Preoperative evaluation of cytologically indeterminate thyroid nodules with 18F-FDG PET

Esse artigo tem o objetivo de discutir o papel da tomografia por emissão de pósitrons (PET) com 18F-FDG na avaliação pré-operatória de pacientes com nódulos de tireóide com citologia indeterminada. Para o cálculo da sensibilidade, foram selecionados todos os estudos com pacientes com carcinoma de tireóide. Para o cálculo da especificidade, foram selecionados apenas estudos desenhados para avaliação dos pacientes com nódulos com citologia indeterminada. O achado de captação focal na PET-18F-FDG relacionou-se com a presença de carcinoma de tireóide na maioria dos estudos. A sensibilidade do exame foi bastante alta na detecção de malignidade tireoidiana, porém sua especificidade variou de 0% a 66%, sendo de 39% em estudo brasileiro. Concluindo, os estudos indicam que a PET-18F-FDG pode reduzir o número de tireoidectomias desnecessárias em pacientes com nódulos de tireóide com citologia indeterminada. Entretanto, o percentual relativamente elevado de resultados falso-positivos, o alto custo, a baixa disponibilidade do exame em países em desenvolvimento e a pouca experiência clínica ainda limitam o uso da PET-18F-FDG com essa finalidade.The aim of this article is to discuss the role of 18F-FDG Positron Emission Tomography (PET) in the preoperative evaluation of patients with cytologically indeterminate thyroid nodules. All studies with patients with thyroid cancer were selected to the calculation of sensitivity. Only studies aiming to evaluate patients with thyroid nodules whose cytological result was indeterminate were selected to establish the specificity. The finding of focal 18F-FDG uptake at PET was associated with the presence of thyroid malignancy in most of the studies. The sensitivity of the exam to the detection of thyroid malignancy was extremely high, but the specificity varied from 0 to 66%. In our experience, the specificity was 39%. In conclusion, the studies suggest that 18F-FDG PET can reduce the number of unnecessary thyroidectomies performed in patients with cytologically indeterminate thyroid nodules. However, the relatively high percentage of false positive results, the high costs, the low availability of this exam in developing countries and the low clinical experience still restrict the use of 18F-FDG PET when recommended with this aim

A novel mutation in the glycogen synthase 2 gene in a child with glycogen storage disease type 0

<p>Abstract</p> <p>Background</p> <p>Glycogen storage disease type 0 is an autosomal recessive disease presenting in infancy or early childhood and characterized by ketotic hypoglycemia after prolonged fasting and postprandial hyperglycemia and hyperlactatemia. Sixteen different mutations have been identified to date in the gene which encodes hepatic glycogen synthase, resulting in reduction of glycogen storage in the liver.</p> <p>Case Presentation</p> <p>Biochemical evaluation as well as direct sequencing of exons and exon-intron boundary regions of the <it>GYS2 </it>gene were performed in a patient presenting fasting hypoglycemia and postprandial hyperglycemia and her parents. The patient was found to be compound heterozygous for one previously reported nonsense mutation (c.736 C>T; R243X) and a novel frameshift mutation (966_967delGA/insC) which introduces a stop codon 21 aminoacids downstream from the site of the mutation that presumably leads to loss of 51% of the COOH-terminal part of the protein. The glycemia and lactatemia of the parents after an oral glucose tolerance test were evaluated to investigate a possible impact of the carrier status on the metabolic profile. The mother, who presented a positive family history of type 2 diabetes, was classified as glucose intolerant and the father, who did not exhibit metabolic changes after the glucose overload, had an antecedent history of hypoglycemia after moderate alcohol ingestion.</p> <p>Conclusion</p> <p>The current results expand the spectrum of known mutations in <it>GYS2 </it>and suggest that haploinsufficiency could explain metabolic abnormalities in heterozygous carriers in presence of predisposing conditions.</p

Exploring the link between MORF4L1 and risk of breast cancer.

INTRODUCTION: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. METHODS: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. RESULTS: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. CONCLUSIONS: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Effects of Biochar and Clinoptilolite on Composition and Gaseous Emissions during the Storage of Separated Liquid Fraction of Pig Slurry

The storage of animal manure is a major source of gaseous emissions. The aim of this study was to evaluate the effects of biochar and clinoptilolite on the composition and gaseous emissions during the storage of separated liquid fraction of pig slurry. The experiment was carried out using containers with 6 L of pig slurry each. The additives biochar and clinoptilolite were added alone and mixed to the pig slurry at a rate of 2.5% each, in a total of four treatments with three replicates including the control. Gaseous emissions were monitored by a photoacoustic multigas monitor, and slurry samples were collected at 0 and 85 days and their composition assessed. Results showed that the addition of biochar could modify the physicochemical properties of the slurry. The addition of biochar did not reduce the E. coli during the experiment while clinoptilolite decreased its prevalence. The addition of biochar or clinoptilolite reduced significantly the NH3 emission during the storage of slurry, but no advantages were gained with their combination. The addition of biochar significantly reduced the CO2 and CH4 emissions relative to clinoptilolite, however N2O emissions and global warming potential did not differ among the additives. We conclude that the biochar and clinoptilolite are recommended as a mitigation measure to reduce gaseous emissions and preserve the fertiliser value at slurry storage

Applicability of photodynamic antimicrobial chemotherapy as an alternative to inactivate fish pathogenic bacteria in aquaculture systems

Aquaculture activities are increasing worldwide, stimulated by the progressive reduction of natural fish stocks in the oceans. However, these activities also suffer heavy production and financial losses resulting from fish infections caused by microbial pathogens, including multidrug resistant bacteria. Therefore, strategies to control fish infections are urgently needed, in order to make aquaculture industry more sustainable. Antimicrobial photodynamic therapy (aPDT) has emerged as an alternative to treat diseases and prevent the development of antibiotic resistance by pathogenic bacteria. The aim of this work was to evaluate the applicability of aPDT to inactivate pathogenic fish bacteria. To reach this objective a cationic porphyrin Tri-Py+-Me-PF was tested against nine pathogenic bacteria isolated from a semi-intensive aquaculture system and against the cultivable bacteria of the aquaculture system. The ecological impact of aPDT in the aquatic environment was also tested on the natural bacterial community, using the overall bacterial community structure and the cultivable bacteria as indicators. Photodynamic inactivation of bacterial isolates and of cultivable bacteria was assessed counting the number of colonies. The impact of aPDT in the overall bacterial community structure of the aquaculture water was evaluated by denaturing gel gradient electrophoresis (DGGE). The results showed that, in the presence of Tri-Py+-Me-PF, the growth of bacterial isolates was inhibited, resulting in a decrease of ª7–8 log after 60–270 min of irradiation. Cultivable bacteria were also considerably affected, showing decreases up to the detection limit (ª2 log decrease on cell survival), but the inactivation rate varied significantly with the sampling period. The DGGE fingerprint analyses revealed changes in the bacterial community structure caused by the combination of aPDT and light. The results indicate that aPDT can be regarded as a new approach to control fish infections in aquaculture systems, but it is clearly more difficult to inactivate the complex natural bacterial communities of aquaculture waters than pure cultures of bacteria isolated from aquaculture systems. Considering the use of aPDT to inactivate pathogenic microbial community of aquaculture systems the monitoring of microorganisms is needed in order to select the most effective conditions.We are grateful to aquaculture staff for the help in water sampling and Carla M. B. Carvalho (University of Aveiro, Portugal) for all the help during the PS synthesis. Thanks are also due to the University of Aveiro, Fundação para a Ciência e a Tecnologia (FCT) and FEDER for funding the Organic Chemistry Research Unit (QOPNA) and to Centro de Estudos do Ambiente e do Mar (CESAM) for funding the Microbiology Research Group.publishe