The unilateral cleft lip repair.

OBJECTIVE: To determine if there is a benefit of 2-stage cleft lip repair in regard to improving facial symmetry and facilitating definitive lip, nose, and palate repair. STUDY DESIGN: Retrospective chart review of patients born with complete, unilateral cleft lip deformity that underwent a two-stage repair described as a stage 1 straight line repair and a stage 2 modified Millard repair, for which a complete set of records, and peri-operative and post-operative photos were available. All cases were performed by a single surgeon. SETTING: Tertiary care center craniofacial team. METHODS: Measurements were taken from intraoperative, perioperative, and postoperative images of patients before and after each stage. Ratios were then created comparing the affected size to the unaffected side, and these were averaged between observers. RESULTS: A 19% increase in the width of area of the presumptive C flap was obtained between the unrepaired and the post-stage I images. The nostril width of the cleft side was 1.2× the width of the unaffected side, demonstrating a 140% decrease in nostril width at the completion of stage II. The cleft side nostril width was maintained slightly larger than the noncleft side as desired. Symmetry of the upper lip length was achieved, as the length of the cleft side lateral lip after stage II was 92% of the unaffected side. CONCLUSION: We believe this study provides evidence for our observations that a two-stage repair can be performed with functionally and aesthetically pleasing outcomes as an alternative to presurgical nasoalveolar molding.

Septal fractures predict poor outcomes after closed nasal reduction: Retrospective review and survey.

OBJECTIVES/HYPOTHESIS: To determine outcomes of patients with displaced nasal bone fractures after closed nasal reduction (CNR). STUDY DESIGN: Retrospective patient review. METHODS: Review of all patients presenting to the emergency department of a tertiary-care, level 1 trauma hospital with a nasal bone fracture over a 2-year period, followed by telephone survey after CNR. RESULTS: Six hundred seven patients presented to the emergency department in 2015 and 2016 with a diagnosis of nasal bone fracture. Of these, 134 patients met inclusion criteria and underwent CNR without septal reduction. Those with sports-related injuries and those with a septal fracture identified on computed tomography imaging were significantly more likely to undergo CNR. Ninety-one patients completed the post-CNR telephone survey. Over 90% of patients were satisfied with the procedure. However, patients with septal fractures reported worse outcomes, as 53.6% versus 24.1% (P = .0025) disagreed that CNR improved nasal breathing. Of all patients, 11 (2%) eventually underwent septorhinoplasty, with the presence of septal fracture on imaging a significant risk factor. CONCLUSIONS: Nasal bone fractures are a common injury, often managed initially with CNR. Patients with septal fractures should be counseled on the high risk of posttraumatic nasal deformity and obstruction despite CNR. In addition, addressing a septal fracture found on imaging may be warranted with either closed septal reduction or early aggressive management given the poorer outcomes seen in the present study. Although these patients are more likely to have definitive treatment, many forego later intervention despite persistent symptoms, emphasizing the need for early intervention or close follow-up. LEVEL OF EVIDENCE: 3 Laryngoscope, 129:1784-1790, 2019.

d-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models.

BACKGROUND: Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested d-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. METHODS: Auditory brainstem responses (ABRs) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of d-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic Escherichia coli murine survival and intraperitoneal lavage bacterial counts. RESULTS: d-Methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20kHz in the 420mg/kg/day group. In vitro studies did not detect d-methionine-induced antimicrobial interference. In vivo studies did not detect d-methionine-induced interference in normal or neutropenic mice. CONCLUSIONS: d-Methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest d-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients.

Organotins are potent activators of PPARγ and adipocyte differentiation in bone marrow multipotent mesenchymal stromal cells.

Adipocyte differentiation in bone marrow is potentially deleterious to both bone integrity and lymphopoiesis. Here, we examine the hypothesis that organotins, common environmental contaminants that are dual ligands for peroxisome proliferator-activated receptor (PPAR) γ and its heterodimerization partner retinoid X receptor (RXR), are potent activators of bone marrow adipogenesis. A C57Bl/6-derived bone marrow multipotent mesenchymal stromal cell (MSC) line, BMS2, was treated with rosiglitazone, a PPARγ agonist, bexarotene, an RXR agonist, or a series of organotins. Rosiglitazone and bexarotene potently activated adipocyte differentiation; however, bexarotene had a maximal efficacy of only 20% of that induced by rosiglitazone. Organotins (tributyltin [TBT], triphenyltin, and dibutyltin) also stimulated adipocyte differentiation (EC50 of 10-20 nM) but with submaximal, structure-dependent efficacy. In coexposures, both bexarotene and TBT enhanced rosiglitazone-induced adipogenesis. To investigate the contribution of PPARγ to TBT-induced adipogenesis, we examined expression of PPARγ2, as well as its transcriptional target FABP4. TBT-induced PPARγ2 and FABP4 protein expression with an efficacy intermediate between rosiglitazone and bexarotene, similar to lipid accumulation. A PPARγ antagonist and PPARγ-specific small hairpin RNA suppressed TBT-induced differentiation, although to a lesser extent than rosiglitazone-induced differentiation, suggesting that TBT may engage alternate pathways. TBT and bexarotene, but not rosiglitazone, also induced the expression of TGM2 (an RXR target) and ABCA1 (a liver X receptor target). The results show that an environmental contaminant, acting with the same potency as a therapeutic drug, induces PPARγ-dependent adipocyte differentiation in bone marrow MSCs. Activation of multiple nuclear receptor pathways by organotins may have significant implications for bone physiology.