Molecular testing for thyroid nodules: Where are we now?

Approximately 25% of the fine needle aspiration samples (FNAB) of thyroid nodules are classified as "indeterminate samples", that means, Bethesda III and IV categories. Until the last decade, most of these cases underwent diagnostic surgery, although only a minority (13-34%) confirmed malignancy postoperatively. In view of this, with the objective of improving the preoperative diagnosis in these cases, the molecular tests emerged, which are validated from the diagnostic point of view, presenting good performance, with good diagnostic accuracy, being able to avoid diagnostic surgeries. With the advancement of knowledge of the role of each of the mutations and gene rearrangements in thyroid oncogenesis, molecular markers have left to play only a diagnostic role and have been gaining more and more space both in defining the prognostic role of the tumor, as well as in the indication of target therapy. Thus, the objective of this review is to show how to use the tool of molecular tests, now commercially available in the world, in the management of indeterminate cytological nodules, assessing the pre-test malignancy risk of the nodule, through clinical, ultrasonographic and cytological characteristics, and decide on the benefit of molecular testing for each patient. In addition, to discuss its new and promising prognostic and therapeutic role in thyroid cancer.

Glucocorticoids as a risk factor for infection and adverse outcomes in non-HIV and non-transplant patients with cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM), an opportunistic fungal infection affecting immunocompromised hosts, leads to high mortality. The role of previous exposure to glucocorticoids as a risk factor and as an outcome modulator has been observed, but systematic studies are lacking. OBJECTIVE: The primary aim of this study is to evaluate the impact of glucocorticoid use on the clinical outcomes, specifically mortality, of non-HIV and non-transplant (NHNT) patients diagnosed with CM. METHODS: We queried a global research network to identify adult NHNT patients with CM based on ICD codes or recorded specific Cryptococcus CSF lab results with or without glucocorticoid exposure the year before diagnosis. We performed a propensity score-matched analysis to reduce the risk of confounding and analysed outcomes by glucocorticoid exposure. We used a Cox proportional hazards model for survival analysis. RESULTS: We identified 764 patients with a history of glucocorticoid exposure and 1267 patients without who developed CM within 1 year. After propensity score matching of covariates, we obtained 627 patients in each cohort. The mortality risk in 1 year was greater in patients exposed to prior glucocorticoids (OR: 1.3, CI: 1.2-2.0, p = 0.002). We found an excess of 45 deaths among CM patients with previous glucocorticoid use (7.4% increased absolute risk of dying within 1 year of diagnosis) compared to CM controls without glucocorticoid exposure. Hospitalisation, intensive care unit admission, emergency department visits, stroke and cognitive dysfunction also showed significant, unfavourable outcomes in patients with glucocorticoid-exposed CM compared to glucocorticoid-unexposed CM patients. CONCLUSIONS: Previous glucocorticoid administration in NHNT patients seems to associate with 1-year mortality after CM adjusted for possible confounders related to demographics, comorbidities and additional immunosuppressive medications. Serial CrAg screening might be appropriate for higher-risk patients on glucocorticoids after further cost-benefit analyses.

Diabetes Mellitus Type 2 as a Risk Factor and Outcome Modifier for Cryptococcosis in HIV Negative, Non-transplant Patients, a Propensity Score Match Analysis.

Cryptococcosis is an opportunistic fungal infection of worldwide distribution with significant associated morbidity and mortality. HIV, organ transplantation, malignancy, cirrhosis, sarcoidosis, and immunosuppressive medications are established risk factors for cryptococcosis. Type 2 diabetes mellitus (DM2) has been hypothesized as a risk factor and an outcome modifier for cryptococcosis. We aimed to compare outcomes among HIV-negative, non-transplant (NHNT) patients with and without DM2. We queried a global research network to identify NHNT patients (n = 3280). We performed a propensity score-matched (PSM) analysis comparing clinical outcomes among cryptococcosis patients by DM status. We also characterize adults with cryptococcosis and DM2 as the only risk factor. After PSM, NHNT patients with DM2 were more likely to develop cognitive dysfunction [9% vs. 6%, OR 1.6; 95% CI (1.1-2.3); P = 0.01] but had similar mortality, hospitalization, ICU, and stroke risk after acquiring cryptococcosis when compared to NHNT patients without DM2. Pulmonary cryptococcosis was the most common site of infection. Among 44 cryptococcosis patients with DM2 as the only identifiable risk factor for disease, the annual incidence of cryptococcosis was 0.001%, with a prevalence of 0.002%. DM2 is associated with increased cognitive dysfunction risk in NHNT patients with cryptococcosis. It is rare for DM2 to be the only identified risk factor for developing cryptococcosis. Kidney disease, hyperglycemia, and immune dysfunction can increase the risk of cryptococcosis in patients with DM2.

Efficacy of Duddingtonia flagrans (Bioverm®) on the biological control of buffalo gastrointestinal nematodes.

We evaluated the efficacy of Bioverm®, a commercial product containing Duddingtonia flagrans, on the control of buffalo (Bubalus bubalis) gastrointestinal nematodes. We randomly divided 12 buffaloes into two groups of six animals. In the treated group, each animal received a Bioverm®`s single dose of 1g (105 chlamydospores of D. flagrans) to 10 kg of live weight; in the control group, each animal received 1g of corn bran for each 10 kg of live weight as a placebo. Fecal samples were individually collected from 12, 24, 36, 48, 60 and 72 h after treatments. To examine 1) viability of chlamydospores passed through the gastrointestinal tract, 2 g of faeces and 1000 infective larvae (L3) were added to Petri dishes with 2% water-agar, and 2) to examine larval predation by D. flagrans during fecal cultures, 2000 L3 were added. In the Petri dishes, were observed significant reductions (p < 0.01) in the treated group after 48 (56.7%) and 60 h (91.5%). In the fecal cultures, significant reductions (p < 0.01) occurred in the treated group from 36 h (75%), with larval reduction up to 72 h. High larval predation rate occurred 60 h after Bioverm® administration. Bioverm® maintained viability and predation capacity after passage through the buffalo's gastrointestinal tract, showing efficacy on gastrointestinal nematodes.

Association between Duddingtonia flagrans, dimethylsulfoxide and ivermectin for the control of Rhabditis spp. in cattle.

Cattle parasitic otitis caused by the nematode Rhabditis spp. is a serious health problem in Brazil, a situation which is confounded by lack of effective control measures. In vitro studies associating biological and chemical control as an alternative method showed promising results. The objective was to evaluate the combined use of Duddingtonia flagrans (AC001), 10% dimethylsulfoxide (DMSO), and 1.9% ivermectin for the in vivo control of Rhabditis spp., in naturally infected Gyr cattle. For this purpose, 48 animals, whose infection in both ears was diagnosed, were randomly assigned to 6 groups: group 1 (ivermectin 1.9%); group 2 (10% DMSO); group 3 (AC001); group 4 (ivermectin 1.9% + 10% DMSO w/v); group 5 (1.9% ivermectin + AC001 w/v); group 6 (10% DMSO + AC001 v/v). The treatments were performed in a single dose, in the right ears, with the left ears remaining untreated, as a control group. There was a significant reduction (p < 0.01) in the number of nematodes in the treated groups in relation to the control, with the following best efficacies: groups 1 and 2, 47% and 52.9%, respectively, 7 days after treatment; groups 3, 4, and 5, 47.8%, 48.6% and 36.7%, respectively, 14 days post-treatment; group 6, 38.4%, 21 days post-treatment. It was concluded that the combination of chemical compounds and D. flagrans in a single application was effective for the in vivo control of Rhabditis spp. in naturally infected cattle.

A Novel Fusion-Based Texture Descriptor to Improve the Detection of Architectural Distortion in Digital Mammography.

Architectural distortion (AD) is the earliest sign of breast cancer that can be detected on a mammogram, and it is usually associated with malignant tumors. Breast cancer is one of the major causes of death among women, and the chance of cure can increase significantly when detected early. Computer-aided detection (CAD) systems have been used in clinical practice to assist radiologists with the task of detecting breast lesions. However, due to the complexity and subtlety of AD, its detection is still a challenge, even with the assistance of CAD. Recently, the fusion of descriptors has become a trend for improving the performance of computer vision algorithms. In this work, we evaluated some local texture descriptors and their possible combinations, considering different fusion approaches, for application in CAD systems to improve AD detection. In addition, we present a novel fusion-based texture descriptor, the Completed Mean Local Mapped Pattern (CMLMP), which is based on complementary information between three LMP operators (signal, magnitude and center) and the local differences between pixel values and the mean value of a neighborhood. We compared the performance of the proposed descriptor with two other well-known descriptors: the Completed Local Binary Pattern (CLBP) and the Completed Local Mapped Pattern (CLMP), for the task of detecting AD in 350 digital mammography clinical images. The results showed that the descriptor proposed in this work outperforms the others, for both individual and fused approaches. Moreover, the choice of the fusion operator is crucial because it results in different detection performances.

Germination capacity of the Pochonia chlamydosporia fungus after its passage through the gastrointestinal tract of domestic chickens (Gallus gallus domesticus).

This study evaluated the germination capacity of Pochonia chlamydosporia (VC4) fungus after its passage through the gastrointestinal tract of domestic chickens and its interaction with Ascaridia galli and Heterakis gallinarum eggs. Twenty-two domestic chickens were divided in two groups: control group (G1) received shredded corn substrate without VC4; and treatment group (G2) received a single dose of 29 g corn substrate containing 3.3 × 106 conidia/chlamydospores (VC4). Subsequently, chicken fecal samples were collected at intervals of 0, 6, 8, 10, 12, 18 and 24 h. Petri dishes from fecal samples of the treated group (G2) were subdivided (G2a and G2b), and then replicated in 2% agar-water medium for the microbiological test. After VC4 growth, approximately 200 eggs of A. galli (G2a) and H. gallinarum (G2b) were added to each subgroup to evaluation of ovicidal activity. There was fungal viability after passage through chicken gastrointestinal tract and egg predation of 59.9% and 43.2% for A. galli and H. gallinarum, respectively. The present work demonstrates the ability of the fungus P. chlamydosporia to survive after passing through the gastrointestinal tract of domestic chickens, an extreme environment (low pH, enzymes, microbiota and mechanical action), and still germinate after being excreted with feces.

Effect of silver nanoparticles (AgNP's) from Duddingtonia flagrans on cyathostomins larvae (subfamily: cyathostominae).

The in vitro effect of silver nanoparticles of the Duddingtonia flagrans filtrate enriched with chitin was evaluated on infective larvae of cyathostomins (L3). After biosynthesis, an assay was carried out with two experimental groups in microtubes, for a period of 24 h: G1 (AgNP's-D. flagrans (43.4 µg/mL) + 120 L3) and G2 (distilled water + 120 L3). At the end of this period, AgNP's-D. flagrans (G1) demonstrated an effect on L3 with a 43% reduction (p < 0.01) in relation to G2. Thus, the authors suggest new designs with AgNP's-D. flagrans for the control of cyathostomins.

Duddingtonia flagrans formulated in rice bran in the control of Oesophagostomum spp. intestinal parasite of swine.

Three experimental assays with Duddingtonia flagrans (isolated AC001) were carried out. The growth of the genus Duddingtonia present in formulation of rice bran, its predatory capability on Oesophagostomum spp. infective larvae (L3) in petri dishes (assay 1), its action in faecal cultures with eggs of that parasite (assay 2) and isolate's capability of predation after passing through gastrointestinal tract of swine (assay 3) was evaluated. At assay 3, feces were collected at time intervals of 12, 24, 36, 48, and 60 h after feed animals with the formulation. Assays 1 and 2 showed a statistical difference (p < 0.01) by the F test when comparing the treated group with the control group. At the both assays, was observed in the treated group a reduction percentage of 74.18% and 88.38%, respectively. In assay 3, there was a statistical difference between the treated group and the control group at all collection times (p < 0.01). Regarding the collection periods, there was no statistical difference over time in the treatment group (p > 0.05). The results demonstrate that the fungal isolate AC001 formulated in rice bran can prey on L3 of Oesophagostomum spp., in vitro and after passing through the gastrointestinal tract, without loss of viability. This isolate may be an alternative in the control of Oesophagostomum spp. in swine.

Nematophagous fungi combinations reduce free-living stages of sheep gastrointestinal nematodes in the field.

Gastrointestinal nematodes (GIN) can reduce or limit sheep production. Currently there is a clear deficiency in the action of drugs for the control of these parasites. Nematophagous fungi are natural enemies of GIN. Fungal combinations have potential for reducing GIN populations. The aim of this study was to evaluate the efficiency combinations of nematophagous fungi in sodium alginate matrix pellets for the biological control agents of gastrointestinal sheep nematode parasites in the field. The nematophagous fungi (0.2mg of fungus per kg of body weight), Arthrobotrys conoides, A. robusta, Duddingtonia flagrans, and Monacrosporium thaumasium were used. The treated groups were administered mycelium combinations in the following combinations: group 1 (D. flagrans+A. robusta); group 2 (M. thaumasium+A. conoides). The control group did not receive any fungal pellets. We used three groups with eight Santa Inês sheep each. Each animal was treated with approximately 1g of pellet per 10kg of live weight. During the experimental period, we evaluated: number of eggs per gram of feces (EPG), infective larvae (L3) per kg of dry matter, larvae recovered from coprocultures, packed cell volume, total plasma protein concentration of sheep, and environmental conditions. Group 2 EPG (M. thaumasium+A. conoides) differed from the control group in September and October. The number of L3/kg of dry matter recovered from animals of groups 1 and 2 at distances of 0-20 and 20-40cm from the fecal pats was lower than the control group. The packed cell volume and total plasma proteins of treated animals were similar to those of the control group. The combination of treatment groups (D. flagrans+A. robusta and M. thaumasium+A. conoides) reduced the number of L3/kg of pasture. Therefore, treatment of nematophagous fungal combinations have the potential to manage free-living stages of GIN in sheep.

Viability of Strongyloides venezuelensis eggs and larvae in vermiculite containing the fungus Duddingtonia flagrans.

Strongyloidiasis is the most clinically important disease among the infections caused by geohelminths, seeing that this parasite can cause autoinfection. The use of nematophagous fungi like Duddingtonia flagrans, that have predation action on eggs and infecciososas forms of helminths, emerges as an alternative method for environmental control. For this reason, analyzing the viability of larvae and eggs of Strongyloides venezuelensis and the action of Duddingtonia flagrans AC001 in vermiculite, as well as the action of the nematophagous fungi in different growth stages, is important to elaborate and define the best culture conditions that favor the activity of the fungus. Two different growth conditions were applied: both eggs and AC001 fungi were added at the same time to the vermiculite (assay A) and the addition of eggs after the growth of the AC001 fungi in the vermiculite (assay B). To recover the L3 larvae, the Baermann-Moraes method was applied, followed by the counting of L3 dead and alive. At last, it was observed that the vermiculite enriched with organic material is an adequate culture medium not only for the growth of the S. venezuelensis but also for the growth of the D. flagrans fungus, being therefore, a satisfactory culture medium for tests of viability and predatory action of this fungus. It was also observed that the activity of the AC001 fungus is greater when it is growing concomitantly with the eggs, in other words, when it is in the adaptation phase.

Talking to the dead: using Post-mortem data in the assessment of stress in tiger sharks (Galeocerdo cuvier) (Péron and Lesueur, 1822).

Sharks are very sensitive to stress and prone to a high mortality rate after capture. Since approximately 50 million of sharks are caught as bycatch every year, and current recommendations to reduce the impact of commercial fishing strongly support immediate release, it is imperative to better understand post-release mortality caused by the stress of capture and handling. Blood samples allow the assessment of stress levels which are valuable tools to reduce mortality in commercial, recreational and scientific fishing, being essential for the improvement in those conservation measures. Biochemical analyses are widely used for sharks as stress indicators, with secondary plasma parameters (lactate, glucose and ions) being the most often employed assays. However, it is virtually impossible to determine baseline plasma parameters in free-ranging sharks, since blood withdrawal involves animal capture and restrain, which are stressful procedures. This study aims at analyzing secondary parameters of five healthy tiger sharks captured with circular hooks and handlines in Fernando de Noronha (Northeastern Brazil) and comparing them with secondary parameters of three dead tiger sharks caught off Recife (also Northeastern Brazil). The results showed that the analysis of some plasma constituents in dead animals may be an efficient tool to assess stress and lethality. However, traditional parameters such as glucose and calcium, need to be used with caution. The results also demonstrated the extreme importance of urea and phosphorus for assessing stress response and mortality in tiger sharks, both parameters frequently neglected and of utmost importance for shark's homeostasis.

Assessing the Microbial Quality of Shrimp (Xiphonaeus kroyeri) and Mussels (Perna perna) Illegally Sold in the Vitória Region, Brazil, and Investigating the Antimicrobial Resistance of Escherichia coli Isolates.

The consumption of seafood is crucial for food security, but poor hygiene along the food production chain can result in low microbiological quality, posing significant risks for public health and seafood quality. Thus, this study aimed to assess the microbiological quality and antimicrobial sensitivity of E. coli from 69 samples of illegally marketed shrimp and mussels in the Vitória Region, Brazil. These foods exhibited poor microbiological quality due to high counts of mesophilic, psychrotrophic, and enterobacteria microorganisms. While this issue is widespread in this area, shrimp samples displayed higher microbial counts compared to mussels, and fresh mussels had elevated counts of enterobacteria compared to frozen ones. Among the 10 E. coli isolates, none carried the genes blaCTX-M-1, blaCTX-M-2, blaCTX-M-3, blaCTX-M-15, mcr-1, mcr-2, mcr-3, mcr-4, and tet, associated with antibiotic resistance. Phenotypical resistance to tetracycline and fosfomycin was not observed in any isolate, while only 20% demonstrated resistance to ciprofloxacin. Regarding ampicillin and amoxicillin with clavulanic acid, 60% of isolates were resistant, 10% showed intermediate susceptibility, and 30% were sensitive. One isolate was considered simultaneously resistant to ß-lactams and quinolones, and none were conserved as ESBL producers. These findings highlight the inherent risks to local public health that arise from consuming improperly prepared seafood in this area.

Clinical Characteristics and Outcomes of Chagas Disease in the United States: A Multicenter Retrospective Analysis.

Chagas disease affects approximately 300,000 patients in the United States. We evaluated a multicenter U.S.-based network to obtain clinical characteristics and outcomes of chronic Chagas disease by disease forms. This was a U.S.-based, multicenter, population-based, retrospective cohort study. We queried TriNetX, a global research network, to identify patients with dual-positive IgG serology for Trypanosoma cruzi. We captured outcomes of interest for up to 5 years. We found 429 patients with evidence of dual-positive T. cruzi IgG out of 19,831 patients with an available test result from 31 U.S. medical centers. The positive proportion for those tested was 2.2%, up to 4.6% among Hispanics. We found a prevalence of a positive Chagas serology of 0.02% among Hispanics. Cardiomyopathy risk reached an annual rate of 1.3% during the initial 5 years of follow-up among patients with the indeterminate form. We found no new events for pulmonary embolism, sudden death, or left ventricular aneurysms at 5 years. Annual risks for arrhythmias and stroke for chronic Chagas cardiomyopathy (CCC) were 1.6% and 0.8%, respectively. The yearly mortality and hospitalization rates for CCC were 2.7% and 17.1%, respectively. Only 13 patients had a documented antitrypanosomal therapy course within 6 months after diagnosis. Of those receiving treatment, 10 patients received benznidazole and three nifurtimox. Chagas disease screening in patients from endemic areas living in the United States remains crucial. Chronic Chagas cardiomyopathy carries a considerable disease burden, translating into increased morbidity and mortality and an enlarging medical health service utilization.

Treatment strategies for low-risk papillary thyroid carcinoma: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM).

Increasingly sensitive diagnostic methods, better understanding of molecular pathophysiology, and well-conducted prospective studies have changed the current approach to patients with thyroid cancer, requiring the implementation of individualized management. Most patients with papillary thyroid carcinoma (PTC) are currently considered to have a low risk of mortality and disease persistence/recurrence. Consequently, current treatment recommendations for these patients include less invasive or intensive therapies. We used the most recent evidence to prepare a position statement providing guidance for decisions regarding the management of patients with low-risk PTC (LRPTC). This document summarizes the criteria defining LRPTC (including considerations regarding changes in the TNM staging system), indications and contraindications for active surveillance, and recommendations for follow-up and surgery. Active surveillance may be an appropriate initial choice in selected patients, and the criteria to recommend this approach are detailed. A section is dedicated to the current evidence regarding lobectomy versus total thyroidectomy and the potential pitfalls of each approach, considering the challenges during long-term follow-up. Indications for radioiodine (RAI) therapy are also addressed, along with the benefits and risks associated with this treatment, patient preparation, and dosage. Finally, this statement presents the best follow-up strategies for LRPTC after lobectomy and total thyroidectomy with or without RAI.

Analysis of the status of treatment of benign thyroid diseases - a public health problem aggravated in the COVID-19 pandemic era.

OBJECTIVE: Goiters and benign nodules detected in the thyroid are growing lesions and the COVID-19 pandemic have negatively impacted on their surgical treatment. The appropriate selection of patients to treatment will improve the overall health status. This article review will focus on the impact of the COVID-19 pandemic on treatment of benign conditions of the thyroid gland and their implications. METHODS: This review pointed out the status of the health system in developing country and the problems to treat benign surgical diseases of thyroid. Aspects of epidemiology, incidence, clinical presentation and surgical treatment of goiters, economic and health status impact were cited. RESULTS: All surgical treatment of goiter and other benign conditions were postponed, forced to redirect, and reschedule all benign surgeries, situation aggravated by poor public management and closure of hospital beds. These conditions have caused deterioration in patients' physical (decompensated thyroid disease) and mental health status, increasing work disabilities and burdening society by increasing the social and health cost. The overall situation could be catastrophic in emergent countries where this increased disease-related social expenditure on surgical treatment may increase the risk of national impoverishment as increase the treatment cost. Brazilian Society Head and Neck Surgery related some recommendations and new suggestions were made to safely treat these high potential hazard surgical conditions. CONCLUSIONS: Surgeries for goiter and benign thyroid conditions can be performed during the COVID-19 pandemic, following strict safety protocols for the patient and the medical team, reducing the negative economic and on patient health impact.

Feasibility of a snowball sampling survey to study active surveillance for thyroid microcarcinoma treatment among endocrinologists and surgeons of Brazil.

OBJECTIVES: This study aims to investigate if a sampling method using virtual networks is feasible to survey AS adoption among this "hard-to-reach" population of Brazilian doctors. METHODS: An online piloted 11-point structured survey questionnaire (designed using Googleforms®) probed the actual treatment patterns for adult patients with PTMCs, including treatment decision-making nonoperative options, was undertaken between 10 November and 30 November 2020. Participants were reached by the mobile phone Application (APP) and a snowball sampling strategy was used to recruit a total of 4783 members (maximum number of potential reach), which is the total of doctors of the all 21 social media WhatsApp® groups. RESULTS: From a total of 4783 members (maximum number of potential reach), there were 657 (13.7%) doctors (actual reach) who clicked the web link of the questionnaire, out of whom 512 (10.7%) fully completed the online survey. Among the survey respondents, 361 were endocrinologists (70.5%) and 151 were surgeons (29.5%). Overall, for low-risk PTMCs in an elderly patient, 118 responders (23%) recommend AS, while 390 (76%) recommend immediate surgery as the management, including lobectomy (18.5%) and Total Thyroidectomy (58.2%). The present responders tended to recommend surgery for PTMCs that were located adjacent to the dorsal surface of the thyroid, were multiple, or raised the size during the follow-up. CONCLUSION: Using snowball sampling strategy as an innovative route to conduct surveys was feasible and applicable but the rate of response was still very low. Our data also suggests the need to investigate if AS is embraced by Brazilian doctors.

Intermediate-risk thyroid carcinoma: indicators of a poor prognosis.

OBJECTIVE: The intermediate-risk (IR) category includes tumors with different degrees of aggression. We aimed to identify the risk factors associated with unfavorable response to initial treatment and compare the effect of low/high radioactive iodine (RAI) therapy. METHODS: A total of 614 IR patients were selected from a database, during 1972-2015. All patients underwent total thyroidectomy and RAI therapy and were reclassified after 12-18 months into the favorable (complete/indeterminate) response group and the unfavorable (biochemical/incomplete structural) response group. A total of 92 patients were assessed for late response (mean: 9.19 ± 5.73 years). Age, gender, tumor size, histology, multifocality, vascular invasion, extrathyroidal extension, presence and number of lymph node metastasis, and stimulated thyroglobulin at ablation (sTg) were evaluated. RESULTS: Mean age at diagnosis was 41.47 ± 15.81 years, and 83.6% of the patients were female. Within 12-18 months after initial therapy, unfavorable response was detected in 41.2% of the patients and was associated, in multivariate analysis, with lymph node metastasis (p = 0.041; odds ratio [OR] = 1.9), presence of more than five metastatic lymph nodes (p = 0,017; OR = 2.6), and sTg > 10 ng/mL (p = 0.005; OR = 10.0). For patients with a longer follow-up, sTg >10 ng/mL was associated with unfavorable response (p = 0.002; OR = 6.8). A higher RAI dose was not related to better prognosis at the end of the follow-up. CONCLUSION: A sTg level of >10 ng/mL and lymph node metastasis were associated with an unfavorable response 12-18 months after initial treatment. A RAI dose below 150 mCi was proven sufficient to treat IR patients.

Prognostic factors for incomplete response in thyroid microcarcinoma: an analysis of initial response to therapy in 517 patients.

OBJECTIVE: Although thyroid microcarcinoma (TMC) usually has a favorable prognosis, some patients present a higher risk of disease recurrence or persistence. Thus, we aimed at identifying possible risk factors associated with an incomplete response to therapy in TMC. METHODS: This was a retrospective study of 517 patients with TMC treated with total thyroidectomy, with or without radioactive iodine (RAI) therapy, reclassified after 1.1 ± 0.4 years according to the response to treatment into "favourable" (excellent/indeterminate) or "unfavorable" (biochemical/structural incomplete) responses. We evaluated participants' age, sex, tumor size, histological variants, multifocality, presence of vascular/lymphatic/perineural invasion, extrathyroidal extension, metastatic lymph nodes (LN), and distant metastasis. The effect of RAI therapy on the response range was analyzed in a given subgroup. RESULTS: The mean age observed was 46.4 ± 12.0 years, and 89.7% were female. We noted 97.5% with papillary carcinoma, 27.8% with multifocality and 11.2% with LN metastasis. Although the majority of patients had a low risk of recurrence/persistence (78%), 75% were submitted to RAI therapy. Incomplete response (20.7%) was associated with multifocality (p=0.041; OR=1.619) and metastatic LN (p=0.041; OR=1.868). These variables were strongly correlated (p=0.000; OR=3.283). No cut-off of tumor size was identified as a predictor of incomplete response by the receiver operating curve analysis. RAI treatment did not influence the response of patients with multifocality or LN metastasis. CONCLUSION: Multifocality and LN metastasis are independent risk factors for incomplete response in TMC patients and are strongly correlated. Additional RAI therapy was not associated with a more favorable response in these subgroups.

Efficiency of the Bioverm ® (Duddingtonia flagrans) fungal formulation to control in vivo and in vitro of Haemonchus contortus and Strongyloides papillosus in sheep.

The objective of the present work was to evaluate the efficiency of Bioverm® fungal formulation (Duddingtonia flagrans-AC001) in controlling Haemonchus contortus and Strongyloides papillosus in sheep. In vitro predation tests were carried out in Petri dishes containing agar culture medium 2%. Four experimental groups were formed, with five replicates each: Group 1: 1 g of Bioverm ® and 1000 third-stage larvae (L3) of H. contortus; Group 2: 1000 L3 of H. contortus; Group 3: 1 g of Bioverm ® and 1000 L3 of S. papillosus; and Group 4: 1000 L3 of S. papillosus. In the in vivo tests, twelve 11-month-old sheep males positive for H. contortus were used. The animals were sorted in two groups (treatment and control), based on fecal egg counts (eggs per gram, EPG). Each group comprised six animals: treatment group-each animal received orally 100 g of Bioverm ® ; and control group-each animal received orally 100 g of rice. Subsequently, feces from these animals were collected at 12, 24, 36, 48, 60, 72, 84, and 96 h after Bioverm ® administration. In vitro results demonstrate that D. flagrans kept its predatory activity with 91.5% of mean reduction percentage of L3. After the passage test, Bioverm ® presented efficacy already after 12 h of its administration and kept similar results for 60 h. Bioverm® fungal formulation (D. flagrans-AC001) was efficient in reducing the population of H. contortus and S. papillosus under laboratory conditions in sheep feces. However, further studies are needed under natural conditions of ruminant grazing to prove the efficiency of this product.