Background: Chylothorax occurs in ~4% of children undergoing cardiac surgery. Treatment requires transition to a medium chain triglyceride (MCT) based formula. Breast milk (EBM) is discontinued due to the presence of long chain triglycerides. Objective: To determine the effectiveness of a modified fat breast milk for the treatment of chylothorax. Methods: Infants with chylothorax were eligible. Treatment infants (n=8) received EBM that had been modified by removing the fat layer (centrifugation) from EBM and adding MCT and nutrients to provide 67 kcal/ml and 11 g/100 ml protein. Control infants (n=8) received MCT formula. Results: Volume of chest tube drainage was not different (p<0.40). Treatment infants experienced declines in mean weight (p<0.006), length (p<0.013) and head circumference (p<0.008) z-scores. Conclusion: Modified fat breast milk allowed for successful resolution of chylothorax. Strategies to address poor growth, however, need to be tested before clinical adoption of this novel treatment.

Background: Chylothorax occurs in ~4% of children undergoing cardiac surgery. Treatment requires transition to a medium chain triglyceride (MCT) based formula. Breast milk (EBM) is discontinued due to the presence of long chain triglycerides. Objective: To determine the effectiveness of a modified fat breast milk for the treatment of chylothorax. Methods: Infants with chylothorax were eligible. Treatment infants (n=8) received EBM that had been modified by removing the fat layer (centrifugation) from EBM and adding MCT and nutrients to provide 67 kcal/ml and 11 g/100 ml protein. Control infants (n=8) received MCT formula. Results: Volume of chest tube drainage was not different (p<0.40). Treatment infants experienced declines in mean weight (p<0.006), length (p<0.013) and head circumference (p<0.008) z-scores. Conclusion: Modified fat breast milk allowed for successful resolution of chylothorax. Strategies to address poor growth, however, need to be tested before clinical adoption of this novel treatment.

Angioimmunoblastic T-cell lymphoma (AITL) is a rare type of lymphoid malignancy with most affected patients presenting in their late 60’s with nonspecific symptoms, laboratory signs and advanced stage disease. 78 year old female with history of hypertension presented to the hospital with complaints of dyspnea, dry cough and fatigue of one week duration. She denied having fever, chills, night sweats or recent weight loss. Labs on admission were significant for leukopenia with lymphocytopenia, thrombocytopenia, hyponatremia and hyperglobulinemia. Computer tomography chest and abdomen showed bilateral multifocal lung infiltrates, large left side pleural effusion, diffuse lymphadenopathy and splenomegaly. She was started on empiric antibiotics for community acquired pneumonia. Sputum culture did not identify any offending organism and although thoracentesis was consistent with exudative fluid, microbiology and pathologic studies also did not offer a diagnosis. Fine needle aspiration of a suspicious lymph node was also negative. She was discharged home to complete treatment for pneumonia but over the next two months, she presented on three different occasions with the same respiratory symptoms. Serial thoracentesis thereafter showed chylous fluid that was fast re-accumulating. A repeat flow cytometry of the pleural fluid was concerning for a lymphoproliferative process and subsequent excisional biopsy with molecular studies performed on rearrangement of T-cell receptors resulted in eventual diagnosis of Angioimmunoblastic T-cell lymphoma stage IV due to associated lung involvement. She declined aggressive management and opted for palliative care. Lymphoma presenting with chylothorax is not common due to early diagnosis of most lymphoma but it can be the initial presentation of AITL because most patients present with nonspecific symptoms and lab findings that make diagnosis difficult and delayed. In our patient, eventual diagnosis was three months from initial presentation. This is not ideal because most patients who succumb to the disease tend to do so from progressive worsening nutritional status and immunosuppression that ensues as the disease advances. The recurrent chylothorax seen in our patient is likely a result of tumor burden that obstructed chyle drainage through the thoracic duct and may have resolved with adequate treatment of the disease. Multiple laboratory abnormalities and B-type symptoms in a patient with unclear primary process should prompt workup for a possible neoplastic disease, particularly lymphoma. Clinicians who suspect a lymphoproliferative process in patients with diffuse lymphadenopathy and pulmonary symptoms of unclear etiology should consider getting an excisional tissue biopsy for further diagnostic studies. PCR based studies that assess for cell locality is also helpful in particularly difficult cases.

No description available.

Lymphatic valves (LVs) are cusped luminal structures that permit the movement of lymph in only one direction and are therefore critical for proper lymphatic vessel function. Congenital valve aplasia or agenesis can, in some cases, be a direct cause of lymphatic disease. Knowledge about the molecular mechanisms operating during the development and maintenance of LVs may thus aid in the establishment of novel therapeutic approaches to treat lymphatic disorders. In this study, we examined the role of Connexin43 (Cx43), a gap junction protein expressed in lymphatic endothelial cells (LECs), during valve development. Mouse embryos with a null mutation in Cx43 (Gja1) were previously shown to completely lack mesenteric LVs at embryonic day 18. However, interpreting the phenotype of Cx43(-/-) mice was complicated by the fact that global deletion of Cx43 causes perinatal death due to heart defects during embryogenesis. We have now generated a mouse model (Cx43(∆LEC)) with a lymphatic-specific ablation of Cx43 and show that the absence of Cx43 in LECs causes a delay (rather than a complete block) in LV initiation, an increase in immature valves with incomplete leaflet elongation, a reduction in the total number of valves, and altered lymphatic capillary patterning. The physiological consequences of these lymphatic changes were leaky valves, insufficient lymph transport and reflux, and a high incidence of lethal chylothorax. These results demonstrate that the expression of Cx43 is specifically required in LECs for normal development of LVs.

Das Krankheitsbild des Chylothorax stellt bei Neugeborenen und Säuglingen eine relevante Komplikation nach einer kinderherzchirurgischen Operation dar. Zusätzlich zu den respiratorischen Einschränkungen durch die Ansammlung von Chylus im Pleuraspalt kommt es zu negativen Auswirkungen auf die Nährstoffversorgung, die Hämostase sowie den Immunstatus der Patienten. Klassischerweise wird der postoperative Chylothorax mit einer diätetischen Restriktion von langkettigen Fettsäuren behandelt, worunter es zu einer Abnahme der Chylusproduktion und somit zu einer Ausheilung kommt. Für die Neugeborenen und Säuglinge bedeutet dies ein Verzicht auf die Ernährung mit Muttermilch. Insbesondere Patienten mit angeborenen Herzfehlern profitieren jedoch von den Vorteilen der Muttermilchernährung, weshalb in einzelnen Fallstudien der Einsatz von fettarmer Muttermilch (Low Fat Breast Milk, LFBM) als alternative Behandlungsmethode des Chylothorax erprobt wurde. Diese Arbeit wertet im Rahmen der ChyloBEST-Studie der Klinik für Kinderkardiologie des Herzzentrums Leipzig gewonnen Daten aus. Die kontrollierte Interventionsstudie untersucht die Wirksamkeit der Chylothoraxtherapie mit LFBM im Vergleich zur Therapie mit der fettfreien Formulanahrung Basic-F® bezüglich des kurzfristigen Krankheitsverlaufs und der körperlichen Entwicklung der Patienten. In die prospektive Interventionsgruppe wurden 13 Patienten mit Chylothorax nach kinderherzchirurgischer Operation eingeschlossen und mit einer retrospektiven Kontrollgruppe von 10 Patienten verglichen. Die LFBM wurde vor Ort mittels gekühlter Zentrifugation hergestellt und vor dem Füttern mit MCT-Öl sowie Muttermilchfortifier angereichert. Laborchemische Untersuchungen von Stichproben der LFBM mit einem Muttermilchanalysator zeigten eine deutliche Abnahme des Fettgehalts im Vergleich zu nativer Muttermilch. Als primäre Endpunkte wurden die Drainagemenge und die Drainagedauer untersucht, da diese beiden Parameter direkt die Chylusproduktion widerspiegeln. In den Punkten Drainagemenge und Drainagedauer zeigt die Behandlung mit LFBM gleichwertige Ergebnisse wie die Standardtherapie mit Basic F. Es bestätigen sich hier die bisher veröffentlichten Ergebnisse anderer Arbeitsgruppen zum Einsatz von LFBM bei postoperativem Chylothorax. Des Weiteren zeigt sich kein signifikanter Unterschied zwischen den Studiengruppen bezüglich der Dauer des postoperativen Intensivaufenthalts und des gesamten postoperativen stationären Klinikaufenthalts. Die körperliche Entwicklung der Patienten wurde anhand des Körpergewichts, der Körperlänge und der Kopfumfangs jeweils zum Zeitpunkt der Operation, zur Entlassung und zu einem Follow-Up-Termin drei Monate nach der Diagnose Chylothorax beurteilt. Durch den Verzicht auf langkettige Fettsäuren in der Nahrung besteht das Risiko einer Nährstoffmangelversorgung, weshalb das Gedeihen der Patienten einen ausschlaggebenden Faktor in der Therapie des Chylothorax darstellt. In beiden Studiengruppen zeigt sich im Verlauf ein verlangsamtes Wachstum im Vergleich zur allgemeinen Population, jedoch lässt sich kein Unterschied zwischen der Behandlung mit LFBM und Basic-F feststellen. In Zusammenschau mit den bisherigen Ergebnissen zur Ernährung mit LFBM zur Behandlung des postoperativen Chylothorax in der Literatur zeigt die ChyloBEST-Studie, dass der Einsatz von LFBM eine wirksame und sichere Alternative zu der Therapie mit fettfreier Formulanahrung darstellt. Weder im kurzfristigen Krankheitsverlauf noch im Wachstum zeigen sich signifikante Unterschiede zwischen den beiden Therapien. Des Weiteren ist die Herstellung und der Einsatz von LFBM kostengünstig und unkompliziert möglich. Die Therapie mit LFBM ermöglicht Neugeborenen und Säuglingen mit postoperativen Chylothorax von den Vorteilen der Muttermilchernährung zu profitieren ohne Nachteile im Krankheitsverlauf oder im Wachstum erwarte.:Einleitung Grundlagen 2.1 Definition des Chylothorax 2.2 Anatomie und Physiologie 2.3 Epidemiologie des Chylothorax 2.4 Ätiologie und Pathogenese des Chylothorax 2.5 Klinik und Komplikationen des Chylothorax 2.6 Diagnostik und Differentialdiagnosen des Chylothorax 2.7 Therapie des postoperativen Chylothorax 2.7.1 Drainage des Chylus 2.7.2 Diätetische Therapie 2.7.3 Medikamentöse Therapie 2.7.4 Interventionelle Therapie 2.8 Muttermilch in der Therapie des Chylothorax Material & Methoden 3.1 Studiendesign der ChyloBEST-Studie 3.1.1 Studienziele 3.1.2 Einschlusskriterien 3.1.3 Ausschlusskriterien 3.1.4 Datenerhebung 3.2 Gewinnung fettarmer Muttermilch 3.3 Datenauswertung und Statistik Ergebnisse 4.1 Inzidenz 4.2 Patientencharakteristika 4.2.1 Anamnestische Basisdaten 4.2.2 Basisdaten Operation 4.2.3 Basisdaten Diagnose 4.3 Kurzfristiger Krankheitsverlauf 4.3.1 Drainagemenge 4.3.2 Liegedauer der Chylusdrainage 4.4 Ernährung 4.4.1 Nährstoffzusammensetzung der LFBM 4.4.2 Dauer der Studiennahrung 4.4.3 Dauer der postoperativen Nahrungssondierung 4.4.4 Nahrung zum Zeitpunkt des Follow-Up 4.5 Postoperativer Klinikaufenthalt 4.5.1 Dauer des postoperativen Intensivaufenthaltes 4.5.2 Dauer des postoperativen stationären Aufenthaltes 4.6 Wachstum 4.6.1 Körpergewicht 4.6.2 Körperlänge 4.6.3 Kopfumfang 4.7 Unerwünschte Ereignisse Diskussion 5.1 Patientencharakteristika 5.2 Kurzfristiger Krankheitsverlauf 5.2.1 Drainagemenge 5.2.2 Liegedauer der Chylusdrainage 5.3 Ernährung 5.4 Postoperativer Klinikaufenthalt 5.5 Wachstum 5.6 Unerwünschte Ereignisse 5.7 Limitationen der Studie 5.8 Bedeutung der Ergebnisse und Ausblick

OBJETIVO: O objetivo deste estudo foi predizer o prognóstico perinatal em fetos com derrame pleural isolado por meio da medida do volume pulmonar estimado pela ultrassonografia tridimensional. MÉTODO: Estudo retrospectivo, entre julho de 2005 e julho de 2010, com 19 fetos com derrame pleural isolado (ausência de causas infecciosas, imunes, anomalias cromossômicas ou estruturais associadas) acompanhados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Os volumes pulmonares foram obtidos pela ultrassonografia tridimensional (Voluson 730 Expert, GE Medical System, Kretzechnick, Áustria) em dois períodos, no momento do diagnóstico (20 26 semanas) e próximo ao parto (duas semanas antecedentes ao parto ou até 36 semanas), e mensurados pela técnica VOCAL (Virtual Organ Computer Aided Analysis) com rotação de 30º. Os volumes obtidos (observados) foram comparados com valores esperados para idade gestacional, e a razão entre o volume total fetal observado/esperado (VPTo/e) foi avaliada de acordo com a mortalidade perinatal e morbidade neonatal (necessidade de ventilação mecânica por mais que 48 horas). RESULTADOS: Dezenove fetos com derrame pleural isolado foram analisados no período do estudo. Doze (63,2%) crianças sobreviveram. Dos sobreviventes, sete (58,3%) apresentaram morbidade respiratória. O VPTo/e no primeiro exame ultrassonográfico não se associou significativamente com mortalidade (VPTo/e: 0,42±0,19 nos sobreviventes contra 0,30±0,08 nos não sobreviventes, p=0,11). No segundo exame, por outro lado, VPTo/e foi significativamente menor nos casos que faleceram (0,24±0,08) em relação aos sobrevivente (0,58±0,21; p<0,01) e nos que necessitaram de ventilação mecânica prolongada (0,35±0,08) comparados aos que não necessitaram (0,68±0,10; p<0.01). CONCLUSÃO: O volume pulmonar fetal medido pela ultrassonografia tridimensional pode ser utilizado para predizer o prognóstico de fetos com derrame pleural isolado. / OBJECTIVE The aim of the present study was to predict the perinatal outcome in isolated pleural effusion using fetal lung volumes assessed by three-dimensional ultrasonography. METHODS: A retrospective study conducted between July 2005 and July 2010, in which 19 fetuses with isolated pleural effusion (absence of infection, immunological causes, chromosomal anomalies and associated structural anomalies) at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Fetal lung volumes were assessed by three-dimensional ultrasonography (Voluson 730 Expert, GE Medical System, Kretzechnick, Áustria) in two periods: at diagnosis (20-26 weeks) and nears the delivery (2 weeks before delivery or at 36 weeks), by VOCAL technique (Virtual Organ Computer Aided Analysis) with rotation of 30o. The observed volumes were compared to expected values for determine gestational age, and the observed/expected total fetal lung volume ratio (o/e-TFLV) was evaluated according to perinatal death and neonatal morbidity (need for mechanical ventilation longer than 48 hours). RESULTS: A total of 19 fetuses with isolated pleural effusion were evaluated during the study period. Twelve (63.2%) infants survived. Among the survivors, seven (58.3%) had severe respiratory distress at birth. The o/e-TFLV at the first ultrasound examination was not associated statistically with mortality (o/e-TLFV: 0.42±0.19 in survivors x 0.30±0.08 among those that died, p=0.11). On the second ultrasound examination, on the other hand, the o/e-TFLV was significantly reduced in those cases that died (0.24±0.08) whilst in survivors (0.58±0.21; p<0.01) and in those that needed mechanical ventilation (0.35±0.08) when compared to those that did not need it (0.68±0.10; p<0.01). CONCLUSION: Fetal lung volumes measured by three-dimensional ultrasonography may be useful to predict perinatal outcome in fetuses with primary pleural effusion

OBJETIVO: O objetivo deste estudo foi predizer o prognóstico perinatal em fetos com derrame pleural isolado por meio da medida do volume pulmonar estimado pela ultrassonografia tridimensional. MÉTODO: Estudo retrospectivo, entre julho de 2005 e julho de 2010, com 19 fetos com derrame pleural isolado (ausência de causas infecciosas, imunes, anomalias cromossômicas ou estruturais associadas) acompanhados no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Os volumes pulmonares foram obtidos pela ultrassonografia tridimensional (Voluson 730 Expert, GE Medical System, Kretzechnick, Áustria) em dois períodos, no momento do diagnóstico (20 26 semanas) e próximo ao parto (duas semanas antecedentes ao parto ou até 36 semanas), e mensurados pela técnica VOCAL (Virtual Organ Computer Aided Analysis) com rotação de 30º. Os volumes obtidos (observados) foram comparados com valores esperados para idade gestacional, e a razão entre o volume total fetal observado/esperado (VPTo/e) foi avaliada de acordo com a mortalidade perinatal e morbidade neonatal (necessidade de ventilação mecânica por mais que 48 horas). RESULTADOS: Dezenove fetos com derrame pleural isolado foram analisados no período do estudo. Doze (63,2%) crianças sobreviveram. Dos sobreviventes, sete (58,3%) apresentaram morbidade respiratória. O VPTo/e no primeiro exame ultrassonográfico não se associou significativamente com mortalidade (VPTo/e: 0,42±0,19 nos sobreviventes contra 0,30±0,08 nos não sobreviventes, p=0,11). No segundo exame, por outro lado, VPTo/e foi significativamente menor nos casos que faleceram (0,24±0,08) em relação aos sobrevivente (0,58±0,21; p<0,01) e nos que necessitaram de ventilação mecânica prolongada (0,35±0,08) comparados aos que não necessitaram (0,68±0,10; p<0.01). CONCLUSÃO: O volume pulmonar fetal medido pela ultrassonografia tridimensional pode ser utilizado para predizer o prognóstico de fetos com derrame pleural isolado. / OBJECTIVE The aim of the present study was to predict the perinatal outcome in isolated pleural effusion using fetal lung volumes assessed by three-dimensional ultrasonography. METHODS: A retrospective study conducted between July 2005 and July 2010, in which 19 fetuses with isolated pleural effusion (absence of infection, immunological causes, chromosomal anomalies and associated structural anomalies) at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Fetal lung volumes were assessed by three-dimensional ultrasonography (Voluson 730 Expert, GE Medical System, Kretzechnick, Áustria) in two periods: at diagnosis (20-26 weeks) and nears the delivery (2 weeks before delivery or at 36 weeks), by VOCAL technique (Virtual Organ Computer Aided Analysis) with rotation of 30o. The observed volumes were compared to expected values for determine gestational age, and the observed/expected total fetal lung volume ratio (o/e-TFLV) was evaluated according to perinatal death and neonatal morbidity (need for mechanical ventilation longer than 48 hours). RESULTS: A total of 19 fetuses with isolated pleural effusion were evaluated during the study period. Twelve (63.2%) infants survived. Among the survivors, seven (58.3%) had severe respiratory distress at birth. The o/e-TFLV at the first ultrasound examination was not associated statistically with mortality (o/e-TLFV: 0.42±0.19 in survivors x 0.30±0.08 among those that died, p=0.11). On the second ultrasound examination, on the other hand, the o/e-TFLV was significantly reduced in those cases that died (0.24±0.08) whilst in survivors (0.58±0.21; p<0.01) and in those that needed mechanical ventilation (0.35±0.08) when compared to those that did not need it (0.68±0.10; p<0.01). CONCLUSION: Fetal lung volumes measured by three-dimensional ultrasonography may be useful to predict perinatal outcome in fetuses with primary pleural effusion