Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in diagnosis of pleural effusion of malignant origin

OBJECTIVES: The aim of the present study was to evaluate the diagnostic accuracy of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in differentiating benign from malignant exudative pleural effusions. METHODS: This is a unicentre observational study including 97 consecutive patients with exudative pleural effusions. Metalloproteinase-9, tissue inhibitor of metalloproteinase-1, lactate dehydrogenase, ferritin, carcinoembryonic antigen and carbohydrate antigen 15-3 were measured in pleural effusion and serum by enzyme-linked immunosorbent assay. The activity of metalloproteinase-9 was also evaluated by substrate zymography. The data were correlated with final diagnosis of pleural effusions to evaluate the diagnostic accuracy. RESULTS: Of the 97 eligible patients, 6 were excluded. Of the 91 patients included in the study, 70 had malignant pleural effusions and 21 had benign pleural effusions. Both in sera and pleural effusions, matrix metalloproteinase-9 (P < 0.0001), tissue inhibitor of metalloproteinase-1 (P < 0.0001) and carcinoembryonic antigen (P < 0.0001) levels were higher in neoplastic patients than in benign group. Zymography analysis showed a most prominent band at a molecular weight of 92 kDa (metalloproteinase-9) whereas a less intense band was observed at 72 kDa (metalloproteinase-2). A significant correlation was found between metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels in pleural effusion (P < 0.0001; r = 0.8) and serum (P < 0.03; r = 0.2). Pleural effusion metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed higher value of sensitivity (97 and 91%, respectively) and specificity (90 and 95%, respectively) compared with other standard markers. Serum metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 levels showed similar results. Among 70 neoplastic patients, 29 had negative pleural cytology. Of these, 25 presented elevated levels of metalloproteinase-9 and tissue inhibitor of metalloproteinase-1, whereas 4 patients had elevated levels of one of the two markers. CONCLUSIONS: Our results showed that metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 might be valuable markers in differentiating benign from malignant pleural effusions. Their levels are neither influenced by the histology and tumour origin nor by the presence of tumour cells in pleural effusions. Thus, their use in clinical practice could help in the selection of patients needing more invasive procedures, such as thoracoscopic biopsy

Forensic textile damage analysis: Practical issues and methodological perspectives

Clothing damage analysis is an important tool for forensic investigations and, even it is a niche field, it is gaining interest. Moreover, the attention is shifting from evaluating just the “biological” traces found on the clothes to the modifications that clothes themselves undergo in the context of a specific traumatic dynamic. The Authors analyze a case of the investigation on a hole in the jacket worn by the victim when he was attacked, performed through optical microscope and morphological and elemental SEM/EDX analysis, to determine the origin of this texture damage to verify a witness story

Natural History and Management of Familial Paraganglioma Syndrome Type 1: Long-Term Data from a Large Family

Head and neck paragangliomas are the most common clinical features of familial paraganglioma syndrome type 1 caused by succinate dehydrogenase complex subunit D (SDHD) mutation. The clinical management of this syndrome is still unclear. In this study we propose a diagnostic algorithm for SDHD mutation carriers based on our family case series and literature review. After genetic diagnosis, first evaluation should include biochemical examination and whole-body imaging. In case of lesion detection, nuclear medicine examination is required for staging and tumor characterization. The study summarizes the diagnostic accuracy of different functional imaging techniques in SDHD mutation carriers. 18F-3,4-dihydroxyphenylalanine (18F-DOPA) positron emission tomography (PET)-computed tomography (CT) is considered the gold standard. If it is not available, 123I-Metaiodobenzylguanidine (MIBG) could be used also for predicting response to radiometabolic therapy. 18F-fluoro-2-deoxy-D-glucose (18F-FDG) PET-CT has a prognostic role since high uptake identifies more aggressive cases. Finally, 68Ga-peptides PET-CT is a promising diagnostic technique, demonstrating the best diagnostic accuracy in our and in other published case series, even if this finding still needs to be confirmed in larger studies. Periodic follow-up should consist of annual biochemical and ultrasonographic screening and biannual magnetic resonance examination to identify biochemical silent tumors early

Taste Perception And Food Choices

OBJECTIVES: The extent to which variation in taste perception influences food preferences is, to date, controversial. Bitterness in food triggers an innate aversion that is responsible for dietary restriction in children. We investigated the association among genetic variations in bitter receptor TAS2R38 and food choices in healthy children in the Mediterranean area, to develop appropriate tools to evaluate the relation among genetic predisposition, dietary habits, and feeding disorders. The aims of the study were to get a first baseline picture of taste sensitivity in healthy adults and their children and to explore taste sensitivity in a preliminary sample of obese children and in samples affected by functional gastrointestinal diseases. METHODS: Individuals (98 children, 87 parents, 120 adults) were recruited from the general population in southern Italy. Bitterness sensitivity was assessed by means of a suprathreshold method with 6-propyl-2-thiouracil. Genomic DNA from saliva was used to genotype individuals for 3 polymorphisms of TAS2R38 receptor, A49P, A262 V, and V296I. Food intake was assessed by a food frequency questionnaire. RESULTS: Children's taste sensation differed from that of adults: we observed a higher frequency of supertasters among children even in the mother-child dyads with the same diplotypes. Among adults, supertaster status was related with proline-alanine-valine (taster allele) homozygous haplotype, whereas supertaster children were mainly heterozygous. Regarding the food choices, we found that a higher percentage of taster children avoided bitter vegetables or greens altogether compared with taster adults. Taster status was also associated with body mass index in boys. CONCLUSIONS: Greater sensitivity to 6-propyl-2-thiouracil predicts lower preferences for vegetables in children, showing an appreciable effect of the genetic predisposition on food choices. None of the obese boys was a supertaster

Central and Peripheral Nervous System Complications of Vasculitis Syndromes From Pathology to Bedside: Part 1—Central Nervous System

Purpose of Review: The aim of this review is to provide a comprehensive update on the clinical assessment, diagnosis, complications, and treatment of primary central nervous system vasculitis (PCNSV). Recent Findings: The developments in neuroimaging, molecular testing, and cerebral biopsy have enhanced clinical assessment and decision making, providing novel insights to prevent misdiagnosis increasing diagnostic certainty. Advances in imaging techniques visualizing the wall of intracranial vessels have improved the possibility to distinguish inflammatory from non-inflammatory vascular lesions. Large recent studies have revealed a more varied histopathological pictures and disclosed an association with amyloid angiopathy. Unfortunately, therapy remains largely empiric. Summary: PCNSV is a heterogeneous group of disorders encompassing different clinical subsets that may differ in terms of prognosis and therapy. Recent evidence has described a more benign course, with good response to therapy. New diagnostic techniques will play soon a pivotal role in the appropriate diagnosis and prompt management of PCNSV

Risk management and recommendations for the prevention of fatal foreign body aspiration: Four cases aged 1.5 to 3 years and mini-review of the literature

(1) Background: Foreign body aspiration (FBA) is a significant public health concern among the pediatric population, and fatalities are dramatic for families. It typically involves organic foreign bodies (mainly food) aspirated by children under three years old, usually at home or school. This review aimed to focus on the preventive measures around four actual cases of fatal foreign body aspiration, emphasizing the correct execution of the Heimlich maneuver and cardiopulmonary resuscitation, supervised mealtimes, and high-risk foods. (2) Methods: Four fatal cases of foreign body aspiration in children are presented here. The children were in a free environment, such as school, home, and the countryside, and were in the presence of teachers, parents, and a grandmother who did not supervise the children adequately. A literature review was performed via the MEDLINE database using the key terms: “foreign body aspiration,” “infant choking, 1.5 to 3 years,” “food and foreign body aspiration,” “common household,” “prevention of foreign body aspiration,” “guidelines,” “recommendations,” “training of caregivers (parents, educators),” “resuscitation,” “Heimlich maneuver,” and “disengagement of the upper airways.” We focused on the prevention of foreign body aspiration. (3) Results: a complete postmortem examination was performed. In three cases, the foreign bodies were food (mozzarella cheese, pear, or raw bean), while in one case, the foreign body was a pebble. (4) Conclusions: This review aimed to discuss recent scientific literature and provide a perspective on the benefits of a dedicated approach to the management of fatal foreign body aspiration in children by caregivers who usually have no experience with the best ways of supervising children in a safe environment, especially regarding the correct execution of resuscitation maneuvers, such as the Heimlich maneuver. Recommendation updates could improve healthcare quality in a pediatric setting and reduce medico-legal implications

Covid-19 pandemic and equal access to vaccines

The COVID-19 pandemic has evidenced the chronic inequality that exists between populations and communities as regards global healthcare. Vaccination, an appropriate tool for the prevention of infection, should be guaranteed by means of proportionate interventions to defeat such inequality in populations and communities affected by a higher risk of infection. Equitable criteria of justice should be identified and applied with respect to access to vaccination and to the order in which it should be administered. This article analyzes, as regards the worldwide distribution of anti-COVID-19 vaccines, the various ways the principle of equity has been construed and applied or even overlooked. The main obstacle to equal access to vaccines is vaccine nationalism. The perception of equity varies with the differing reference values adopted. Adequate response to needs appears to be the principal rule for achieving the criterion of equity in line with distributive justice. Priorities must be set equitably based on rational parameters in accordance with current needs. The entire process must be governed by transparency, from parameter identification to implementation. The issue of equal access to vaccination affects the entire world population, necessitating specific protective interventions. In light of this, the World Health Organization (WHO) has devised the COVAX plan to ensure that even the poorest nations of the world receive the vaccine; certain initiatives are also supported by the European Union (EU). This pandemic has brought to the fore the need to build a culture of equitable relationships both in each country's own domain and with the rest of the world

Cytokines and VEGF Induction in Orthodontic Movement in Animal Models

Orthodontics is a branch of dentistry that aims at the resolution of dental malocclusions. The specialist carries out the treatment using intraoral or extraoral orthodontic appliances that require forces of a given load level to obtain a tooth movement in a certain direction in dental arches. Orthodontic tooth movement is dependent on efficient remodeling of periodontal ligament and alveolar bone, correlated with several biological and mechanical responses of the tissues surrounding the teeth. A periodontal ligament placed under pressure will result in bone resorption whereas a periodontal ligament under tension results in bone formation. In the primary stage of the application of orthodontic forces, an acute inflammation occurs in periodontium. Several proinflammatory cytokines are produced by immune-competent cells migrating by means of dilated capillaries. In this paper we summarize, also through the utilization of animal models, the role of some of these molecules, namely, interleukin-1β and vascular endothelial growth factor, that are some proliferation markers of osteoclasts and osteoblasts, and the macrophage colony stimulating factor

Laryngeal neuroendocrine tumor with elevated serum calcitonin: a diagnostic and therapeutic challenge. Case report and review of literature

Introduction: Laryngeal neuroendocrine neoplasms (NENs) are a rare group of NENs of the neck, which commonly show immunostaining for calcitonin. Laryngeal NENs with calcitonin hypersecretion and lymph node metastases represent a diagnostic and therapeutic challenge, which should be included in the differential diagnosis of medullary thyroid carcinoma (MTC). We report a complex case of laryngeal NEN with calcitonin hypersecretion and a review of the literature. Case Presentation: A 59-year-old man presented with dysphagia, dyspnea, and lateral cervical mass; he was a smoker. At first imaging, a laryngeal lesion with lateral cervical lymphadenopathies was found, and it resulted as a moderately differentiated neuroendocrine tumor (G2), Ki67 = 5%, positive for calcitonin. Increased levels of serum calcitonin (50 pg/ml) were found. The patient started somatostatin analogs for lesions positivity to somatostatin receptor-based imaging. After 5 months, the disease progressed at 18F-fluorodeoxyglucose (18F-FDG) PET-CT, and also new painful cutaneous lesions occurred. Considering high serum levels of calcitonin, differential diagnosis with MTC was required. Patient performed a thyroid color Doppler ultrasound, nodule fine needle aspiration, calcitonin dosage in fine needle washout fluid, and a calcium gluconate stimulation test. After multidisciplinary evaluation, we decided to perform a total thyroidectomy associated with lateral cervical lymphadenectomy and resection of skin metastases. No MTC was found. Two of the five resected lymph nodes, left upper parathyroid, and skin lesions were metastases of NEN G2, positive for calcitonin. After 2 months, new painful skin lesions occurred, and a target therapy with everolimus 10 mg/day was started. After 6 months of therapy, partial metabolic response with a reduction of 53.7% of radiotracer uptake at primary tumor was detected together with an improvement of patient's quality of life. Conclusions: The present case is the seventh described in the literature of laryngeal NEN associated with elevated serum calcitonin levels and the first case with parathyroid metastasis, suggesting the importance of a correct differential diagnosis between MTC and calcitonin-secreting laryngeal NEN, using an integrated approach of biochemistry and advanced imaging. This is also the first time that somatostatin analogs and then everolimus were used in this setting, resulting in clinical and partial metabolic response