Elective Tympanostomy Tube Removal at 2.5 Years: Results of a Protocol for Retained Tubes.

OBJECTIVES: In 2001, we instituted a protocol for the removal of retained tympanostomy tubes, delaying elective removal until 2.5 years after placement. It was hoped that this would decrease the number of surgeries without increasing the rate of permanent tympanic perforations compared to removal at 2 years. METHODS: Protocol: Fluoroplastic Armstrong beveled grommet tympanostomy tubes were placed by a single surgeon supervising the residents. The children were seen at 6-month intervals after placement. Children with a retained tympanostomy tube(s) at 2 years were seen again at 2.5 years, and the retained tubes were removed under general anesthesia with patch application. All were evaluated 4 weeks after surgery by otoscopy, otomicroscopy, behavioral audiometry, and tympanometry. STUDY: A computerized collection of patient letters and operative reports was queried to identify children treated according to the protocol between 2001 and 2022. Those with examinations at 2 years ± 1 month and 2.5 years ± 1 month and complete follow-up were included. RESULTS: Of the 3552 children with tympanostomy tubes, 497 (14%) underwent tube removal. One-hundred and forty seven children fit the strict inclusion criteria. Among those with retained tubes at 2 years, 67/147 (46%) had lost any remaining tube or tubes at 2.5 years and did not need surgery, 80/147 (54%) required unilateral or bilateral tube removal, 9/147 (6%) had a persistent perforation at 1-year follow-up, and 4/147 children (3%) required tympanic re-intubation after either spontaneous extrusion or removal and patching at 2.5 years. CONCLUSIONS: Delaying tympanostomy tube removal until 2.5 years can cut the need for surgery in half with, an acceptable (6%) incidence of persistent perforations. LEVEL OF EVIDENCE: Four case series-historical control Laryngoscope, 134:439-442, 2024.

Breast cancer cells that preferentially metastasize to lung or bone are more glycolytic, synthesize serine at greater rates, and consume less ATP and NADPH than parent MDA-MB-231 cells.

Gene expression signatures associated with breast cancer metastases suggest that metabolic re-wiring is important for metastatic growth in lungs, bones, and other organs. However, since pathway fluxes depend on additional factors such as ATP demand, allosteric effects, and post-translational modification, flux analysis is necessary to conclusively establish phenotypes. In this study, the metabolic phenotypes of breast cancer cell lines with low (T47D) or high (MDA-MB-231) metastatic potential, as well as lung (LM)- and bone (BoM)-homing lines derived from MDA-MB-231 cells, were assessed by 13C metabolite labeling from [1,2-13C] glucose or [5-13C] glutamine and the rates of nutrient and oxygen consumption and lactate production. MDA-MB-231 and T47D cells produced 55 and 63%, respectively, of ATP from oxidative phosphorylation, whereas LM and BoM cells were more glycolytic, deriving only 20-25% of their ATP from mitochondria. ATP demand by BoM and LM cells was approximately half the rate of the parent cells. Of the anabolic fluxes assessed, nucleotide synthesis was the major ATP consumer for all cell lines. Glycolytic NADH production by LM cells exceeded the rate at which it could be oxidized by mitochondria, suggesting that the malate-aspartate shuttle was not involved in re-oxidation of these reducing equivalents. Serine synthesis was undetectable in MDA-MB-231 cells, whereas 3-5% of glucose was shunted to serine by LM and BoM lines. Proliferation rates of T47D, BoM, and LM lines tightly correlated with their respiration-normalized NADPH production rates. In contrast, MDA-MB-231 cells produced NADPH and GSH at higher rates, suggesting this line is more oxidatively stressed. Approximately half to two-thirds of NADPH produced by T47D, MDA-MB-231, and BoM cells was from the oxidative PPP, whereas the majority in LM cells was from the folate cycle. All four cell lines used the non-oxidative PPP to produce pentose phosphates, although this was most prominent for LM cells. Taken together, the metabolic phenotypes of LM and BoM lines differed from the parent line and from each other, supporting the metabolic re-wiring hypothesis as a feature of metastasis to lung and bone.