ABSTRACT
PURPOSE: Middle ear effusion (MEE) is one of the reasons for screening failure and may require prolonged follow-up due to conductive hearing loss. We aimed to examine at 1-year follow-up, the fate of MEE. METHODS: From medical charts, computerized data were collected retrospectively of newborns born in the years 2012-2013 in Rambam Health Care Campus, Haifa city, Israel, who failed the Universal Newborn Hearing Screening (UNHS), and follow-up hearing evaluation data were extracted. RESULTS: Of 9527 newborns born in 2012-2013 in our institution, 144 [1.5%] failed the UNHS, and 46 were eventually diagnosed with conductive hearing loss caused by MEE. Spontaneous MEE clearance was recorded in 12 [26%], while 26 [57%] patients had persistent effusion that required further follow-up (10 [22%] required insertion of ventilation tubes and 16 [35%] were referred for further follow-up); 8 [17%] were lost to follow-up. CONCLUSION: Congenital MEE causing conductive hearing loss and UNHS failure is persistent and resolves at lower rates than non-congenital MEE.
Subject(s)
Otitis Media with Effusion , Humans , Infant, Newborn , Infant , Otitis Media with Effusion/complications , Otitis Media with Effusion/diagnosis , Otitis Media with Effusion/surgery , Hearing Loss, Conductive/diagnosis , Hearing Loss, Conductive/etiology , Retrospective Studies , Hearing Tests , Neonatal Screening/adverse effects , HearingABSTRACT
Background: Radioactive iodine (RAI) is the mainstay of treatment for differentiated thyroid carcinoma (DTC). Nevertheless, the mechanism of RAI resistance that occurs in many patients with DTC remains unknown. We aimed to elucidate the role of post-translational regulation of radioiodine uptake. Methods: We analyzed the expression pattern of the ribosomal glycosylphosphatidylinositol transamidase (GPIT) complex in freshly excised tumors from 10 patients with DTC. We used functional RAI uptake assays to assess the role of GPIT in iodine uptake both in vivo and in vitro. The effects of MEK inhibition on the GPIT subunit PIGU and the sodium iodide symporter (NIS) were assessed in three DTC cell lines and in four human DTC biopsies. We used a multivariable logistic regression model to study the role of PIGU in the response to RAI treatment in advanced DTC. All statistical tests were two-sided. Results: Expression profiling of different GPIT complex subunits revealed statistically significantly lower expression of PIGU in papillary carcinomas than in matched normal thyroid tissue (P < .001). Expression of PIGU in the K1 human papillary carcinoma cell line resulted in a robust increase in NIS glycosylation and trafficking to the cell membrane, accompanied by a robust increase in I125 uptake both in vitro (465 200 ± 56 343 vs 1236 ± 156 counts per million, P < .001) and in vivo (128 945 ± 28 556 vs 7963 ± 192 counts per million, P < .001, n = 5 mice per group). Treatment with the MEK inhibitors U0126 and PD302 rescued PIGU expression. Finally, the PIGU expression levels in tumors of 18 patients with recurrent DTC were associated with a biochemical response to RAI treatment (hazard ratio = 8.06, 95% confidence interval = 3.72 to 12.3, P = .001). Conclusions: We showed that downregulation of PIGU in DTC determines NIS function and RAI avidity. This represents a novel mechanism for RAI resistance.
Subject(s)
Acyltransferases/metabolism , Carcinoma, Papillary/pathology , Iodine Radioisotopes/therapeutic use , Protein Processing, Post-Translational , Radiation Tolerance , Symporters/metabolism , Thyroid Neoplasms/pathology , Acyltransferases/genetics , Adult , Aged , Carcinoma, Papillary/metabolism , Carcinoma, Papillary/radiotherapy , Case-Control Studies , Female , Glycosylation , Humans , Male , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/radiotherapy , Symporters/genetics , Thyroid Gland/metabolism , Thyroid Gland/pathology , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/radiotherapy , Young AdultABSTRACT
BACKGROUND: Myocardial stunning is responsible for partially reversible left ventricular (LV) systolic dysfunction after successful primary percutaneous coronary intervention (PPCI) in patients with acute ST-elevation myocardial infarction (STEMI). AIM: To test the hypothesis that early coronary blood flow (CBF) to LV systolic function ratios, as an equivalent to LV stunning index (SI), predict recovery of LV systolic function after PPCI in patients with acute STEMI. METHODS: Twenty-four patients with acute anterior STEMI who had successful PPCI were evaluated and compared to 96 control subjects. Transthoracic echocardiography with measurement of LV ejection fraction (EF), LV, and left anterior descending (LAD) coronary artery area wall-motion score index (WMSI) as well as Doppler sampling of LAD blood velocities, early after PPCI and 5 days later, were performed. SI was evaluated as the early ratio of CBF parameters in the LAD to LV systolic function parameters. RESULTS: Early SI-LVEF well predicted late LVEF (r=.51, P<.01) and the change in LVEF (r=.48, P<.017). Early SI-LVMSI predicted well late LVEF (r=.56, P<.006) and the change in LVEF (r=.46, P<.028). Early SI-LADWMSI predicted late LVEF (r=.44, P<.028). Other SI indices measured as other LAD-CBF to LV systolic function parameters were not predictive of late LV systolic function. CONCLUSIONS: LV stunning indices measured as early LAD flow to LVEF, LVWMSI, and LADWMSI ratios well predicted late LVEF and the change in LVEF. Thus, greater early coronary artery flow to LV systolic function parameter ratios predict a better improvement in late LV systolic function after PPCI.
