COVID-19 Pandemic and Head and Neck Surgery Residency Program: Proposals for the "Phase 2"

n/

Impact of the COVID-19 Pandemic on Otolaryngology Residency: A Real-Life Experience

The coronavirus disease (COVID-19) pandemic as been rapidly spreading worldwide. In our country, the entire Italian Healthcare System has been forced to adapt to this unprecedented condition in this century. The Head and Neck Department clinical and surgical activity was substantially reduced. In this situation, the Ear, Nose and Throat (ENT) residents in University Hospitals find themselves in an uncertain position; we are physicians, facing a deadly disease about which much remains unknown, but we are also trainees, and there is a high risk for our residency training to be affected. With this Letter, we would like to give a testimony of our experience and give some advices to bridge the training gap

Pleomorphic adenoma of the parotid gland and ipsilateral thyroid incidentaloma: report of a rare case with review of literature

Background: Pleomorphic adenomas are benign tumors of the salivary glands that mainly affect the lower pole of the superficial lobe of the parotid gland. The term "pleomorphic" refers to the epithelial and connective origin of the mass. The clinical presentation is typically that of asymptomatic swelling which increases in volume. Therapy consists in surgical removal of the tumor mass by parotidectomy with nerve preservation. Case details: This clinical case describes an interesting case of pleomorphic adenoma of the parotid gland in a 62-year-old patient. The patient presented with a long history of an asymptomatic mildly worsening swelling of the left parotid region. The peculiarity of the clinical case is the dimension of the adenoma (9x5x9 cm) and the presence of a thyroid incidentaloma (TI), consisting of a thyroid multinodular goiter composed of nodules, the largest of which measured 8 cm in diameter. This mass dislocated the laryngotracheal axis, compressed the larynx and caused the reduction of the respiratory space, making orotracheal intubation difficult and determining the need to perform a tracheotomy. Conclusion: Benign pleomorphic adenomas can potentially reach large sizes if untreated. Socio-economic problems may be the reason for late diagnosis

Clinical significance of circulating tumor cells and cell-free DNA in pediatric rhabdomyosarcoma

Liquid biopsy analysis represents a powerful and noninvasive tool to uncover biomarkers for disseminated disease assessment and longitudinal monitoring of patients. Herein, we explored the value of circulating and disseminated tumor cells (CTC and DTC, respectively) and cell-free DNA (cfDNA) in pediatric rhabdomyosarcoma (RMS). Peripheral blood and bone marrow samples were analyzed to detect and enumerate CTC and DTC, respectively. We used the epithelial cellular adhesion molecule (EpCAM)-based CellSearch platform coupled with an automatic device to collect both EpCAM-positive and EpCAM-low/negative CTCs. The standard assay was implemented, including the mesenchymal marker desmin. For selected cases, we molecularly profiled primary tumors and liquid biopsy biomarkers using whole-exome sequencing and droplet digital PCR, respectively. RMS patients with metastatic disease had a significantly higher number of CTCs compared to those with localized disease, whereas DTCs were detected independently of disease presentation. The use of the desmin marker remarkably increased the identification of CTCs and DTCs in RMS samples. Of note, CTC clusters were detected in RMS patients with disseminated disease. Further, cfDNA and CTC molecular features closely reflected the molecular makeup of primary tumors and informed of disease course

Design, synthesis, binding, and molecular modeling studies of new potent ligands of cannabinoid receptors

In our ongoing program aimed at the design, synthesis, and biological evaluation of novel cannabinoid receptor ligands derived from olivetol and hexyl-resorcinol, we have designed a structural model for new derivatives on the basis of a previous study. Here we report the synthesis, binding, and molecular modeling studies of new potent compounds with high affinity toward CB(1) and CB(2) receptors. Compounds with amidic 'heads' with alkyloxy chains varying in length from 8 to 12 carbon atoms showed nanomolar affinity for both receptors, depending on the type of aromatic backbone. Two of the new compounds, although not very potent, exhibit selectivity for CB(1) receptors (CB(1)/CB(2)=0.07 and 0.08, respectively). Molecular modeling studies fitted this new class of cannabinoid ligands into a CB(1) receptor model, and the qualitative analysis of the results was in general agreement with the CB(1) affinity constants observed experimentally for these derivatives

Role of the Specialized Proresolving Mediator Resolvin D1 in Systemic Lupus Erythematosus: Preliminary Results

Objective. Systemic lupus erythematosus (SLE) is an autoimmune systemic disease and its pathogenesis has not yet been completely clarified. Patients with SLE show a deranged lipid metabolism, which can contribute to the immunopathogenesis of the disease and to the accelerated atherosclerosis. Resolvin D1 (RvD1), a product of the metabolism of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA), acts as a specialized proresolving mediator which can contribute in restoring the homeostasis in inflamed tissues. The aim of the present pilot study is to evaluate plasma levels of RvD1 in patients with SLE and healthy subjects, investigating its potential role as a biomarker of SLE and assessing its relationship with disease activity and laboratory parameters. Methods. Thirty patients with SLE and thirty age- and sex-matched healthy subjects (HSs) have been consecutively recruited at Campus Bio-Medico University Hospital. RvD1 plasma levels were measured by ELISA according to the manufacturer’s protocol (Cayman Chemical Co.). RvD1 levels were compared using Mann–Whitney test. Discriminatory ability for SLE has been evaluated by the area under the ROC curve. Results. Lower levels of RvD1, 45.6 (35.5–57.4) pg/ml, in patients with SLE have been found compared to HSs, 65.1 (39.43–87.95) pg/ml (p=0.0043). The area under the ROC curve (AUC) for RvD1 was 0.71 (95% CI: 0.578–0.82) and the threshold value of RvD1 for the classification of SLE was <58.4 pg/ml, sensitivity 80% (95% CI: 61.4–92.3), and specificity 63.3% (95% CI: 43.9–80.1), likelihood ratio 2.2 (95% CI: 1.3–3.6). Conclusions. The present preliminary study allows hypothesizing a dysregulation of RvD1 in patients with SLE, confirming the emerging role of bioactive lipids in this disease

Urinary Metabolomics in Pediatric Obesity and NAFLD Identifies Metabolic Pathways/Metabolites Related to Dietary Habits and Gut-Liver Axis Perturbations.

To get insight into still elusive pathomechanisms of pediatric obesity and non-alcoholic fatty liver disease (NAFLD) we explored the interplay among GC-MS studied urinary metabolomic signature, gut liver axis (GLA) abnormalities, and food preferences (Kid-Med). Intestinal permeability (IP), small intestinal bacterial overgrowth (SIBO), and homeostatic model assessment-insulin resistance were investigated in forty children (mean age 9.8 years) categorized as normal weight (NW) or obese (body mass index &lt;85th or &gt;95th percentile, respectively) ± ultrasonographic bright liver and hypertransaminasemia (NAFLD). SIBO was increased in all obese children (p = 0.0022), IP preferentially in those with NAFLD (p = 0.0002). The partial least-square discriminant analysis of urinary metabolome correctly allocated children based on their obesity, NAFLD, visceral fat, pathological IP and SIBO. Compared to NW, obese children had (1) higher levels of glucose/1-methylhistidine, the latter more markedly in NAFLD patients; and (2) lower levels of xylitol, phenyl acetic acid and hydroquinone, the latter especially in children without NAFLD. The metabolic pathways of BCAA and/or their metabolites correlated with excess of visceral fat centimeters (leucine/oxo-valerate), and more deranged IP and SIBO (valine metabolites). Urinary metabolome analysis contributes to define a metabolic fingerprint of pediatric obesity and related NAFLD, by identifying metabolic pathways/metabolites reflecting typical obesity dietary habits and GLA perturbations

Salivary markers of hepato-metabolic comorbidities in pediatric obesity

Background: The pediatric obesity epidemic calls for the noninvasive detection of individuals at higher risk of complications. Aims: To investigate the diagnostic role of combined salivary uric acid (UA), glucose and insulin levels to screen noninvasively for metabolic syndrome (MetS) and nonalcoholic fatty liver disease. Methods: Medical history, clinical, anthropometric, and laboratory data including serum triglyceride, glucose, insulin, HOMA, HDL-cholesterol, and UA levels of 23 obese children (15 with [St+] and 8 without [St−] ultrasonographic hepatic steatosis) and 18 normal weight controls were considered. Results: Serum and salivary UA (p &lt; 0.05; R 2 = 0.51), insulin (p &lt; 0.0001; R 2 = 0.79), and HOMA (p &lt; 0.0001; R 2 = 0.79) levels were significantly correlated; however their values tended to be only slightly higher in the obese patients, predominately in [St+], than in the controls. Notably, UA and insulin levels in both fluids increased in parallel to the number of MetS components. After conversion of the z-logit function including salivary/anthropometric parameters in a stepwise logistic regression analysis, a factor of 0.5 allowed for predicting hepatic steatosis with high sensitivity, specificity, and total accuracy. Conclusions: Salivary testing together with selected anthropometric parameters helps to identify noninvasively obese children with hepatic steatosis and/or having MetS components

Metabolomic salivary signature of pediatric obesity related liver disease and metabolic syndrome

Pediatric obesity-related metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are increasingly frequent conditions with a still-elusive diagnosis and low-efficacy treatment and monitoring options. In this study, we investigated the salivary metabolomic signature, which has been uncharacterized to date. In this pilot-nested case-control study over a transversal design, 41 subjects (23 obese patients and 18 normal weight (NW) healthy controls), characterized based on medical history, clinical, anthropometric, and laboratory data, were recruited. Liver involvement, defined according to ultrasonographic liver brightness, allowed for the allocation of the patients into four groups: obese with hepatic steatosis ([St+], n = 15) and without hepatic steatosis ([St–], n = 8), and with (n = 10) and without (n = 13) MetS. A partial least squares discriminant analysis (PLS-DA) model was devised to classify the patients’ classes based on their salivary metabolomic signature. Pediatric obesity and its related liver disease and metabolic syndrome appear to have distinct salivary metabolomic signatures. The difference is notable in metabolites involved in energy, amino and organic acid metabolism, as well as in intestinal bacteria metabolism, possibly reflecting diet, fatty acid synthase pathways, and the strict interaction between microbiota and intestinal mucins. This information expands the current understanding of NAFLD pathogenesis, potentially translating into better targeted monitoring and/or treatment strategies in the future

Liquid Biopsy in Pediatric Renal Cancer: Stage I and Stage IV Cases Compared

Pediatric renal cancer is rare, and robust evidence for treatment recommendations is lacking. In the perspective of personalized medicine, clinicians need new biomarkers to improve risk stratification and patients&rsquo; follow-up. Herein, we analyzed some liquid biopsy tools, which have been never tested in pediatric renal cancer: namely, circulating tumor cells (CTCs); the expression of M30, an apoptosis marker, to test CTC metastatic potential; and c-MET expression in CTCs, because of its role in renal cancer progression and drug-resistance. Furthermore, we evaluated the Circulating Endothelial Cells (CECs), whose utility we previously demonstrated in adult metastatic renal cancer treated with anti-angiogenic therapy. We compared two renal cell carcinomas of clear-cell type, stage I and IV, which underwent surgery and surgery plus Sunitinib, respectively. Baseline CTC level and its changes during follow-up were consistent with patients&rsquo; outcome. In case 2, stage IV, the analysis of CECs performed during Sunitinib revealed a late response to treatment consistent with poor outcome, as the finding of M30-negative, viable cells. Noteworthily, few CTCs were MET-positive in both cases. Our study highlights the feasibility for a change in the prognostic approach and follow-up of childhood renal cancer, with a view to guide a better treatment design