected by the social exclusion situation. Moreover, we explored the interaction between ostracism and attachment. Results Contradicting our hypotheses, ED and CD individuals were almost akin with regards to their attachment insecurity/disorganization and reactions to Cyberball. An emotionally altered reaction to social exclusion was identified in the insecure-disorganized depressive subgroup. Limitations Small sample size hampering further subgroup analyses. The ED sample may include single CD subjects with recent manifestation. Conclusions The pattern of emotion regulation in the depressive groups matches with findings from clinical studies, including attachment research. The relationship between attachment representations and ostracism should be further investigated in larger samples of depressive individuals.

Background: Genetic pulmonary alveolar proteinosis (PAP) is a term describing inborn diseases with abundant surfactant accumulation in the lungs. The determination of the molecular cause is critical to make the correct therapy decisions Recently three families with PAP due to mutations in OAS1 gene have been described. Here we present another case of this novel disease. Case Presentation: At 4 months of age a term-born female presented with recurrent severe respiratory and gastrointestinal tract infections. Hypogammaglobulinaemia was noted, but no immune-deficiency could be diagnosed. She was treated with monthly immunoglobulins. Over time the clinical course deteriorated; at age of 12 months the girl needed supplemental oxygen during night times and at 18 months also during daytime. The diagnosis of a pulmonary alveolar proteinosis (PAP) of unknown cause was made by CT scan and open lung biopsy. Whole lung lavages (WLL) were started at 2 years of age every 4 weeks. Whole exome sequencing identified a new de novo heterozygous mutation in OAS1. With this the diagnosis the patient was prepared for allogeneic haematopoietic stem cell transplantation (HSCT) with a matched unrelated donor, which was performed at the age of 4 years. During the first few days following HSCT oxygen demand increased, making another WLL necessary. Then the pulmonary clinical course rapidly improved day by day until normalizing of gas exchange at day 15. Conclusion: WLL in patients with pulmonary alveolar proteinosis can stabilize patients until a definitive diagnosis can be made. Bone marrow transplantation may cure PAP due to a mutation in the OAS1 gene.

Background: Pulmonary interstitial glycogenosis (PIG) is a rare interstitial lung disease in children. The clinical hallmark is a rapid onset with respiratory distress and hypoxemia shortly after birth in the absence of an infectious cause or a surfactant dysfunction syndrome. The diagnosis can only be made by lung biopsy. The histopathological pattern defining PIG can exist in diffuse or patchy distribution. Only few cases have been reported. Not much is known on clinical features, outcomes, CT imaging and histopathology. Methods: The clinical course, CT-scans and tissue samples of children diagnosed with PIG were collected and systematically re-analysed by clinicians, radiologists and pathologists all specialized in interstitial lung diseases in children. All data were uploaded into the Kidslungregister for follow up. Results: 11 children diagnosed with PIG were included in this study. All presented with respiratory distress shortly after birth. More than half of the children were diagnosed with additional abnormalities, especially congenital heart defects. The CT-scan of the lungs showed mainly groundglass opacities, consolidations and septal thickening. Of interest each tissue sample had signs of reduced alveolarization. The prognosis was favourable in almost all cases. When systemic glucocorticosteroids were given a fast improvement was noticed. Conclusion: PIG is a interstitial lung disease in infants with mostly favourable outcome. As alveolar growth retardation was present in all subjects this can support a theory of an underlying maturation delay. In all infants with congenital heart defects and unexplained respiratory distress an interstitial lung disease due to PIG should be considered.

BACKGROUND: Pulmonary interstitial glycogenosis (PIG) is a rare paediatric interstitial lung disease of unknown cause. The diagnosis can only be made by lung biopsy. Less than 100 cases have been reported. Clinical features, treatment and outcomes have rarely been assessed systematically in decent cohorts of patients.METHODS: In this retrospective multicentre study, the clinical presentation, radiologic findings, pattern of lung biopsy, extrapulmonary comorbidities, treatment and outcome of eleven children with PIG were collected systematically.RESULTS: 10/11 children presented with respiratory distress immediatly after birth and 8/11 needed invasive ventilation. In 8/11 children extrapulmonary comorbidities were present, congenital heart defects being the most common. 7/11 children received systemic glucocorticoids and of these four showed a clear favorable response. During a median follow-up of 3.0 years (range 0.42-12.0) one child died, while 10 patients improved. Chest CT-scans showed ground-glass opacities (7/10), consolidations (6/10), linear opacities (5/10) and mosaic attenuation (4/10) without uniform pattern. Besides interstitial thickening related to undifferentiated glycogen positive mesenchymal cells all tissue samples showed growth abnormalities with reduced alveolarization.CONCLUSIONS: PIG is associated with alveolar growth abnormalities and has to be considered in all newborns with unexplained respiratory distress. Apparent treatment benefit of glucocorticosteroids needs to be evaluated systematically.

Introduction: Children’s interstitial lung disease (chILD) comprises a heterogeneous group of over 200 different entities of diffuse lung diseases with symptom onset in childhood. Only 1-3 of one million children are affected per year. No evidence based treatment guidelines exist. Aim: First analysis of the distribution of chILD disease entities using a classification system also including cases without lung biopsy (Orphanet J Rare Dis 2015 10:122), as well as respiratory medications prescribed. Methods: Patients with chILD reported to the European Management Platform for Childhood Interstitial Lung Diseases between December 2012 and November 2016 were included. Baseline and follow up visits including information on disease course and respiratory treatments used in the whole cohort and specific subcategories were analysed. Results: 366 peer-reviewed patients received a final diagnosis: the most common was chILD related to alveolar surfactant region (category A4, n=194), followed by chILD related to systemic disease (B1, n=60), specific conditions of undefined etiology (A3, n=59) and chILD of the immune intact host (B2, n=46). The most commonly used drugs at baseline were glucocorticosteroids in 175 cases (48%), especially in the subcategories A4 and B1. Azithromycin was used in 24% and hydroxychloroquine in 14%. Conclusion: The knowledge of most frequently diagnosed subcategories of chILD and most commonly used medication in these groups will inform controlled studies in the future, especially for glucocorticosteroids and azithromycin in the subcategories A4 and B1.