Total thyroidectomy associated to chemotherapy in primary squamous cell carcinoma of the thyroid

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignant disease with rapid fatal prognosis. The onset is generally characterized by sudden bilateral latero-cervical lymphadenopathy. The Authors report patient of 58-year-old who referred for evaluation of rapidly aggravating bilateral latero-cervical lymphadenopathy. The US highlighted the presence of a hypoechoic nodular lesion characterized by peri and intra-nodular vascularization. Multilayer CT showed diffused involvement of mediastinal and bilateral latero-cervical lymph nodes, with no evidence of primary pulmonary neoplasia or elsewhere. The patient underwent total thyroidectomy. The peri-isthmic tissue was removed due to the presence of a small roundish formation, that was due to lymph node metastasis at histological examination. Histological diagnosis: PSCCT. The immunohistochemical panel of the thyroid lesion was indispensable for the differential diagnosis between PSCCT, medullary carcinoma, anaplastic carcinoma, and thyroid metastasis of neoplasia with unknown primitiveness. The patient underwent chemotherapeutic treatment with Carboplatin and Paclitaxel with modest improvement of dysphagia symptoms and reduction of 10-15% of the target lesions. The clinical course was characterized by loco-regional progression of the disease with exitus in 10 months after diagnosis. Survival and quality of life after surgical therapy and chemotherapy were like that of patients undergoing only chemotherapy. Due to the extreme rarity of the neoplasia, 60 cases described in Literature, no exclusive guidelines are reported for PSCCT. More extensive case studies are needed to evaluate the effects of total thyroidectomy with intent R0/R1 on improving survival and quality of life of patients with PSCCT

c-Maf Transcription Factor Regulates ADAMTS-12 Expression in Human Chondrogenic Cells.

ObjectiveADAMTS (a disintegrin and metalloproteinase with thrombospondin type-1 motif) zinc metalloproteinases are important during the synthesis and breakdown of cartilage extracellular matrix. ADAMTS-12 is up-regulated during in vitro chondrogenesis and embryonic limb development; however, the regulation of ADAMTS-12 expression in cartilage remains unknown. The transcription factor c-Maf is a member of Maf family of basic ZIP (bZIP) transcription factors. Expression of c-Maf is highest in hypertrophic chondrocytes during embryonic development and postnatal growth. We hypothesize that c-Maf and ADAMTS-12 are co-expressed during chondrocyte differentiation and that c-Maf regulates ADAMTS-12 expression during chondrogenesis.DesignPromoter analysis and species alignments identified potential c-Maf binding sites in the ADAMTS-12 promoter. c-Maf and ADAMTS-12 co-expression was monitored during chondrogenesis of stem cell pellet cultures. Luciferase expression driven by ADAMTS-12 promoter segments was measured in the presence and absence of c-Maf, and synthetic oligonucleotides were used to confirm specific binding of c-Maf to ADAMTS-12 promoter sequences.ResultsIn vitro chondrogenesis from human mesenchymal stem cells revealed co-expression of ADAMTS-12 and c-Maf during differentiation. Truncation and point mutations of the ADAMTS-12 promoter evaluated in reporter assays localized the response to the proximal 315 bp of the ADAMTS-12 promoter, which contained a predicted c-Maf recognition element (MARE) at position -61. Electorphoretic mobility shift assay confirmed that c-Maf directly interacted with the MARE at position -61.ConclusionsThese data suggest that c-Maf is involved in chondrocyte differentiation and hypertrophy, at least in part, through the regulation of ADAMTS-12 expression at a newly identified MARE in its proximal promoter

Cartilage Oligomeric Matrix Protein (COMP): A Biomarker of Arthritis

Arthritis is a chronic disease with a significant impact on the population. It damages the cartilage, synovium, and bone of the joints causing pain, impairment, and disability in patients. Current methods for diagnosis of and monitoring the disease are only able to detect clinical manifestations of arthritis late in the process. However, with the recent onset of successful treatments for rheumatoid arthritis and osteoarthritis, it becomes important to identify prognostic factors that can predict the evolution of arthritis. This is especially critical in the early phases of disease so that these treatments can be started as soon as possible to slow down progression of the disease. A valuable approach to monitor arthritis would be by measuring biological markers of cartilage degradation and repair to reflect variations in joint remodeling. One such potential biological marker of arthritis is cartilage oligomeric matrix protein (COMP). In various studies, COMP has shown promise as a diagnostic and prognostic indicator and as a marker of the disease severity and the effect of treatment. This review highlights the progress in the utilization of COMP as a biomarker of arthritis

The contribution of specific non-communicable diseases to the achievement of the Sustainable Development Goal 3.4 in Peru

Background Non-communicable diseases (NCDs) have received political attention and commitment, yet surveillance is needed to measure progress and set priorities. Building on global estimates suggesting that Peru is not on target to meet the Sustainable Development Goal 3.4, we estimated the contribution of various NCDs to the change in unconditional probability of dying from NCDs in 25 regions in Peru. Methods Using national death registries and census data, we estimated the unconditional probability of dying between ages 30 and 69 from any and from each of the following NCDs: cardiovascular, cancer, diabetes, chronic respiratory diseases and chronic kidney disease. We estimated the contribution of each NCD to the change in the unconditional probability of dying from any of these NCDs between 2006 and 2016. Results The overall unconditional probability of dying improved for men (21.4%) and women (23.3%). Cancer accounted for 10.9% in men and 13.7% in women of the overall reduction; cardiovascular diseases also contributed substantially: 11.3% in men) and 9.8% in women. Consistently in men and women and across regions, diabetes moved in the opposite direction of the overall reduction in the unconditional probability of dying from any selected NCD. Diabetes contributed a rise in the unconditional probability of 3.6% in men and 2.1% in women. Conclusions Although the unconditional probability of dying from any selected NCD has decreased, diabetes would prevent Peru from meeting international targets. Policies are needed to prevent diabetes and to strengthen healthcare to avoid diabetes-related complications and delay mortality

Cyathostomine egg reappearance period following ivermectin treatment in a cohort of UK Thoroughbreds.

Background: In spite of the emergence of populations of drug-resistant cyathostomins worldwide, little is known of parasite species responsible for 'early egg shedding' in cohorts of horses subjected to treatment with widely used anthelmintics (e.g. ivermectin [IVM]). In this study, we determined the cyathostomin egg reappearance period (ERP) after IVM treatment of a cohort of yearlings from a large Thoroughbred (TB) stud farm in the United Kingdom, and identified species of IVM-'resistant' cyathostomins using a combination of fundamental parasitology techniques coupled with advanced molecular tools. Methods: Individual faecal samples were collected from TB yearlings with cyathostomin infection prior to IVM treatment, as well as at 2, 14, 21, 28, 35, 42 and 49 days posttreatment. Faecal egg counts (FEC) were performed for each individual sample for determination of ERPs. In addition, individual larval cultures were performed and representative numbers of third stage larvae (L3s) harvested from each culture were subjected to molecular species identification via PCR-Reverse Line Blot (RLB). Results: Prior to IVM treatment, 11 cyathostomin species were detected in faecal samples from TB horses enrolled in this study, i.e. Cyathostomum (Cya.) catinatum, Cylicostephanus (Cys.) longibursatus, Cys. goldi, Cylicocyclus (Cyc.) nassatus, Cys. calicatus, Cya, pateratum, Cyc. radiatus, Paraposteriostomum mettami, Coronocyclus (Cor.) labratus, Cyc. insigne and Cyc. radiatus variant A. Of these, eggs of Cya. catinatum, Cys. longibursatus, Cyc. nassatus and Cyc. radiatus could be detected at 28 days post-treatment, while from day 42 onwards, cyathostomin species composition reflected data obtained pre-IVM treatment, with the exception of eggs of Cor. labratus and Cyc. insigne that could no longer be detected post-IVM administration. Conclusions: This study provides valuable data on the occurrence of IVM-resistance in cyathostomins in the UK. Nevertheless, further investigations are needed to shed light on the prevalence and incidence of drug-resistance in this country as well as other areas of the world where equine trade is substantial

Evaluating equality in prescribing Novel Oral Anticoagulants (NOACs) in England: the protocol of a Bayesian small area analysis

Background Atrial fibrillation (AF) is the most common cardiac arrhythmia, affecting about 1.6% of the population in England. Novel oral anticoagulants (NOACs) are approved AF treatments that reduce stroke risk. In this study, we estimate the equality in individual NOAC prescriptions with high spatial resolution in Clinical Commissioning Groups (CCGs) across England from 2014 to 2019. Methods A Bayesian spatio-temporal model will be used to estimate and predict the individual NOAC prescription trend on ‘prescription data’ as an indicator of health services utilisation, using a small area analysis methodology. The main dataset in this study is the “Practice Level Prescribing in England,” which contains four individual NOACs prescribed by all registered GP practices in England. We will use the defined daily dose (DDD) equivalent methodology, as recommended by the World Health Organization (WHO), to compare across space and time. Four licensed NOACs datasets will be summed per 1,000 patients at the CCG-level over time. We will also adjust for CCG-level covariates, such as demographic data, Multiple Deprivation Index, and rural-urban classification. We aim to employ the extended BYM2 model (space-time model) using the RStan package. Discussion This study suggests a new statistical modelling approach to link prescription and socioeconomic data to model pharmacoepidemiologic data. Quantifying space and time differences will allow for the evaluation of inequalities in the prescription of NOACs. The methodology will help develop geographically targeted public health interventions, campaigns, audits, or guidelines to improve areas of low prescription. This approach can be used for other medications, especially those used for chronic diseases that must be monitored over time