Impact of outcomes data on the management of postoperative hypocalcemia in head and neck endocrine surgery patients.

Postoperative hypocalcemia is a well-described outcome following thyroid and parathyroid surgery with symptoms ranging from clinically insignificant laboratory findings to tetany and seizures. The aims of this study were 1. To identify the characteristics and management patterns of postoperative hypocalcemia in head and neck endocrine surgery patients and 2. To compare outcomes between patients treated with empiric calcium and patients treated using a biochemically driven calcium replacement algorithm. Clinical electronic medical record (EMR) data was collected from patients who had undergone total thyroidectomy, completion thyroidectomy, and/or parathyroidectomy at Wake Forest Baptist Medical Center (WFBMC), a tertiary referral and academic institution. Between July 1, 2016, and June 30, 2017, 298 adult patients underwent surgery by a WFBMC Head & Neck (H&N) endocrine surgeon. Objective calcium and parathyroid hormone levels, postoperative supplementation with calcium and Vitamin D, 30-day physician access line (PAL) phone call utilization, emergency department (ED) encounters, and readmission rates were queried. The overall rate of hypocalcemia was 17.4%. No statistically significant difference in PAL utilization, ED visits, or readmissions was found between the empiric supplementation group and those whose supplementation was biochemically directed (PAL 5.0% vs. 5.0% [p = 0.983], ED visit 3.3% vs. 2.5% [p = 0.744], Readmission 1.7% vs. 0% [p = 0.276]). The overall postoperative rates of hypocalcemia and hypoparathyroidism following H&N endocrine surgery were consistent with the reported literature. Neither method of calcium supplementation was superior in reducing PAL utilization, ED encounters, or readmission.

Surgical management of Eagle syndrome: A 17-year experience with open and transoral robotic styloidectomy.

Eagle Syndrome (ES) is a rare disorder that can present with symptoms ranging from globus sensation to otalgia that is attributed to an elongated styloid process and/or calcified stylohyoid ligament. No standardized treatment algorithm exists, and although various surgical approaches have been described, data on the use of transoral robotic surgery (TORS) in this population is limited. To investigate the utility of TORS in the treatment of ES, a retrospective review in 19 ES patients was carried out at a single academic, tertiary medical center between 2000 and 2017. Nineteen patients underwent twenty-one styloid resections: 6 performed via TORS and 15 via transcervical approach. Across all patients, 90% reported some degree of lasting improvement in symptoms while 55% reported significant improvement. When TORS was compared to transcervical resection, there was no difference in the subjective rate of "meaningful" (83 vs. 57%) versus rate of "non-meaningful" symptom improvement (17 vs. 43%) (p = 0.35). There was a trend towards less estimated blood loss (EBL), operative time, and post-operative length of stay (LOS) with TORS versus transcervical cases (9.2 mL vs. 30.0 mL, 98 vs. 156 min, and 0.7 vs. 1.2 days); however, these did not reach statistical significance (p = .11, 0.13, and 0.42, respectively). Three patients experienced complications associated with an open approach, as compared to none with TORS. In select patients, TORS styloidectomy is a reasonable surgical alternative to traditional transoral and transcervical techniques as it provides similar symptom improvement, and reduced length of stay, blood loss, and operative time.

Endogenous opioid inhibition of proliferation of T and B cell subpopulations in response to immunization for experimental autoimmune encephalomyelitis.

BACKGROUND: Experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, is induced by immunization of mice with myelin oligodendrocytic glycoprotein (MOG35-55) injections, and after 9 days, mice develop behavioral signs of chronic progressive EAE. Proliferation of T and B cells located in peripheral lymph tissues such as spleen and inguinal lymph nodes of C57BL/6J mice are stimulated. The opioid growth factor-opioid growth factor receptor (OGF-OGFr) axis has been shown to effectively limit progression of chronic EAE when mice are treated at the time of induction or at time of established disease. In addition to repressed behavioral profiles, spinal cord neuropathology is diminished in mice treated with OGF or low dosages of naltrexone (LDN). However, there is little or no information on peripheral lymphocyte dynamics following immunization of mice with MOG antigen and treatment with OGF or LDN. METHODS: Six-week old female mice were immunized with MOG35-55 and were injected intraperitoneally with OGF or a low dosage of naltrexone (LDN) beginning at the time of immunization; saline-injected immunized mice served as controls. Normal mice received saline for all injections. Periodically over a 2 week period, spleens and inguinal lymph nodes were removed, total lymphocytes counted, and subpopulations of CD4+ and CD8+ specific T-cells, as well as B lymphocytes, were determined by flow cytometry. On day 15 of treatment, lumbar spinal cord tissue was removed; CNS lymphocytes isolated, and assayed for Th1, Th2, and Th17 markers by flow cytometry. RESULTS: Exogenous OGF or endogenous OGF following LDN suppressed T and B lymphocyte proliferation in the spleen and inguinal lymph nodes of MOG-immunized mice. Suppression of peripheral immune cell CD4+ and CD8+ T cell proliferation at 5 and 12 days correlated with reductions in clinical behavior. EAE mice treated with OGF for 15 days displayed elevated Th1 and Th17 cells; no subpopulations of Th2-specific T cells were noted. CONCLUSIONS: OGF or LDN repress proliferation of CD4+ and CD8+T cells and B220+ B lymphocytes in the spleen and lymph nodes of immunized mice within a week of immunization. These data provide novel mechanistic pathways underlying the efficacy of OGF and LDN therapy for MS.

Profibrotic role of miR-154 in pulmonary fibrosis.

In this study, we explored the regulation and the role of up-regulated microRNAs in idiopathic pulmonary fibrosis (IPF), a progressive interstitial lung disease of unknown origin. We analyzed the expression of microRNAs in IPF lungs and identified 43 significantly up-regulated microRNAs. Twenty-four of the 43 increased microRNAs were localized to the chromosome 14q32 microRNA cluster. We validated the increased expression of miR-154, miR-134, miR-299-5p, miR-410, miR-382, miR-409-3p, miR-487b, miR-31, and miR-127 by quantitative RT-PCR and determined that they were similarly expressed in embryonic lungs. We did not find evidence for differential methylation in this region, but analysis of transcription factor binding sites identified multiple SMAD3-binding elements in the 14q32 microRNA cluster. TGF-ß1 stimulation of normal human lung fibroblasts (NHLF) caused up-regulation of microRNAs on chr14q32 that were also increased in IPF lungs. Chromatin immunoprecipitation confirmed binding of SMAD3 to the putative promoter of miR-154. Mir-154 was increased in IPF fibroblasts, and transfection of NHLF with miR-154 caused significant increases in cell proliferation and migration. The increase in proliferation induced by TGF-ß was not observed when NHLF or IPF fibroblasts were transfected with a mir-154 inhibitor. Transfection with miR-154 caused activation of the WNT pathway in NHLF. ICG-001 and XAV939, inhibitors of the WNT/ß-catenin pathway, reduced the proliferative effect of miR-154. The potential role of miR-154, one of multiple chr14q32 microRNA cluster members up-regulated in IPF and a regulator of fibroblast migration and proliferation, should be further explored in IPF.

Association of Thyroid Nodule Size and Bethesda Class With Rate of Malignant Disease.

IMPORTANCE: The ability to accurately stratify patients with thyroid nodules (TNs) preoperatively is imperative because most TNs are benign. The reliability of fine-needle aspiration biopsy (FNAB) in large TNs has been questioned in recent literature. OBJECTIVE: To determine whether TN size affects the reliability of FNAB results, and to determine the rates of malignant disease of each Bethesda class at Penn State Medical Center. DESIGN, SETTING, AND PARTICIPANTS: Retrospective electronic medical record review of patients undergoing FNAB followed by thyroidectomy from March 2010 through December 2013 at an academic, tertiary referral center. A total of 297 patients with 326 TNs were identified as part of a consecutive series. MAIN OUTCOMES AND MEASURES: The primary outcome was to determine the rate of malignant disease of TNs smaller than 3.0 cm or 3.0 cm or larger and of each Bethesda class. Statistical analysis included χ(2) tests. The secondary outcome was to develop logistic regression models to estimate the probability of malignant disease on final pathologic diagnosis as predicted by TN size as well as TN size in conjunction with Bethesda class. RESULTS: Of the 297 patients, 233 were female (78.4%). The mean (SD) age was 51.0 (15.4) years. Of the 326 TNs, 143 were malignant on surgical histopathologic analysis (43.7%). The mean TN size was 2.0 (1.4) cm. Rates of malignant disease for Bethesda classes 1 to 6 were 0% (95% CI, 0%-26.0%), 6.0% (95% CI, 1.7%-14.6%), 30.2% (95% CI, 18.3%-44.3%), 23.5% (95% CI, 14.8%-34.2%), 72.4% (95% CI, 52.8%-87.3%), and 98.8% (95% CI, 93.5%-99.9%), respectively. Overall sensitivity and specificity (excluding class 1 TNs) were 97.2% and 36.8%, respectively. The false-negative rate of benign cytologic results was 6.0% (95% CI, 1.7%-14.6%); only 1 false-negative result occurred in TNs 3.0 cm or greater. Of the TNs smaller than 3.0 cm, 48.4% were malignant compared with 33.3% of TNs 3.0 cm or greater (P = .049). Both Bethesda class and TN size were significant variables (P < .05) within our logistic regression models indicating that higher Bethesda class and TN size smaller than about 2.0 cm were associated with increased probabilities of malignant disease. CONCLUSIONS AND RELEVANCE: Our results suggest that smaller TNs (smaller than about 2.0 cm) are associated with increased probabilities of malignant disease irrespective of Bethesda class. Routine diagnostic thyroid lobectomy solely owing to TN size of 3.0 cm or greater need not be performed.

The isolation and characterization of renal cancer initiating cells from human Wilms' tumour xenografts unveils new therapeutic targets.

There are considerable differences in tumour biology between adult and paediatric cancers. The existence of cancer initiating cells/cancer stem cells (CIC/CSC) in paediatric solid tumours is currently unclear. Here, we show the successful propagation of primary human Wilms' tumour (WT), a common paediatric renal malignancy, in immunodeficient mice, demonstrating the presence of a population of highly proliferative CIC/CSCs capable of serial xenograft initiation. Cell sorting and limiting dilution transplantation analysis of xenograft cells identified WT CSCs that harbour a primitive undifferentiated-NCAM1 expressing-"blastema" phenotype, including a capacity to expand and differentiate into the mature renal-like cell types observed in the primary tumour. WT CSCs, which can be further enriched by aldehyde dehydrogenase activity, overexpressed renal stemness and genes linked to poor patient prognosis, showed preferential protein expression of phosphorylated PKB/Akt and strong reduction of the miR-200 family. Complete eradication of WT in multiple xenograft models was achieved with a human NCAM antibody drug conjugate. The existence of CIC/CSCs in WT provides new therapeutic targets.