Development of multiple AI pipelines that predict neoadjuvant chemotherapy response of breast cancer using H&E-stained tissues.

In recent years, the treatment of breast cancer has advanced dramatically and neoadjuvant chemotherapy (NAC) has become a common treatment method, especially for locally advanced breast cancer. However, other than the subtype of breast cancer, no clear factor indicating sensitivity to NAC has been identified. In this study, we attempted to use artificial intelligence (AI) to predict the effect of preoperative chemotherapy from hematoxylin and eosin images of pathological tissue obtained from needle biopsies prior to chemotherapy. Application of AI to pathological images typically uses a single machine-learning model such as support vector machines (SVMs) or deep convolutional neural networks (CNNs). However, cancer tissues are extremely diverse and learning with a realistic number of cases limits the prediction accuracy of a single model. In this study, we propose a novel pipeline system that uses three independent models each focusing on different characteristics of cancer atypia. Our system uses a CNN model to learn structural atypia from image patches and SVM and random forest models to learn nuclear atypia from fine-grained nuclear features extracted by image analysis methods. It was able to predict the NAC response with 95.15% accuracy on a test set of 103 unseen cases. We believe that this AI pipeline system will contribute to the adoption of personalized medicine in NAC therapy for breast cancer.

Approach to adult patients with primary hypothyroidism in some special situations: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM)

ABSTRACT Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a search on the databases MEDLINE/PubMed, LILACS, and SciELO and selecting articles with the best evidence quality addressing the selected situations. The statement presents information about the current approach to patients in these special situations.

Approach to adult patients with primary hypothyroidism in some special situations: a position statement from the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM).

Primary hypothyroidism is a common disorder in clinical practice. The management of most cases of hypothyroidism is usually straightforward, but the best approach in some special situations may raise questions among physicians. This position statement was prepared by experts from the Brazilian Society of Endocrinology and Metabolism to guide the management of three special situations, namely, hypothyroidism in the elderly, subclinical hypothyroidism in patients with heart disease, and difficult-to-control hypothyroidism. The authors prepared the present statement after conducting a search on the databases MEDLINE/PubMed, LILACS, and SciELO and selecting articles with the best evidence quality addressing the selected situations. The statement presents information about the current approach to patients in these special situations.

Prediction of non-muscle invasive bladder cancer recurrence using machine learning of quantitative nuclear features.

Non-muscle invasive bladder cancer (NMIBC) generally has a good prognosis; however, recurrence after transurethral resection (TUR), the standard primary treatment, is a major problem. Clinical management after TUR has been based on risk classification using clinicopathological factors, but these classifications are not complete. In this study, we attempted to predict early recurrence of NMIBC based on machine learning of quantitative morphological features. In general, structural, cellular, and nuclear atypia are evaluated to determine cancer atypia. However, since it is difficult to accurately quantify structural atypia from TUR specimens, in this study, we used only nuclear atypia and analyzed it using feature extraction followed by classification using Support Vector Machine and Random Forest machine learning algorithms. For the analysis, 125 patients diagnosed with NMIBC were used; data from 95 patients were randomly selected for the training set, and data from 30 patients were randomly selected for the test set. The results showed that the support vector machine-based model predicted recurrence within 2 years after TUR with a probability of 90% and the random forest-based model with probability of 86.7%. In the future, the system can be used to objectively predict NMIBC recurrence after TUR.

Choosing Wisely for Thyroid Conditions: Recommendations of the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism

ABSTRACT Objective: Choosing Wisely (CW) is an initiative that aims to advance the dialogue between physicians and patients about low-value health interventions. Given that thyroid conditions are frequent in clinical practice, we aimed to develop an evidence-based list of thyroid CW recommendations. Materials and methods: The Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) named a Task Force to conduct the initiative. The Task Force work was based on an electronic Delphi approach. The 10 recommendations that received the highest scores by the Task Force were submitted for voting by all SBEM associates. The 5 recommendations that received the highest scores by SBEM associates are presented herein. Results: The Task Force was composed of 14 thyroidologists from 10 tertiary-care, teaching-based Brazilian institutions. The brainstorming/ideation phase resulted in 69 recommendations. After the removal of duplicates and recommendations that did not adhere to the initiative's scope, 35 remained. Then the Task Force voted to attribute a grade (0 [lowest agreement] to 10 [highest agreement]) for each recommendation. The 10 recommendations that received the highest scores by the Task Force were submitted to all SBEM associates. A total of 683 associates voted electronically, attributing a grade (0 to 10) for each recommendation. The 5 recommendations that received the highest scores by the SBEM associates compose our final list. Conclusion: A set of recommendations to avoid unnecessary medical tests, treatments, or procedures for thyroid conditions are offered with a transparent methodology. This initiative aims to foster productive interactions between physicians and patients, stimulating shared decision-making.

Choosing Wisely for Thyroid Conditions: Recommendations of the Thyroid Department of the Brazilian Society of Endocrinology and Metabolism.

OBJECTIVE: Choosing Wisely (CW) is an initiative that aims to advance the dialogue between physicians and patients about low-value health interventions. Given that thyroid conditions are frequent in clinical practice, we aimed to develop an evidence-based list of thyroid CW recommendations. METHODS: The Thyroid Department of the Brazilian Society of Endocrinology and Metabolism (SBEM) named a Task Force to conduct the initiative. The Task Force work was based on an electronic Delphi approach. The 10 recommendations that received the highest scores by the Task Force were submitted for voting by all SBEM associates. The 5 recommendations that received the highest scores by SBEM associates are presented herein. RESULTS: The Task Force was composed of 14 thyroidologists from 10 tertiary-care, teaching-based Brazilian institutions. The brainstorming/ideation phase resulted in 69 recommendations. After the removal of duplicates and recommendations that did not adhere to the initiative's scope, 35 remained. Then the Task Force voted to attribute a grade (0 [lowest agreement] to 10 [highest agreement]) for each recommendation. The 10 recommendations that received the highest scores by the Task Force were submitted to all SBEM associates. A total of 683 associates voted electronically, attributing a grade (0 to 10) for each recommendation. The 5 recommendations that received the highest scores by the SBEM associates compose our final list. CONCLUSION: A set of recommendations to avoid unnecessary medical tests, treatments, or procedures for thyroid conditions are offered with a transparent methodology. This initiative aims to foster productive interactions between physicians and patients, stimulating shared decision-making.

Is there a place for measuring serum calcitonin prior to thyroidectomy in patients with a non-diagnostic thyroid nodule biopsy?

ABSTRACT Objective: To verify the cytopathological Bethesda System classification of thyroid nodule fine-needle aspiration biopsy (FNAB) in MTC patients and to assess the role of preoperative serum calcitonin (CT) levels in the investigation of this neoplasm in medullary thyroid cancer (MTC) patients under observation at the Uopeccan (União Oeste Paranaense de Estudos e Combate ao Câncer). Materials and methods: This is a cross-sectional review of medical records of patients monitored at the thyroid cancer outpatient clinic of Uopeccan. Clinical and demographic data, laboratory tests, ultrasound images, and cytopathological findings of MTC patients were evaluated. Results and discussion: Among the 360 patients with thyroid cancer monitored in the outpatient clinic, 5.2% (n: 19/360) had MTC. The hereditary form was more prevalent (63.2%), and there was no sex preference. The most common ultrasound findings were hypoechogenicity, solid appearance and microcalcifications. The FNAB diagnoses showed a sensitivity of 47.1%, and the most common cytopathological report was Bethesda category III. Serum CT levels showed good sensitivity (84.6%) for the diagnosis of MTC, and sensitivity levels were directly associated with the size of the nodule and distant metastases. Conclusion: Bethesda category III was more prevalent in this group of MTC patients. Serum CT levels were more sensitive than cytopathology for diagnosis of this neoplasm and were able to identify all patients who could not be diagnosed by FNAB.

Is there a place for measuring serum calcitonin prior to thyroidectomy in patients with a non-diagnostic thyroid nodule biopsy?

OBJECTIVE: To verify the cytopathological Bethesda System classification of thyroid nodule fine-needle aspiration biopsy (FNAB) in MTC patients and to assess the role of preoperative serum calcitonin (CT) levels in the investigation of this neoplasm in medullary thyroid cancer (MTC) patients under observation at the Uopeccan (União Oeste Paranaense de Estudos e Combate ao Câncer). METHODS: This is a cross-sectional review of medical records of patients monitored at the thyroid cancer outpatient clinic of Uopeccan. Clinical and demographic data, laboratory tests, ultrasound images, and cytopathological findings of MTC patients were evaluated. RESULTS: Among the 360 patients with thyroid cancer monitored in the outpatient clinic, 5.2% (n: 19/360) had MTC. The hereditary form was more prevalent (63.2%), and there was no sex preference. The most common ultrasound findings were hypoechogenicity, solid appearance and microcalcifications. The FNAB diagnoses showed a sensitivity of 47.1%, and the most common cytopathological report was Bethesda category III. Serum CT levels showed good sensitivity (84.6%) for the diagnosis of MTC, and sensitivity levels were directly associated with the size of the nodule and distant metastases. CONCLUSION: Bethesda category III was more prevalent in this group of MTC patients. Serum CT levels were more sensitive than cytopathology for diagnosis of this neoplasm and were able to identify all patients who could not be diagnosed by FNAB.

Prediction of early recurrence of hepatocellular carcinoma after resection using digital pathology images assessed by machine learning.

Hepatocellular carcinoma (HCC) is a representative primary liver cancer caused by long-term and repetitive liver injury. Surgical resection is generally selected as the radical cure treatment. Because the early recurrence of HCC after resection is associated with low overall survival, the prediction of recurrence after resection is clinically important. However, the pathological characteristics of the early recurrence of HCC have not yet been elucidated. We attempted to predict the early recurrence of HCC after resection based on digital pathologic images of hematoxylin and eosin-stained specimens and machine learning applying a support vector machine (SVM). The 158 HCC patients meeting the Milan criteria who underwent surgical resection were included in this study. The patients were categorized into three groups: Group I, patients with HCC recurrence within 1 year after resection (16 for training and 23 for test); Group II, patients with HCC recurrence between 1 and 2 years after resection (22 and 28); and Group III, patients with no HCC recurrence within 4 years after resection (31 and 38). The SVM-based prediction method separated the three groups with 89.9% (80/89) accuracy. Prediction of Groups I was consistent for all cases, while Group II was predicted to be Group III in one case, and Group III was predicted to be Group II in 8 cases. The use of digital pathology and machine learning could be used for highly accurate prediction of HCC recurrence after surgical resection, especially that for early recurrence. Currently, in most cases after HCC resection, regular blood tests and diagnostic imaging are used for follow-up observation; however, the use of digital pathology coupled with machine learning offers potential as a method for objective postoprative follow-up observation.

Type IV secretion of Helicobacter pylori CagA into oral epithelial cells is prevented by the absence of CEACAM receptor expression.

BACKGROUND: Helicobacter pylori typically colonizes the human stomach, but it can occasionally be detected in the oral cavity of infected persons. Clinical outcome as a result of gastric colonization depends on presence of the pathogenicity island cagPAI that encodes a type-IV secretion system (T4SS) for translocation of the effector protein CagA and ADP-heptose. Upon injection into target cells, CagA is phosphorylated, which can be demonstrated by in vitro infection of the gastric epithelial cell line AGS, resulting in cell elongation. Here we investigated whether H. pylori can exert these responses during interaction with cells from the oral epithelium. To this purpose, three oral epithelial cell lines, HN, CAL-27 and BHY, were infected with various virulent wild-type H. pylori strains, and CagA delivery and ADP-heptose-mediated pro-inflammatory responses were monitored. RESULTS: All three oral cell lines were resistant to elongation upon infection, despite similar bacterial binding capabilities. Moreover, T4SS-dependent CagA injection was absent. Resistance to CagA delivery was shown to be due to absence of CEACAM expression in these cell lines, while these surface molecules have recently been recognized as H. pylori T4SS receptors. Lack of CEACAM expression in HN, CAL-27 and BHY cells was overcome by genetic introduction of either CEACAM1, CEACAM5, or CEACAM6, which in each of the cell lines was proven sufficient to facilitate CagA delivery and phosphorylation upon H. pylori infection to levels similar to those observed with the gastric AGS cells. Pro-inflammatory responses, as measured by interleukin-8 ELISA, were induced to high levels in each cell line and CEACAM-independent. CONCLUSIONS: These results show that lack of CEACAM receptors on the surface of the oral epithelial cells was responsible for resistance to H. pylori CagA-dependent pathogenic activities, and confirms the important role for the T4SS-dependent interaction of these receptors with H. pylori in the gastric epithelium.

Thyroid function before and after Roux-en-Y gastric bypass: an observational study.

BACKGROUND: Population studies have shown a positive association between thyroid-stimulating hormone (TSH) and body mass index. Recent studies have shown a significant increase in the prevalence of subclinical hypothyroidism (SCH) in obesity. Weight reduction after Roux-en-Y gastric bypass (RYGB) seems to significantly decrease TSH levels. OBJECTIVES: The purpose of this study was to evaluate the prevalence of SCH in obese patients (class II and III) and to observe the behavior of thyroid hormones (TSH, hormone triiodothyronine, thyroxine, free thyroxine) with significant weight loss after RYGB. SETTING: Hospital Nossa Senhora das Graças, Curitiba, Paraná, Brazil. METHODS: We retrospectively reviewed the medical records of 215 obese patients who underwent RYGB between 2005 and 2012 with a follow-up of at least 2 years. The study was observational and descriptive. The selected times for clinical and laboratory evaluations were preoperative, 3, 6, 12, and 24 months after the procedure. Association, correlation, and variance analyses were performed. RESULTS: The prevalence of SCH preoperatively was 9.3%. SCH was corrected in 89.5% of patients 12 months after RYGB. We did not find an association between TSH and BMI (r = .002, P = .971). There was a positive impact of bariatric surgery on all metabolic variables. We showed that serum TSH level had no positive correlation with the presence or absence of metabolic syndrome. CONCLUSIONS: Weight loss after bariatric surgery leads to normalization of TSH levels in most patients and none developed overt hypothyroidism. Obese patients with SCH should not be treated with thyroid hormone replacement. Serial monitoring of thyroid function after obesity therapy seems to be a reasonable approach.

ACR TI-RADS and ATA US scores are helpful for the management of thyroid nodules with indeterminate cytology.

BACKGROUND: Cytologically indeterminate thyroid nodules currently present a challenge for clinical decision-making. The main aim of our study was to determine whether the classifications, American College of Radiology (ACR) TI-RADS and 2015 American Thyroid Association (ATA) guidelines, in association with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), could be used to stratify the malignancy risk of indeterminate thyroid nodules and guide their clinical management. METHODS: The institutional review board approved this retrospective study of a cohort of 140 thyroid nodules in 139 patients who were referred to ultrasound-guided fine-needle aspiration cytology (FNAC) from January 2012 to June 2016 with indeterminate cytological results (44 Bethesda III, 52 Bethesda IV and 44 Bethesda V) and in whom pre-FNAC thyroid US images and histological results after surgery were available. Each included nodule was classified by one radiologist blinded to the cytological and histological diagnoses according to the ACR TIRADS scores and the US patterns as recommended in the 2015 ATA guidelines. The risk of malignancy was estimated for Bethesda, TI-RADS scores, ATA US patterns and their combination. RESULTS: Of the 140 indeterminate thyroid nodules examined, 74 (52.9%) were histologically benign. A different rate of malignancy (p < 0.001) among Bethesda III, IV and V was observed. The rate of malignancy increased according to the US suspicion categories (p < 0.001) in both US classifications (TI-RADS and ATA). Thyroid nodules classified as Bethesda III and the lowest risk US categories (very low, low and intermediate suspicion by ATA and 2, 3 and 4a by TI-RADS) displayed a sensitivity of 95.3% for both classifications and a negative predictive value of 94.3 and 94.1%, respectively. The highest risk US categories (high suspicion by ATA and 4b,4c and 5 by TI-RADS) were significantly associated with cancer (odds ratios [ORs] 14.7 and 9.8, respectively). CONCLUSIONS: Ultrasound classifications, ACR TI-RADS and ATA guidelines, may help guide the management of indeterminate thyroid nodules, suggesting a conservative approach to nodules with low-risk US suspicion and Bethesda III, while molecular testing and surgery should be considered for nodules with high-risk US suspicion and Bethesda IV or V.

Thyroid nodules ≤ 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion

ABSTRACT The indolent evolution of low-risk papillary thyroid microcarcinoma (mPTC) in adult patients and the consequences of thyroidectomy require a revision of the management traditionally recommended. Aiming to spare patients unnecessary procedures and therapies and to optimize the health system in Brazil, we suggest some measures. Fine-needle aspiration of nodules ≤ 1 cm without extrathyroidal extension on ultrasonography should be performed only in nodules classified as "very suspicious" (i.e., high suspicion according to ATA, high risk according to AACE, TI-RADS 5) and in selected cases [age < 40 years, nodule adjacent to the trachea or recurrent laryngeal nerve (RLN), multiple suspicious nodules, presence of hypercalcitoninemia or suspicious lymph nodes]. Active surveillance (AS) rather than immediate surgery should be considered in adult patients with low-risk mPTC. Lobectomy is the best option in patients with unifocal low-risk mPTC who are not candidates for AS because of age, proximity of the tumor to the trachea or RLN, or because they opted for surgery. The same applies to patients who started AS but had a subsequent surgical indication not due to a suspicion of tumor extension beyond the gland or multicentricity. Molecular tests are not necessary to choose between AS and surgery or, in the latter case, between lobectomy and total thyroidectomy. The presence of RAS or other RAS-like mutations or BRAFV600E or other BRAF V600E-like mutations should not modify the management cited above; however, the rare cases of mPTC exhibiting high-risk mutations, like in the TERT promoter or p53, are not candidates for AS.

Thyroid nodules ≤ 1 cm and papillary thyroid microcarcinomas: Brazilian experts opinion.

The indolent evolution of low-risk papillary thyroid microcarcinoma (mPTC) in adult patients and the consequences of thyroidectomy require a revision of the management traditionally recommended. Aiming to spare patients unnecessary procedures and therapies and to optimize the health system in Brazil, we suggest some measures. Fine-needle aspiration of nodules ≤ 1 cm without extrathyroidal extension on ultrasonography should be performed only in nodules classified as "very suspicious" (i.e., high suspicion according to ATA, high risk according to AACE, TI-RADS 5) and in selected cases [age < 40 years, nodule adjacent to the trachea or recurrent laryngeal nerve (RLN), multiple suspicious nodules, presence of hypercalcitoninemia or suspicious lymph nodes]. Active surveillance (AS) rather than immediate surgery should be considered in adult patients with low-risk mPTC. Lobectomy is the best option in patients with unifocal low-risk mPTC who are not candidates for AS because of age, proximity of the tumor to the trachea or RLN, or because they opted for surgery. The same applies to patients who started AS but had a subsequent surgical indication not due to a suspicion of tumor extension beyond the gland or multicentricity. Molecular tests are not necessary to choose between AS and surgery or, in the latter case, between lobectomy and total thyroidectomy. The presence of RAS or other RAS-like mutations or BRAFV600E or other BRAF V600E-like mutations should not modify the management cited above; however, the rare cases of mPTC exhibiting high-risk mutations, like in the TERT promoter or p53, are not candidates for AS.

Genotype and phenotype landscape of MEN2 in 554 medullary thyroid cancer patients: the BrasMEN study.

Multiple endocrine neoplasia type 2 (MEN2) is an autosomal dominant genetic disease caused by RET gene germline mutations that is characterized by medullary thyroid carcinoma (MTC) associated with other endocrine tumors. Several reports have demonstrated that the RET mutation profile may vary according to the geographical area. In this study, we collected clinical and molecular data from 554 patients with surgically confirmed MTC from 176 families with MEN2 in 18 different Brazilian centers to compare the type and prevalence of RET mutations with those from other countries. The most frequent mutations, classified by the number of families affected, occur in codon 634, exon 11 (76 families), followed by codon 918, exon 16 (34 families: 26 with M918T and 8 with M918V) and codon 804, exon 14 (22 families: 15 with V804M and 7 with V804L). When compared with other major published series from Europe, there are several similarities and some differences. While the mutations in codons C618, C620, C630, E768 and S891 present a similar prevalence, some mutations have a lower prevalence in Brazil, and others are found mainly in Brazil (G533C and M918V). These results reflect the singular proportion of European, Amerindian and African ancestries in the Brazilian mosaic genome.

The Kobresia pygmaea ecosystem of the Tibetan highlands - Origin, functioning and degradation of the world's largest pastoral alpine ecosystem: Kobresia pastures of Tibet.

With 450,000 km2Kobresia (syn. Carex) pygmaea dominated pastures in the eastern Tibetan highlands are the world's largest pastoral alpine ecosystem forming a durable turf cover at 3000-6000 m a.s.l. Kobresia's resilience and competitiveness is based on dwarf habit, predominantly below-ground allocation of photo assimilates, mixture of seed production and clonal growth, and high genetic diversity. Kobresia growth is co-limited by livestock-mediated nutrient withdrawal and, in the drier parts of the plateau, low rainfall during the short and cold growing season. Overstocking has caused pasture degradation and soil deterioration over most parts of the Tibetan highlands and is the basis for this man-made ecosystem. Natural autocyclic processes of turf destruction and soil erosion are initiated through polygonal turf cover cracking, and accelerated by soil-dwelling endemic small mammals in the absence of predators. The major consequences of vegetation cover deterioration include the release of large amounts of C, earlier diurnal formation of clouds, and decreased surface temperatures. These effects decrease the recovery potential of Kobresia pastures and make them more vulnerable to anthropogenic pressure and climate change. Traditional migratory rangeland management was sustainable over millennia, and possibly still offers the best strategy to conserve and possibly increase C stocks in the Kobresia turf.

Bacterial Small RNAs in the Genus Herbaspirillum spp.

The genus Herbaspirillum includes several strains isolated from different grasses. The identification of non-coding RNAs (ncRNAs) in the genus Herbaspirillum is an important stage studying the interaction of these molecules and the way they modulate physiological responses of different mechanisms, through RNA⁻RNA interaction or RNA⁻protein interaction. This interaction with their target occurs through the perfect pairing of short sequences (cis-encoded ncRNAs) or by the partial pairing of short sequences (trans-encoded ncRNAs). However, the companion Hfq can stabilize interactions in the trans-acting class. In addition, there are Riboswitches, located at the 5' end of mRNA and less often at the 3' end, which respond to environmental signals, high temperatures, or small binder molecules. Recently, CRISPR (clustered regularly interspaced palindromic repeats), in prokaryotes, have been described that consist of serial repeats of base sequences (spacer DNA) resulting from a previous exposure to exogenous plasmids or bacteriophages. We identified 285 ncRNAs in Herbaspirillum seropedicae (H. seropedicae) SmR1, expressed in different experimental conditions of RNA-seq material, classified as cis-encoded ncRNAs or trans-encoded ncRNAs and detected RNA riboswitch domains and CRISPR sequences. The results provide a better understanding of the participation of this type of RNA in the regulation of the metabolism of bacteria of the genus Herbaspirillum spp.

Clinical outcomes of low and intermediate risk differentiated thyroid cancer patients treated with 30mCi for ablation or without radioactive iodine therapy.

OBJECTIVE: To retrospectively evaluate the outcomes of patients with low and intermediate risk thyroid carcinoma treated with total thyroidectomy (TT) and who did not undergo radioiodine remnant ablation (RRA) and to compare them to patients receiving low dose of iodine (30 mCi). SUBJECTS AND METHODS: A total of 189 differentiated thyroid cancer (DTC) patients treated with TT followed by 30mCi for RRA or not, followed in two referral centers in Brazil were analyzed. RESULTS: From the 189 patients, 68.8% was ATA low-risk, 30.6% intermediate and 0.6% high risk. Eighty-seven patients underwent RRA and 102 did not. The RRA groups tended to be younger and had a higher frequency of extra-thyroidal extension (ETE). RRA did not have and impact on response to initial therapy neither in low (p = 0.24) nor in intermediate risk patients (p = 0.66). It also had no impact on final outcome and most patients had no evidence of disease (NED) at final follow-up. Recurrence/persistence of disease was found in 1.2% of RRA group and 2% in patients treated only with TT (p = 0.59). CONCLUSIONS: Our study shows that in low and intermediate-risk patients, RRA with 30 mCi seems to have no major advantage over patients who did not undergo RRA regarding response to initial therapy in each risk group and also in long term outcomes.

East Asian Winter Monsoon Impacts the ENSO-related Teleconnections and North American Seasonal Air Temperature Prediction.

El Niño-Southern Oscillation (ENSO) is a key feature for seasonal weather and climate prediction in the extra-tropics since related sea surface temperature anomalies induce precipitation anomalies that generate poleward propagating Rossby waves and teleconnections. The East Asian winter monsoon (EAWM) is driven by processes originating over the Asian continent and, to a lesser degree, by ENSO-related tropical convection. EAWM also strongly affects convection and precipitation patterns over the western tropical Pacific by cold air outbreaks reaching equatorial latitudes. Hence, one can expect a modulating effect of EAWM on the generation of Rossby wave trains related to ENSO. By increasing the convective heating over the western Pacific, strong EAWM strengthens the Pacific Walker circulation, and weakens (strengthens) the El Niño (La Niña) related effects on the extra-tropics via a modulation of the Pacific North America teleconnection pattern. Our results indicate that, for seasonal prediction over North America, along with ENSO the variability of EAWM should also be taken into account. The climate anomalies over the North America for the same phase of ENSO are significantly different for strong and weak EAWM.

MANAGEMENT OF ENDOCRINE DISEASE: Pitfalls on the replacement therapy for primary and central hypothyroidism in adults.

Hypothyroidism is one of the most common hormone deficiencies in adults. Most of the cases, particularly those of overt hypothyroidism, are easily diagnosed and managed, with excellent outcomes if treated adequately. However, minor alterations of thyroid function determine nonspecific manifestations. Primary hypothyroidism due to chronic autoimmune thyroiditis is largely the most common cause of thyroid hormone deficiency. Central hypothyroidism is a rare and heterogeneous disorder characterized by decreased thyroid hormone secretion by an otherwise normal thyroid gland, due to lack of TSH. The standard treatment of primary and central hypothyroidism is hormone replacement therapy with levothyroxine sodium (LT4). Treatment guidelines of hypothyroidism recommend monotherapy with LT4 due to its efficacy, long-term experience, favorable side effect profile, ease of administration, good intestinal absorption, long serum half-life and low cost. Despite being easily treatable with a daily dose of LT4, many patients remain hypothyroid due to malabsorption syndromes, autoimmune gastritis, pancreatic and liver disorders, drug interactions, polymorphisms in DIO2 (iodothyronine deiodinase 2), high fiber diet, and more frequently, non-compliance to LT4 therapy. Compliance to levothyroxine treatment in hypothyroidism is compromised by daily and fasting schedule. Many adult patients remain hypothyroid due to all the above mentioned and many attempts to improve levothyroxine therapy compliance and absorption have been made.