Non-small cell lung carcinoma in an adolescent manifested by acute paraplegia due to spinal metastases: a case report

<p>Abstract</p> <p>Introduction</p> <p>Bronchial carcinomas in childhood and adolescence are extremely rare; only individual cases have been reported previously.</p> <p>Case presentation</p> <p>We report on a 16-year-old Caucasian German boy with non-small cell lung carcinoma (squamous cell non-small cell lung carcinoma) stage IV, T4N2M1, without epidermal growth factor receptor overexpression and/or mutation or k-ras mutation. He presented with paraplegia due to spinal metastases of the bronchial carcinoma. No familial predisposition or toxin exposure was identified. Treatment following adult protocols consisted of surgical intervention for spinal metastases, first-line cisplatinum and gemcitabine, irradiation and second-line docetaxel. After a transient response our patient experienced disease progression and died about 10 months later.</p> <p>Conclusion</p> <p>Response and survival in our 16-year-old patient were similar to adult patients with stage IV non-small cell lung carcinoma.</p

Analysis of lung function of 26 patients with congenital diaphragmatic hernia and evaluation of prognostic indicators for pulmonary morbidity

Die kongenitale Zwerchfellhernie (CDH- congenital diaphragmatic hernia) ist eine angeborene Fehlbildung des Zwerchfells mit Prolaps von Abdominalorganen in den Thorax. Das Krankheitsbild wird durch die Lungenhypoplasie und oftmals durch eine pulmonale Hypertonie kompliziert. Auch nach erfolgreicher Operation benötigen die Kinder häufig eine prolongierte Atemunterstützung. Patienten und Methoden: Der Krankheitsverlauf von 26 zwischen 1993 und 2003 in der Klinik für Neonatologie der Charité Campus Mitte behandelten Kindern mit einer CDH wurde retrospektiv erhoben. Außerdem wurden die im Alter von 32 Tagen (Median) mittels Bodyplethysmographie, Ruheatmungsanalyse und Okklusionstechnik bestimmten Atemfunktionsparameter ausgewertet. Anhand dieser Daten wurden prognostische Parameter für die pulmonale Morbidität evaluiert. Ergebnisse: Die Mehrzahl der CDH-Patienten hatte eine beeinträchtige Lungenfunktion, die Parameter der Atemfunktionsdiagnostik (AFD) - respiratorische Compliance und Resistance, das thorakale Gasvolumen, Atemfrequenz und Atemzugvolumen - unterschieden sich signifikant von den Werten einer pulmonal gesunden Kontrollgruppe. Die Datenanalyse zeigte Zusammenhänge zwischen Beatmungsdauer und -intensität (Beatmungsdrücke und Sauerstoffkonzentrationen) und einer pathologischen Lungenfunktion. Weiterhin trat bei früher pränataler Diagnose, nicht-linksseitiger Zwerchfellhernie, Patchverschluss, sowie den Komplikationen pulmonale Hypertonie und Pleuraerguss signifikant häufiger eine Ventilationsstörung auf. Bei pathologischem AFD-Ergebnis wiederum waren die Kinder länger hospitalisiert, insbesondere die Patienten mit kombiniert obstruktiv-restriktiver Ventilationsstörung. Conclusio: Auch nach erfolgreicher Operation einer CDH besteht bei vielen Patienten eine pathologische Lungenfunktion. Bei Vorliegen bestimmter Risikofaktoren ist die Wahrscheinlichkeit erhöht, eine Ventilationsstörung zu entwickeln. Dies unterstreicht die Notwendigkeit einer vorsichtigen Beatmungsstrategie, um zusätzliche Schädigungen durch Barotrauma und Sauerstofftoxizität zu minimieren. Es erscheint sinnvoll, alle Kinder mit CDH frühzeitig – klinische Stabilität vorausgesetzt - atemfunktionsdiagnostisch zu untersuchen und bei pathologischem Befund in eine engmaschige pulmonologische Weiterbetreuung zu überführen.Congenital diaphragmatic hernia (CDH) is a rare birth defect characterized by malformation of the diaphragm and prolapse of abdominal organs into the thoracic cavity. Complicating factors are pulmonary hypoplasia and pulmonary hypertension. Even after a successful operation, these patients commonly need prolonged assisted ventilation. Patients and Methods: We evaluated retrospectively the course of disease of 26 newborns with CDH, born between 1993 and 2003 and treated at the Department of Neonatology at University Hospital Charité, Berlin. In addition, data from lung function tests (infant whole-body plethysmography, tidal breathing analysis and occlusion tests), carried out at a median age of 32 days were analyzed. With the help of these data, we looked for prognostic indicators for a reduced pulmonary outcome. Results: The majority of patients with CDH had a pathological lung function. Respiratory compliance, resistance, thoracic gas volume, respiratory rate and tidal volume differed significantly from the parameters of controls. Further analysis showed an association between duration and intensity of mechanical ventilation and pulmonary outcome. An early prenatal diagnosis of CDH, a non- left-sided hernia, the use of a patch for operative repair or complications like pleural effusion and pulmonary hypertension significantly increased likelihood of abnormal results from subsequent lung function tests. And where there was an impaired pulmonary function, patients were more likely to be hospitalized longer, especially those children with an obstructive-restrictive pattern. Conclusion: Even after successful surgery, most children with a congenital diaphragmatic hernia have a reduced lung function. With certain risk factors it is more likely for these patients to develop a ventilation disorder. This underlines the necessity of a protective ventilation strategy, in order to reduce additional pulmonary sequelae due to barotrauma and oxygen toxicity. It seems sensible to perform early lung function tests on all children with CDH and to refer them to a specialist paediatric pulmonology unit for continuous follow-up

A large-scale whole genome sequence-based analysis discovered novel genetic variants influencing bone mineral density: Results from the GEFOS and UK10K Consortia

International audienc

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.</p