Introduction Thymomas and thymic carcinoma (TC) are the most common neoplasms localised in the thymus. These diseases are poorly understood, but progress made in next-generation sequencing (NGS) ...technology has provided novel data on their molecular pathology. Material and methods Genomic DNA was isolated from formalin-fixed paraffin- embedded tumour tissue. We investigated somatic variants in 35 thymoma patients using amplicon-based TruSeq Amplicon Cancer Panel (TSACP) that covers 48 cancer related genes. We also analysed three samples from healthy individuals by TSACP platform and 32 healthy controls using exome sequencing. Results The total number of detected variants was 4447, out of which 2906 were in the coding region (median per patient 83, range: 2–300) and 1541 were in the non-coding area (median per patient 44, range: 0–172). We identified four genes, APC, ATM, ERBB4, and SMAD4, having more than 100 protein-changing variants. Additionally, more than 70% of the analysed cases harboured protein-changing variants in SMAD4, APC, ATM, PTEN, KDR, and TP53. Moreover, this study revealed 168 recurrent variants, out of which 15 were shown to be pathogenic. Comparison to controls revealed that the variants we reported in this study were somatic thymoma-specific variants. Additionally, we found that the presence of variants in SMAD4 gene predicted shorter overall survival in thymoma patients. Conclusions The most frequently mutated genes in thymoma samples analysed in this study belong to the EGFR, ATM, and TP53 signalling pathways, regulating cell cycle check points, gene expression, and apoptosis. The results of our study complement the knowledge of thymoma molecular pathogenesis.
A 69-year-old woman presented with severe anemia, proteinuria, microscopic hematuria and rapidly progressive renal failure. She was admitted to the nephrology department due to severe deterioration ...of renal function with complaints of malaise, fever, dry cough and occasional epistaxis that appeared 2 months prior to admission. Histopathologic examination of a specimen from kidney biopsy and immunologic findings revealed ANCA positive pauci-immune crescentic glomerulonephritis. The patient had a history of ovarian granulosa cell tumor and lung metastases that were treated surgically with postoperative radiotherapy and chemotherapy. Thoracic computed tomography showed tissue neoplasm in the right lung and ultrasound-guided percutaneous transthoracic biopsy confirmed granulosa cell tumor. That was a relapse, thirty-nine years after initial treatment of malignant disease and twenty-four years after surgical resection of metastases from both lungs. Although the association between malignancy and vasculitis has been well known for decades, this is the first described case of ANCA vasculitis associated with any type of gynecological malignancy and glomerulonephritis.
Nonspecific interstitial pneumonia (NSIP) is often associated with connective tissue diseases (CTD). The diagnosis of NSIP was confirmed in a 63-year-old man by high-resolution computed tomography ...and an open lung biopsy. Anti-Golgi complex autoantibodies (AGA) and anti-Ro52 antibodies were simultaneously detected at high concentrations. Autoantibodies to aminoacyl-tRNA synthetases (ARS) were negative. The patient was treated with corticosteroids for six months. During the seven-year follow-up, NSIP had a slow progression and patient had not developed the clinical features of CTD. The present study potentially demonstrates that the autoimmune process elicited by AGA and/or Ro/SSA may play a role in promoting idiopathic NSIP independently of the typical ARS routes, which has not been reported thus far.
Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was ...performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio OR 19.55, 95%CI 5.04-75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71-8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3' UTR (OR 4.33, 95%CI 2.03-9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73-11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33-5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles.
Thromboembolism is the most common cause of death in autopsied patients. Recently, this disorder has become a topic of interest due to it being a frequent complication of COVID-19 infection. This ...book discusses pulmonary thromboembolism in COVID-19 and non-COVID-19 patients, such as those with malignancies such as paraneoplastic symptoms or heart and lung diseases.
Although international organizations as subjects of international law are
obliged to respect fundamental human rights in their acting, a very small
number of them are contracting parties to ...international instruments for human
rights protection, unlike their member states, which are contracting parties
to many of them. As international organizations take more and more activities
that can and often result in violation of human rights there is an obvious
problem to what forum victims of those violations can turn to for determining
responsibility of the international organization. The European Court of Human
Rights and the European Court of Justice have developed through their
practices modalities for indirect control of acts of international
organizations by controlling the acts of their member states, which result
from their duties as members of those organizations. The paper assumes that
such control is efficient and that it fills the void in the international
system of determining responsibility for violation of human rights through
acts of international organizations according to which, the states basically
keep on being responsible for violation of human rights.
Iako medjunarodne organizacije, kao subjekti medjunarodnog prava, imaju obavezu
da postuju osnovna ljudska prava u svom delovanju, veoma mali broj
organizacija su ugovornice medjunarodnih instrumenata za zastitu ljudskih
prava, za razliku od clanica organizacija koje su ugovornice mnogih. Kako
medjunarodne organizacije preduzimaju sve vise aktivnosti koje za posledicu
mogu imati, i cesto imaju, krsenje ljudskih prava, postaje ocigledan problem
pitanje kom forumu mogu zrtve da se obrate radi utvrdjivanja odgovornosti
medjunarodne organizacije. Evropski sud za ljudska prava i Evropski sud pravde
su kroz svoju praksu razvili mogucnost indirektne kontrole akata medjunarodnih
organizacija, preko kontrole akata clanica koji proisticu iz obaveza iz
clanstva u tim organizacijama. Rad polazi od pretpostavke da je takva
kontrola delotvorna i da popunjava prazninu u medjunarodnom sistemu
utvrdjivanja odgovornosti za krsenja ljudskih prava aktima medjunarodnih
organizacija, u kojem je odgovornost za krsenja ljudskih prava i dalje,
sustinski, odgovornost drzava.
We reported the first case of inoperative thymic adenocarcinoma successfully palliative treated by the double-stent procedure. In a patient who expressed stridor, computed tomography was done and ...necrotic mediastinal mass, which protrudes into a trachea, was demonstrated. Fiberoptic bronchoscopy showed tracheal infiltration and 70% stenosis; therefore, surgical resection was inapplicable. Recanalization with repeated argon plasma coagulation and debridement of necrotic mass was performed, followed by placement of the endotracheal stent, radiotherapy, and chemotherapy. After 1 year, the patient developed gastric aspiration and tracheoesophageal fistula; therefore, the esophageal stent was placed. The outcome was lethal, but the placement of endotracheal stent significantly increased a length of survival for the patient with invasive thymic adenocarcinoma.
Angiomatosis of the thoracic wall Stojsic, Jelena; Markovic, Jelena; Subotic, Dragan ...
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association
18, Številka:
1
Journal Article
The basis of the digital economy is electronic commerce (e-commerce), based on contracting which increasingly relies on the use of a digital technology. A contract represents the basis of legal ...obligation, as well as the foundation of the validity and legitimacy of legal rules, dating back to the theory of the social contract. The functioning of the digital society and digital economy has introduced the process of digitization into the scope of the Contract Law and contracting practice. On the example of wrap contracts, as a kind of online contracts by access (adhesion contracts), the author shows how new practices in contracting affect the traditional obligation law institutes.
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