Sirt5 is dispensable for BrafV600E‐mediated cutaneous melanoma development and growth in vivo

Sirt5 is known to functionally regulate mitochondrial proteins by altering posttranslational modifications, including lysine desuccinylation. While roles for Sirt5 as either a tumor promoter or suppressor, or in chemoresistance, have been implicated in other cancers, the function of Sirt5 in cutaneous melanoma has not been well examined. Therefore, to determine whether Sirt5 is necessary for Braf^V600E‐mediated melanoma formation and/or disease progression, we crossed a genetically engineered murine melanoma model (Tyr^CreERT2/+; Braf^{LSL‐V600E/+}; Pten^flox/flox) to Sirt5^?/? knockout animals. In addition, we tested for synergism with a selective BRAF (V600E) inhibitor in Sirt5^?/? mouse melanoma cells. Taken together, this report demonstrates that, in these models, Sirt5 is dispensable for Braf^V600E‐mediated cutaneous melanoma formation and growth in vivo, and does not improve sensitivity to a selective BRAF inhibitor.     

Congenital high airway obstruction syndrome (CHAOS): Natural history,prenatal management strategies,and outcomes at a single comprehensive fetal center

PurposeCongenital high airway obstruction syndrome (CHAOS) is a devastating fetal condition of complete airway discontinuity resulting in significant hydrops and extreme lung hyperplasia. It is universally fatal with survival reported only in the rare spontaneous fistulization or EXIT intervention (Ex Utero Intrapartum Treatment). Even in these cases, mortality remains high, and current investigations are targeting prenatal interventions. This report describes our experience with management and fetal interventions for CHAOS, including laser laryngotomy.MethodsWe retrospectively reviewed all patients diagnosed with CHAOS at a single academic institution between 2006 and 2017.ResultsFifteen patients were identified. Eight had obstruction at the trachea and seven at the larynx. In the laryngeal obstructions, three expired shortly after birth, and one survived after spontaneous fistulization and subsequent EXIT to tracheostomy. The remaining three underwent in-utero treatment with laser laryngotomy. One had preterm premature rupture of membranes (PPROM), delivered 3 days post-operatively, and died. Two underwent EXIT to tracheostomy with one surviving to discharge and is currently 2 years old.ConclusionOur study demonstrates the outcomes of a large series of patients diagnosed with CHAOS. While mortality remains high, options for fetal intervention are being explored to allow alterations in the prenatal natural history and improve postnatal outcomes.Type of StudyRetrospective Treatment Study.Level of EvidenceLevel IV.     

伴随结节性硬化的浸润性视网膜星形细胞瘤4例

众所周知，视网膜星形细胞瘤常伴有结节性硬化的表现。视网膜星形细胞瘤一般是发生在视网膜神经纤维层的无蒂轻度隆起性病变。临床上可以是单侧发生，也可以是双侧发生。可以单个病灶，也可以多个病灶。可以是透明的，也可以是不透明的。可以有钙化，也可以没有钙化。视网膜星形细胞瘤相对固定的伴有眼内结节性硬化，很少表现为浸润性增长。在很少的情况下视网膜星形细胞瘤可以表现出浸润性增长，造成局部严重并发症。