Overexpression of miRNA 4451 is Associated With a Poor Survival of Patients With Hypopharyngeal Cancer After Surgery With Postoperative Radiotherapy

Hypopharyngeal cancer (HC) is the most common subset of head and neck cancers. These tumors often have an aggressive clinical outcome characterized by local invasion and regional nodal metastasis. Upregulated miRNAs might be useful as biomarkers for prognosis and molecular targets for these tumors. We determined tumor expression of candidate miRNAs using microarray in 8 HC patients and validated in 372 HC patients. We also used paired tumorous and mucosal tissue to verify the miRNA expression. Log-rank test and Cox model were used to evaluate the survival; and Harrell's C-index was used to compare concordance of Cox models. Our results indicated 7 miRNAs aberrantly expressed in HC. Three of these candidate miRNAs (miRNA-4415, miRNA-200a, and miRNA-30b) were selected for further qRT-PCR validation and all of them were frequently found upregulated in HC tumors; with miR-4451 being the most differentially expressed. Moreover, high expression of miR-4451 was positively correlated with advanced tumor stage and increased mortality risk (HR: 1.6, 95% CI: 1.2–2.3; adjusted HR: 1.5, adjusted 95% CI: 1.1–2.1). Finally, significantly higher expression of miR-4451 in tumors compared to in fresh adjacent normal tissues indicates an oncogenic role of miR-4451 in this tumor. Upregulated miR-4451 in HC samples were frequently found and is significantly associated with advanced stage and poor survival of HC, which may indicate an association of this miRNA with the carcinogenesis process in this tumor site; and they could serve as a prognostic biomarker as well as help develop potential new targets for therapy.     

Outcome Of Implementation Of A Multidisciplinary Team Approach To The Care Of Patients After Transsphenoidal Surgery

Objective: Transsphenoidal surgery (TS) for sellar lesions is an established and safe procedure, but complications can occur, particularly involving the neuroendocrine system. We hypothesized that postoperative care of TS patients would be optimized when performed by a coordinated team including a pituitary neurosurgeon, endocrinologists, and a specialty nurse.Methods: We implemented a formalized, multidisciplinary team approach and standardized postoperative protocols for the care of adult patients undergoing TS by a single surgeon (J.N.B.) at our institution beginning in July 2009. We retrospectively compared the outcomes of 214 consecutive TS-treated cases: 113 cases prior to and 101 following the initiation of the team approach and protocol implementation. Outcomes assessed included the incidence of neurosurgical and endocrine complications, length of stay (LOS), and rates of hospital readmission and unscheduled clinical visits.Results: The median LOS decreased from 3 days preteam to 2 days postteam (P<.01). Discharge occurred on postoperative day 2 in 46% of the preteam group patients compared to 69% of the postteam group (P<.01). Rates of early postoperative diabetes insipidus (DI) and readmissions within 30 days for syndrome of inappropriate antidiuretic hormone (SIADH) or other complications did not differ between groups.Conclusion: Implementation of a multidisciplinary team approach was associated with a reduction of LOS. Despite earlier discharge, postoperative outcomes were not compromised. The endocrinologist is central to the success of this team approach, which could be successfully applied to care of patients undergoing TS, as well as other types of endocrine surgery at other centers.Abbreviations:CSF = cerebrospinal fluidDDAVP = desmopressinDI = diabetes insipidusLOS = length of stayPOD = postoperative daySIADH = syndrome of inappropriate antidiuretic hormoneTS = transsphenoidal surgery     

A Single-Center Open-Label Study To Investigate The Efficacy And Safety Of Repeated Subcutaneous Injections Of Lanreotide Autogel In Patients With Acromegaly Previously Treated With Octreotide

ObjectiveTo evaluate the efficacy of lanreotide Autogel, a depot preparation of a long-acting somatostatin analogue, in patients with acromegaly who were previously treated with octreotide.MethodsIn a prospective single-center, open-label, comparative study, 13 patients were switched from octreotide treatment (baseline) to lanreotide Autogel therapy at a fixed dosage of 90 mg/4 wk. After 6 injections, the dosage was titrated to 60, 90, or 120 mg/4 wk, on the basis of growth hormone (GH) levels, for a further 6 injections. Mean GH and insulinlike growth factor-I (IGF-I) levels were determined at baseline, during treatment (to 48 weeks), and up to 8 weeks after the last injection.ResultsThere was no significant change in the proportion of patients with GH and IGF-I control from baseline to week 48 (GH, 85% to 89%; IGF-I, 46% to 62%). Mean GH levels changed little from baseline, but mean IGF-I levels were significantly lower after 32 weeks (P < .05) and 48 weeks (P < .02). Data collected at 6 and 8 weeks after the last injection suggested that the efficacy of lanreotide Autogel can persist for longer than 4 weeks.ConclusionThis small study suggests that lanreotide Autogel is at least as effective as octreotide in the control of acromegaly and may last for longer than the recommended 4 weeks. It appears to be a useful alternative to long-acting octreotide in the treatment of acromegaly. (Endocr Pract. 2010;16:191-197)     

Short-Term Sitagliptin-Metformin Therapy Is More Effective Than Metformin Or Placebo In Prior Gestational Diabetic Women With Impaired Glucose Regulation

Objective: Our pilot study examined the effectiveness of sitagliptin-metformin (SITA-MET), metformin (MET), and placebo (P) therapy on fasting and post–glucose challenge glucose levels in postpartum women with prior gestational diabetes mellitus (GDM) and impaired glucose regulation.Methods: Prediabetic women (N = 36, age 18 to 42 years) with recent GDM were randomized to P (one pill twice a day), MET (1,000 mg twice a day), or SITA-MET (50 mg SITA, 1,000 mg MET twice a day) for 16 weeks in a single-blind fashion. An individualized diet and exercise plan were provided to all participants. At baseline and 16 weeks, oral glucose tolerance tests were performed to assess glycemia, mean blood glucose (MBG), and calculate insulin sensitivity (IS) and secretion (SI) indexes. Lipid profile, thyroid-stimulating hormone level, and pregnancy test were performed in the baseline sample.Results: Thirty-three (92%) participants completed the study. At study end, 15 participants had normal glycemia (SITA-MET vs. MET, P; P = .035). MBG, IS, IS-SI index, and waist to height ratio were significantly improved with SITA-MET compared with MET and P treatment. SITAMET therapy was more effective in lowering body mass index and waist circumference compared to P treatment.Conclusion: Our pilot study is the first to evaluate the use of a dipeptidyl peptidase 4 inhibitor combined with MET in glucose-impaired women with a history of GDM. In this investigation, combination SITA-MET was found to be superior to MET and P in improving glycemia and metabolic measures in this prediabetic population.Abbreviations: BID = twice a day; BMI = body mass index; BP = blood pressure; BW = body weight; CHOL = cholesterol; DI = disposition index; DM = diabetes mellitus; DPP-4i = dipeptidyl peptidase 4 inhibitor; FBG = fasting blood glucose; GDM = gestational diabetes mellitus; GLP-1 = glucagon-like peptide 1; HDL-C = high-density-lipoprotein cholesterol; HOMA-IR = homeostasis model assessment of insulin resistance; IGI = insulinogenic index; IGR = impaired glucose regulation; IGT = impaired glucose tolerance; IR = insulin resistance; IS = insulin sensitivity; LDL-C = low-density-lipoprotein cholesterol; MBG = mean blood glucose; MET = metformin; OGTT = oral glucose tolerance test; P = placebo; SI = insulin secretion; SI_OGTT = Matsuda's insulin sensitivity index; TRG = triglycerides; WC = waist circumference; WHR = waist to hip ratio; WHtR = waist to height ratio     

No Longterm Severe Thyroid Dysfunction Seen In Patients With Preexisting Reduced Serum Tt3 Concentrations After A Single Large Dose Of Iodinated Contrast

Objective: After an intravenous bolus injection of 100 mL of iodinated contrast agent (370 mgI/mL), the amount of iodine atoms entering the blood is tens of thousands of times the daily dose of iodine recommended by the World Health Organization. However, the effect of iodinated contrast in patients with nonthyroidal illness, manifested as reduced serum total triiodothyronine (TT3) concentrations, is unclear. We studied the effect of iodinated contrast on thyroid function and auto-antibodies in patients with reduced TT3 after diagnosis and treatment of coronary heart disease.Methods: This was a prospective cohort study. One hundred and fifty-four stable angina pectoris patients with reduced TT3 and normal thyroid-stimulating hormone (TSH), free thyroxine (FT4), and reverse triiodothyronine (rT3) were enrolled from January, 2017, to June, 2018. All subjects had no history of thyroid dysfunction and had no recent infections, tumors, trauma, or other critical illnesses. Fourty-one patients underwent coronary angiography and 113 patients underwent coronary intervention.Results: There were 6 patients (3.9%) with hypothyroidism and 30 patients (19.5%) developed subclinical hypothyroidism (SCHypo) on the first day after surgery. There were 6 patients (3.9%) with hypothyroidism, 6 patients (3.9%) with SCHypo, and 18 patients (11.7%) with subclinical hyperthyroidism (SCHyper) at the first month postsurgery. There were 23 patients (14.9%) with SCHyper and 6 patients (3.9%) with SCHypo at the sixth month after surgery. No patient with longterm severe thyroid dysfunction occurred during follow-up. The levels of free triiodothyronine, FT4, TT3, total thyroxine, and TSH showed statistically significant changes at 1 day, and 1, 3, and 6 months postoperative (P<.005). The level of rT3 showed no statistically significant change at 1, 3, and 6 months postoperative (P>.05). The levels of thyroglobulin antibody and thyroid peroxidase antibody decreased at 6 months postoperative (P<.001).Conclusion: The risk of subclinical thyroid dysfunction and transient hypothyroidism occurred with a single large dose of iodinated contrast in the diagnosis and treatment of coronary heart disease, but no longterm severe thyroid dysfunction occurred. Patients with preoperative thyroid antibody elevation were more likely to have subclinical thyroid dysfunction after surgery.Abbreviations: FT3 = free triiodothyronine; FT4 = free thyroxine; PCI = percutaneous coronary intervention; rT3 = reverse triiodothyronine; SCHyper = subclinical hyperthyroidism; SCHypo = subclinical hypothyroidism; TGAB = thyroglobulin antibody; TPOAB = thyroid peroxidase antibody; TT3 = total triiodothyronine; TT4 = total thyroxine; TSH = thyroid-stimulating hormone; WHO = World Health Organization     

Use of a Continuous Glucose Monitoring System in High-Risk Hospitalized Noncritically Ill Patients With Diabetes After Cardiac Surgery and During Their Transition of Care From the Intensive Care Unit During COVID-19: A Pilot Study

ObjectiveContinuous glucose monitoring (CGM) has demonstrated benefits in managing inpatient diabetes. We initiated this single-arm pilot feasibility study during the COVID-19 pandemic in 11 patients with diabetes to determine the feasibility and accuracy of real-time CGM in patients who underwent cardiac surgery and whose care was being transitioned from the intensive care unit.MethodsA Clarke error grid analysis was used to compare CGM and point-of-care measurements. The mean absolute relative difference (MARD) of the paired measurements was calculated to assess the accuracy of CGM for glucose measurements during the first 24 hours on CGM, the remaining time on CGM, and for different chronic kidney disease (CKD) strata.ResultsOverall MARD between point-of-care and CGM measurements was 14.80%. MARD for patients without CKD IV and V with an estimated glomerular filtration rate (eGFR) of ≥20 mL/min/1.73 m² was 12.13%. Overall, 97% of the CGM values were within the no-risk zone of the Clarke error grid analysis. For the first 24 hours, a sensitivity analysis of the overall MARD for all patients and those with an eGFR of ≥20 mL/min/1.73 m² was 15.42% ± 14.44% and 12.80% ± 7.85%, respectively. Beyond the first 24 hours, overall MARD for all patients and those with an eGFR of ≥20 mL/min/1.73 m² was 14.54% ± 13.21% and 11.86% ± 7.64%, respectively.ConclusionCGM has shown great promise in optimizing inpatient diabetes management in the noncritical care setting and after the transition of care from the intensive care unit with high clinical reliability and accuracy. More studies are needed to further assess CGM in patients with advanced CKD.