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Objective:Hypothyroidism is the most common complication of hemithyroidectomy for thyroid nodules. This retrospective cohort study investigated the prognostic factors for hypothyroidism following hemithyroidectomy. Methods:We included patients who underwent hemithyroidectomy between 2016 and 2017, excluding those with history of preoperative hypothyroidism or malignancy on histopathological examination. The primary endpoint was development of hypothyroidism during follow-up (TSH≥2 above normal). Results:Twenty-six of the 128 included patients (20%) developed postoperative hypothyroidism. The following independent prognostic factors were found: preoperative TSH level>1.5 mIU/L (OR 2.11; P=0.013), and remaining thyroid volume adjusted for body surface area<4.0mL/m2(OR 1.77; P=0.015). Twenty-one patients (81%) had first TSH values above the upper limit of normal. Postoperatively, first TSH level correlated significantly with the preoperative value (R=0.5779, P<0.001). Levothyroxine was prescribed to 16% of patients, with a mean dose of 0.92μg/kg/day. Conclusion:Patients with TSH>1.5 mIU/or remaining thyroid volume adjusted for body surface area<4.0mL/m2should have intensified clinical and biological follow-up in the first year after surgery.

AbstractBackground:Addressing the opioid crisis requires an understanding of how to train both health professional students and practicing clinicians on medications for opioid use disorder (mOUD). We designed a robust evaluation instrument to assess the impact of training on perceived clinical knowledge in these different categories of learners. Methods:We enrolled 3rd and 4th year medical, physician assistant (PA), and nurse practitioner (NP) students, as well as practicing PAs, NPs, and physicians to undertake the Drug Addiction Treatment Act (DATA) Waiver Training for mOUD. We designed and implemented a cross-sectional survey to assess perceived change in clinical knowledge as a result of training in opioid use disorder and satisfaction with training. Results:Twenty-one MD/DO and 45 NP/PA students, and 24 practicing MD/DO and 27 NP/PAs completed the survey. Among health professional students (n = 66) and practicing clinicians (n=51), perceived clinical knowledge scores increased significantly (p < 0.001) for all 13 variables. Program evaluation scores for the buprenorphine waiver training were high with no statistical differences between students and practicing clinicians. Overall, the majority of participants indicated they would recommend the training to a colleague (Students’ score = 4.84; practicing clinician scores = 4.53; scale = strongly disagree = 1 to strongly agree = 5). Conclusions:Our novel instrument allowed us to determine that the implementation of buprenorphine waiver trainings for health professional students and practicing clinicians leads to significant increases in perceived knowledge, interest and confidence in diagnosing and treating OUD. Although the buprenorphine waiver can now be obtained without training, many waivered providers still do not prescribe buprenorphine; integrating training into medical, NP, and PA curriculum for students and offering the training to practicing clinicians may increase confidence and uptake of mOUD.

Over the past decade, several strategies have revolutionized the clinical management of patients with cutaneous melanoma (CM), including immunotherapy and targeted tyrosine kinase inhibitor (TKI)-based therapies. Indeed, immune checkpoint inhibitors (ICIs), alone or in combination, represent the standard of care for patients with advanced disease without an actionable mutation. Notably BRAF combined with MEK inhibitors represent the therapeutic standard for disease disclosing BRAF mutation. At the same time, FDG PET/CT has become part of the routine staging and evaluation of patients with cutaneous melanoma. There is growing interest in using FDG PET/CT measurements to predict response to ICI therapy and/or target therapy. While semiquantitative values such as standardized uptake value (SUV) are limited for predicting outcome, new measures including tumor metabolic volume, total lesion glycolysis and radiomics seem promising as potential imaging biomarkers for nuclear medicine. The aim of this review, prepared by an interdisciplinary group of experts, is to take stock of the current literature on radiomics approaches that could improve outcomes in CM.

The aim of this study was to study the feasibility of an SUV-based 177Lu-DOTATATE SPECT/CT quantification and to assess the correlation of different parameters with the corresponding measured on 68Ga-DOTATOC PET/CT in patients with well-differentiated gastroenteropancreatic neuroendocrine tumors (WD-GEP-NET) treated with peptide receptor radionuclide therapy.

Background: Transition to clerkship courses bridge the curricular gap between preclinical and clinical medical education. However, despite the use of simulation-based teaching techniques in other aspects of medical training, these techniques have not been adequately described in transition courses. We describe the development, structure and evaluation of a simulation-based transition to clerkship course. Approach: Beginning in 2012, our institution embarked upon an extensive curricular transformation geared toward competency-based education. As part of this effort, a group of 12 educators designed, developed and implemented a simulation-based transition course. The course curriculum involved seven goals, centered around the 13 Association of American Medical Colleges Core Entrustable Professional Activities for entering residency. Instructional techniques included high-fidelity simulation, and small and large group didactics. Student competency was determined through a simulation-based inpatient-outpatient objective structured clinical examination, with real-time feedback and remediation. The effectiveness of the course was assessed through a mixed methods approach involving pre- and post-course surveys and a focus group. Evaluation: Of 166 students, 152 (91.6%) completed both pre- and post-course surveys, and nine students participated in the focus group. Students reported significant improvements in 21 out of 22 course objectives. Qualitative analysis revealed three key themes: learning environment, faculty engagement and collegiality. The main challenge to executing the course was procuring adequate faculty, material and facility resources. Reflection: This simulation-based, resource-heavy transition course achieved its educational objectives and provided a safe, supportive learning environment for practicing and refining clinical skills.

Smoking increases insulin resistance via multiple mechanisms but is a poorly understood risk factor for onset of type-2 diabetes. It is also associated with impaired beta-cell function in humans, but again the mechanisms are poorly understood. Mechanistic studies of the impact of smoking on carbohydrate metabolism mainly evaluated nicotine as the causal agent, and more rarely other tobacco constituents, making it impossible to conclude that the risk of diabetes is linked to the effects of nicotine alone. Active smoking also has negative impact on glycemic control in both type-1 and type-2 diabetic patients. It increases the risk of all-cause mortality and worsens the chronic complications of diabetes. Impact on microangiopathic complications in type-2 diabetic patients, however, is more controversial. Data on pharmacological and behavioral strategies for smoking cessation used in the general population are more sparse in diabetic patients, despite opportunities with recent therapeutic trials involving varenicline and GLP-1 analogues. It is essential for diabetic patients to stop smoking, and diabetologists must get involved in smoking cessation as they have done for many years in therapeutic education, which can easily include measures to help patients stop smoking.

A 67-year-old man was referred to our department to undergo a 68Ga-DOTATOC PET/CT during the systematic follow-up of a small intestine neuroendocrine tumor. PET revealed an incidental focal increased uptake of 68Ga-DOTATOC matching with a left intraparotid lesion on the combined contrast-enhanced CT, suggestive of a benign salivary tumor. An MRI was performed to characterize this lesion, and finally, the patient underwent surgery. Histological analysis confirmed the presence of a basal cell adenoma.

Peroxisome proliferator-activated receptors (PPARs) are a family of nuclear transcription factors that belong to the steroid receptor superfamily. This family of PPARs includes PPAR[Alpha], PPAR[Delta], PPAR-[Gamma]1, and PPAR[Gamma]2. These PPARs are related to the T3 and vitamin [D.sub.3] receptors and bind to a hexameric direct repeat as a heterodimeric complex with retinoid receptor X[Alpha]. PPARs regulate the expression of a wide array of genes that encode proteins involved in lipid metabolism, energy balance, eicosanoid signaling, cell differentiation, and tumorigenesis. A unique feature of these steroid-like receptors is that the physiologic ligands for PPARs appear to be fatty acids from the n-6 and n-3 families of fatty acids and their respective eicosanoid products. This review describes the characteristics, regulation, and gene targets for PPARs and relates their effects on gene expression to physiologic outcomes that affect lipid and glucose metabolism, thermogenesis, atherosclerosis, and cell differentiation. Am J Clin Nutr 1999;70:566-71.

To evaluate the malignancy rate of focal thyroid incidentaloma (fTI) in a population of patients undergoing a 18F-fluorodeoxyglucose positron emission tomography–computed tomography (FDG PET–CT) for a non-thyroid purpose.We conducted a prospective cohort study from January 2013 to November 2014. All consecutive patients referred for a FDG PET–CT were prospectively screened. Patients with known neoplastic thyroid disease were excluded from the analysis. All patients presenting one or more fTI and who accepted to benefit from a complementary thyroid ultrasonography (US) were included and managed according to the French endocrine society consensus. Prevalence of fTI in our population and malignancy rate was assessed.During the inclusion period, 10,171 patients were referred for a FDG PET–CT in our center. Fifty-three patients presenting a known thyroid disease were excluded. Among the remaining 10,118 patients, 127 (1.3%) with 131 fTI were individualized. US could not be performed in 37 patients. The remaining 90 patients (92 fTI) were explored by US ± fine-needle aspiration biopsy (FNAB). US results demonstrated a nodule aspect in 80 cases of which 60 benefited from FNAB. Nineteen of 92 fTI underwent surgery with 10 malignant lesions among the 60 patients performing both US and FNAB.The prevalence of fTI discovered on FDG PET–CT in our population was 1.3% with 10 malignant lesions among the 60 patients performing both US and FNAB.

Le tabagisme est un facteur de risque de la survenu d’un diabète de type 2 (DT2). Cette constatation a amené à la réalisation de nombreuses études évaluant l’impact du tabagisme sur le métabolisme glucidique. Il est constaté une augmentation de l’insulinorésistance (IR) chez le patient tabagique, pas nécessairement diabétiques, via de multiples mécanismes. Le tabagisme est également associé à une diminution de la fonction β-cellulaire chez l’homme, mais les potentiels mécanismes sont encore mal compris. Les études mécanistiques traitant de l’impact du tabagisme sur le métabolisme glucidique évaluent principalement la nicotine comme agent causal, et plus rarement les autres constituants du tabac, ne permettant pas de conclure que le risque de diabète est lié aux seuls effets de la nicotine. Chez le patient diabétique, le tabagisme actif a également un impact sur l’équilibre glycémique, que ce soit chez les patients diabétiques de type 1 (DT1) ou de type 2 (DT2).

Lipoxygenase (LOX) metabolites from arachidonic acid and linoleic acid have been implicated in atherosclerosis, inflammation, keratinocyte differentiation and tumour progression. We previously showed that peroxisome proliferator-activated receptors (PPARs) play a role in keratinocyte differentiation and that the PPARα ligand 8S-hydroxyeicosatetraenoic acid is important in this process. We hypothesized that blocking LOX activity would block PPAR-mediated keratinocyte differentiation. Three LOX inhibitors, nordihydroguaiaretic acid, quercetin and morin, were studied for their effects on primary keratinocyte differentiation and PPAR activity. All three LOX inhibitors blocked calcium-induced expression of the differentiation marker keratin 1. In addition, activity of a PPAR-responsive element was inhibited in the presence of all three inhibitors, and this effect was mediated primarily through PPARα and PPARγ. LOX inhibitors decreased the activity of a chimaeric PPAR-Gal4-ligand-binding domain reporter system and this effect was reversed by addition of PPAR ligands. Ligand-binding studies revealed that the LOX inhibitors bind directly to PPARs and demonstrate a novel mechanism for these inhibitors in altering PPAR-mediated gene expression.

Although MK886 was originally identified as an inhibitor of 5-lipoxygenase activating protein (FLAP), recent data demonstrate that this activity does not underlie its ability to induce apoptosis [Datta, Biswal and Kehrer (1999) Biochem. J. 340, 371–375]. Since FLAP is a fatty-acid binding protein, it is conceivable that MK886 may affect other such proteins. A family of nuclear receptors that are activated by fatty acids and their metabolites, the peroxisome-proliferator-activated receptors (PPARs), have been implicated in apoptosis and may represent a target for MK886. The ability of MK886 to inhibit PPAR-α, −β and −γ activity was assessed using reporter assay systems (peroxisome-proliferator response element–luciferase). Using a transient transfection system in monkey kidney fibroblast CV-1 cells, mouse keratinocyte 308 cells and human lung adenocarcinoma A549 cells, 10–20μM MK886 inhibited Wy14,643 activation of PPARα by approximately 80%. Similar inhibition of PPARα by MK886 was observed with a stable transfection reporter system in CV-1 cells. Only minimal inhibitory effects were seen on PPARβ and PPARγ. MK886 inhibited PPARα by a non-competitive mechanism as shown by its effects on the binding of arachidonic acid to PPARα protein, and a dose–response study using a transient transfection reporter assay in COS-1 cells. An assay assessing PPAR ligand–receptor interactions showed that MK886 prevents the conformational change necessary for active-complex formation. The expression of keratin-1, a protein encoded by a PPARα-responsive gene, was reduced by MK886 in a culture of mouse primary keratinocytes, suggesting that PPAR inhibition has functional consequences in normal cells. Although Jurkat cells express all PPAR isoforms, various PPARα and PPARγ agonists were unable to prevent MK886-induced apoptosis. This is consistent with MK886 functioning as a non-competitive inhibitor of PPARα, but may also indicate that PPARα is not directly involved in MK886-induced apoptosis. Although numerous PPAR activators have been identified, the results show that MK886 can inhibit PPARα, making it the first compound identified to have such an effect.

We report the case of a 27-year-old woman referred to our department for the characterization of a 7 × 6-cm left ischio-anal fossa mass by Ga-DOTATOC PET/CT. Several diagnoses were previously mentioned, in particular, myxoid sarcoma but also pelvic paraganglioma. Urinary methoxylated derivates and blood chromogranin A tests were negative. PET/CT showed a high Ga-DOTATOC uptake of the mass that was strongly consistent with paraganglioma diagnosis. Histopathological analysis surprisingly revealed a solitary fibrous tumor without aggressive criteria.

A 49-year-old man was referred to our department for an assessment of a cerebral metastasis of unknown primary with 18F-FDG PET/CT. This imaging led to detection of a suspected pulmonary primary carcinoma, as well as an incidental left focal thyroid uptake. An ultrasonography, performed a month later, revealed a thyroiditis aspect. An anti-PD1 immunotherapy was also proposed 2 months later after confirmation of a lung adenocarcinoma. A second baseline FDG PET/CT surprisingly showed a diffuse thyroid uptake. A fine-needle aspiration biopsy of thyroid parenchyma finally revealed a diffuse involvement from lung adenocarcinoma (ie, primary lung metastasis to the thyroid gland).

Vitiligo is a depigmentary disease characterized by melanocyte loss attributed most commonly to autoimmune mechanisms. Currently vitiligo has a high incidence (1% worldwide) but a poor set of treatment options. Piperine, a compound found in black pepper, is a potential treatment for the depigmentary skin disease vitiligo, due to its ability to stimulate mouse epidermal melanocyte proliferation in vitro and in vivo. The present study investigates the use of multispectral imaging and an image processing technique based on local contrast to quantify the stimulatory effects of piperine on human melanocyte proliferation in reconstructed epidermis. We demonstrate the ability of the imaging method to quantify increased pigmentation in response to piperine treatment. The quantization of melanocyte stimulation by the proposed imaging technique illustrates the potential use of this technology to quickly assess therapeutic responses of vitiligo tissue culture models to treatment non-invasively.