Background: Radiotherapy increases the risk of thyroid cancer (TC); patients submitted to this treatment should undergo a long-term follow-up. Our aim is to describe the features and outcomes of ...young patients who developed TC after radiotherapy. Methods: At our center, patients undergoing radiotherapy directly or indirectly involving the thyroid are regularly followed up in order to detect early dysfunction or nodules. Herein, we report the cases of 10 patients who were submitted to radiotherapy and developed TC. Clinical Findings: Seven patients were irradiated in the neck and 3 in nearby regions. The mean age at the last radiotherapy session was 10 ± 5.5 years. The average time until the appearance of the first thyroid nodule was 14 ± 4.7 years. The mean size increment of the nodules was 2.4 ± 1.6 mm/year. On the first cytology, only 2 results were suspicious of papillary thyroid cancer (PTC). All patients presented a histology of PTC. Eight were in stage I and 2 in stage II. The median follow-up from primary diagnosis to TC and beyond was 20 and 3 years, respectively. Conclusions: In these patients, cytologies may be difficult to interpret due to persistent benign results. The threshold for surgical indication may be anticipated, considering the increased risk of TC. We report the evolution of these nodules over time, from the end of primary oncological treatment.
Systemic autoinflammatory diseases (SAIDs) are a group of disorders that constitute a rare cause of recurrent fevers. Recurrent fevers are defined as periodic febrile episodes lasting from days to ...weeks, separated by symptom-free intervals of variable duration. They present multiple etiologies, representing a diagnostic challenge. Mevalonate kinase deficiency (MKD) is a genetic SAID, a rare hereditary recurrent fever syndrome (HRF) caused by pathogenic variants in the mevalonate kinase (MVK) gene. It is characterized by the early onset of periodic fever flares, frequently associated with joint, gastrointestinal, skin, and lymph node involvement. Although elevated serum immunoglobulin D (IgD) levels were previously considered an MKD's hallmark, normal values do not exclude it. High serum immunoglobulin A (IgA) is frequent. An acute-phase response and elevated urinary mevalonic acid (UAV) excretion during flares may aid in the diagnosis. Genetic testing is an essential tool to confirm the diagnosis. The authors report two siblings presenting with early infancy onset of recurrent febrile illness and characteristic associated symptoms, one of which was initially misdiagnosed with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome. MKD diagnoses were only established at 12 and nine years old, respectively, after the identification of the same two MVKgene variants. The diagnosis in the eldest favored the earlier recognition of MKD in the youngest. Owing to its wide spectrum of manifestations, with many being nonspecific and/or shared with other more frequent entities, a significant proportion of MKD patients present a long delay until its final establishment. These cases illustrate the MKD diagnosis and management's difficulties, reinforcing the importance of a careful clinical history and HRF awareness for its prompt diagnosis and appropriate precocious referral.
Gastric cancer is one of the most incident and deadliest malignancies in the world. Gastric cancer is a heterogeneous disease and the end point of a long and multistep process, which results from the ...stepwise accumulation of numerous (epi)genetic alterations, leading to dysregulation of oncogenic and tumor suppressor pathways. Gastric cancer stem cells have emerged as fundamental players in cancer development and as contributors to gastric cancer heterogeneity. For this special issue, we will report last year's update on the gastric cancer molecular classification, and in particular address the gastric cancer groups who could benefit from immune checkpoint therapy. We will also review the latest advances on gastric cancer stem cells, their properties as gastric cancer markers and therapeutic targets, and associated signaling pathways. The understanding of the molecular basis underlying gastric cancer heterogeneity and of the role played by gastric cancer stem cells in cancer development and heterogeneity is of major significance, not only for identifying novel targets for cancer prevention and treatment, but also for clinical management and patient stratification for targeted therapies.
On a world scale, group A human rotaviruses are the most common cause of severe acute gastroenteritis during infancy and childhood, including five (G1, G2, G3, G4, and G9) epidemiologically important ...genotypes. Among these, G2 denotes a different genogroup which appears to have a cyclic pattern of occurrence and yet little information is available about its genetic variability. The aim of this report was to characterize the emergence of G2 genotype in Paraupebas, Southern Pará State, Brazil, some of which detected after introduction of rotavirus vaccine. A total of 241 fecal specimens from young children with acute gastroenteritis were collected from the "Yutaka Takeda Hospital," a Municipality Hospital, and at the Parauapebas' Health Unit, Pará, from January to September 2006 and during March to November 2008. All samples were tested for rotavirus using immunochromatography, polyacrylamide gel electrophoresis (PAGE), and RT-PCR, yielding an overall positivity of 12.45% (30/241). Rotavirus G2P4 was identified in 27 of 30 samples (90%), followed by G1P8 (2/30, 6.67%) and G9P8 (1/30, 3.33%). Phylogenetic analysis was performed in 15 of the G2 strains, all of which grouped into lineage II. Four of these strains clustered into sublineage II-a (year 2006) and 11 into one possible new sublineage named II-c (year 2008, except SAL-1920-C). The recent re-emergence of G2 genotype associated with lineage II in Brazil warrants the continuous monitoring of circulating rotavirus strains following the nationwide universal use of rotavirus vaccine. J. Med. Virol. 82:712-719, 2010.
Human norovirus is the first cause of foodborne disease worldwide, leading to extensive outbreaks of acute gastroenteritis, and causing around 200,000 children to die annually in developing ...countries. No specific vaccines or antiviral agents are currently available, with therapeutic options limited to supportive care to prevent dehydration. The infection can become severe and lead to life-threatening complications in young children, the elderly and immunocompromised individuals, leading to a clear need for antiviral agents, to be used as treatments and as prophylactic measures in case of outbreaks. Due to the key role played by the viral RNA-dependent RNA polymerase (RdRp) in the virus life cycle, this enzyme is a promising target for antiviral drug discovery. In previous studies, following in silico investigations, we identified different small-molecule inhibitors of this enzyme. In this study, we rationally modified five identified scaffolds, to further explore structure-activity relationships, and to enhance binding to the RdRp. The newly designed compounds were synthesized according to multiple-step synthetic routes and evaluated for their inhibition of the enzyme in vitro. New inhibitors with low micromolar inhibitory activity of the RdRp were identified, which provide a promising basis for further hit-to-lead optimization.
This study focused the ecotoxicological evaluation of four different pesticides (chlorpyrifos, glyphosate, vinclozolin, endosulfan), sprayed into an agricultural soil, using a standard battery of ...aquatic bioassays for testing of soil elutriates: Vibrio fischeri -Microtox®; Pseudokirchneriella subcapitata growth inhibition; Daphnia magna acute and chronic toxicity. Despite relevant pesticide residues were recovered from the soil matrix (concentrations higher than 1000μgkg−1), much lower concentrations could be retrieved from elutriates (highest records for endosulfan of ca. 250ngL−1and 1400ngL−1; dissolved and particulate concentration, respectively) and little effects were generally found in the bioassays. Lethal effects (D. magna 48h-EC50 of 36.8%) could be noticed following exposure to the endosulfan elutriate. Elutriates induced no toxicity on V. fischeri; algal growth was generally inhibited at high elutriate dilutions and stimulated at the lower elutriate dilutions; and no overall impairment of D. magna life-history was noticed. Results revealed that cross-contamination during field application, input of organic matter and nutrients by elutriates in test solutions, and choice of test species and endpoints may constrain the ecotoxicological assessment. Suitability of established aquatic bioassay test batteries for these purposes, and questioning on whether direct assays with soil organisms could be more protective tools is discussed.
Adipsia in a Diabetes Insipidus Patient Pereira, Maria Conceição; Vieira, Margarida M.; Pereira, Joana Simões ...
Case reports in oncology,
09/2015, Letnik:
8, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Central diabetes insipidus is a very common disorder after brain surgery or/trauma or even in the presence of brain inflammatory diseases. Polyuria and polydipsia are the clinical markers, but ...sometimes clinical situations are presenting with no thirst. These are not frequent but are life-treating conditions. Diagnosis is not easy, and for this reason some cases are treated late. We describe here a very infrequent oncological case of dangerous adipsic diabetes insipidus in a young girl who survived.
Two-thirds of small-bowel transplantation (SBT) recipients develop bacteremia, with the majority of infections occurring within 3 months post-transplant. Sepsis-related mortality occurs in 31% of ...patients and is commonly caused by bacteria of gut origin, which are thought to translocate across the implanted organ. Serial post-transplant surveillance endoscopies provide an opportunity to study whether the composition of the ileal and colonic microbiota can predict the emergence as well as the pathogen of subsequent clinical infections in the SBT patient population. Five participants serially underwent aspiration of ileal and colonic bowel effluents at transplantation and during follow-up endoscopy either until death or for up to 3 months post-SBT. We performed whole-metagenome sequencing (WMS) of 40 bowel effluent samples and compared the results with clinical infection episodes. Microbiome composition was concordant between participants and timepoint-matched ileal and colonic samples. Four out of five (4/5) participants had clinically significant infections thought to be of gut origin. Bacterial translocation from the gut was observed in 3/5 patients with bacterial infectious etiologies. In all three cases, the pathogens had demonstrably colonized the gut between 1-10 days prior to invasive clinical infection. Recipients with better outcomes received donor grafts with higher alpha diversity. There was an increase in the number of antimicrobial resistance genes associated with longer hospital stay for all participants. This metagenomic study provides preliminary evidence to support the pathogen translocation hypothesis of gut-origin sepsis in the SBT cohort. Ileal and colonic microbiome compositions were concordant; therefore, fecal metagenomic analysis could be a useful surveillance tool for impeding infection with specific gut-residing pathogens.
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