Relapse-related factors of Le Fort I osteotomy in cleft lip and palate patients: A systematic review and meta-analysis.

A systematic review search was based on the PICOS approach, as follows: population: cleft lip and palate patients; intervention: Le Fort I osteotomy; comparator: different surgical protocols; outcome: stability, recurrence or surgical complications; study designs: only case reports were excluded from the review. No restrictions were placed on language or year of publication. Risk of bias was analyzed, heterogeneity was assessed, and subgroup analysis was performed using a level of significance of 1% (p = 0.01). The search identified 248 citations, from which 29 studies were selected and a total of 797 patients enrolled. The level of agreement between the authors was considered excellent (k = 0.810 for study selection and k = 0.941 for study eligibility). Our results reported a mean maxillary advancement of 5.69 mm, a mean vertical downward/upward of 2.85/-2.02 mm and a mean clockwise rotation of 4.15°. Greater surgical relapse rates were reported for vertical downward movement (-1.13 mm, 39.6%), followed by clockwise rotation (-1.41°, 33.9%), sagittal (-0.99 mm, 17.4%) and vertical upward (0.11 mm, 5.4%) movements. No relevance was found regarding the type of cleft, the type of Le Fort I osteotomy, concomitant bone grafting, surgical overcorrection, postoperative rigid or elastic intermaxillary fixation, or retention splint. Study limitations were heterogeneity and the low number of high-quality studies. In spite of reported high relapse rates, Le Fort I osteotomy for maxillary reposition is the first-choice procedure for selected cleft lip and palate patients in whom extensive maxillary movements are not required, because of its safety and its three-dimensional movement versatility in one-step surgery. Otherwise, distraction osteogenesis should be considered as the gold standard treatment.

Evolutionary origins of the estrogen signaling system: insights from amphioxus.

Classically, the estrogen signaling system has two core components: cytochrome P450 aromatase (CYP19), the enzyme complex that catalyzes the rate limiting step in estrogen biosynthesis; and estrogen receptors (ERs), ligand activated transcription factors that interact with the regulatory region of target genes to mediate the biological effects of estrogen. While the importance of estrogens for regulation of reproduction, development and physiology has been well-documented in gnathostome vertebrates, the evolutionary origins of estrogen as a hormone are still unclear. As invertebrates within the phylum Chordata, cephalochordates (e.g., the amphioxus of the genus Branchiostoma) are among the closest invertebrate relatives of the vertebrates and can provide critical insight into the evolution of vertebrate-specific molecules and pathways. To address this question, this paper briefly reviews relevant earlier studies that help to illuminate the history of the aromatase and ER genes, with a particular emphasis on insights from amphioxus and other invertebrates. We then present new analyses of amphioxus aromatase and ER sequence and function, including an in silico model of the amphioxus aromatase protein, and CYP19 gene analysis. CYP19 shares a conserved gene structure with vertebrates (9 coding exons) and moderate sequence conservation (40% amino acid identity with human CYP19). Modeling of the amphioxus aromatase substrate binding site and simulated docking of androstenedione in comparison to the human aromatase shows that the substrate binding site is conserved and predicts that androstenedione could be a substrate for amphioxus CYP19. The amphioxus ER is structurally similar to vertebrate ERs, but differs in sequence and key residues of the ligand binding domain. Consistent with results from other laboratories, amphioxus ER did not bind radiolabeled estradiol, nor did it modulate gene expression on an estrogen-responsive element (ERE) in the presence of estradiol, 4-hydroxytamoxifen, diethylstilbestrol, bisphenol A or genistein. Interestingly, it has been shown that a related gene, the amphioxus "steroid receptor" (SR), can be activated by estrogens and that amphioxus ER can repress this activation. CYP19, ER and SR are all primarily expressed in gonadal tissue, suggesting an ancient paracrine/autocrine signaling role, but it is not yet known how their expression is regulated and, if estrogen is actually synthesized in amphioxus, whether it has a role in mediating any biological effects. Functional studies are clearly needed to link emerging bioinformatics and in vitro molecular biology results with organismal physiology to develop an understanding of the evolution of estrogen signaling. This article is part of a Special Issue entitled 'Marine organisms'.