from rag_fact_checker.data import Config
from rag_fact_checker.pipeline.pipeline_prompt import PipelinePrompt


class PipelineDemonstration(PipelinePrompt):
    def __init__(self, config: Config):
        super().__init__(config)

    @property
    def default_demo_output(self) -> str:
        return ""

    def get_demo_data(self, demo_type: str = "triplet_generator") -> str:
        return getattr(self, f"demo_{demo_type}")

    @property
    def demo_triplet_generator(self) -> str:
        return """[BEGIN FEW-SHOT-EXAMPLES]
        <Example 0 Input/Output Pair>
        Input:
        Input Text: Iodine thyroid blocking (ITB) is a protective measure used to reduce the risk of developing thyroid cancer following exposure to radioactive iodine, particularly in the context of a nuclear accident. It involves administering high doses of potassium iodide to block the uptake of radioiodine by the thyroid gland. This intervention is especially important in situations where there is a release of radioiodine into the atmosphere, as it can help prevent the long-term health consequences associated with thyroid cancer. The effectiveness of ITB has been recognized, but potential adverse effects have not been systematically investigated, leading to a weak evidence base regarding its safety.
        Output:
        [["Iodine thyroid blocking (ITB)", "is", "a protective measure used to reduce the risk of developing thyroid cancer following exposure to radioactive iodine in the context of a nuclear accident"], ["Iodine thyroid blocking (ITB)", "involves", "administering high doses of potassium iodide to block the uptake of radioiodine by the thyroid gland"], ["Iodine thyroid blocking (ITB)", "is especially important in", "situations where there is a release of radioiodine into the atmosphere"], ["Iodine thyroid blocking (ITB)", "can help prevent", "the long-term health consequences associated with thyroid cancer"], ["The effectiveness of iodine thyroid blocking (ITB)", "has been recognized, but", "potential adverse effects have not been systematically investigated"], ["The lack of systematic investigation of potential adverse effects", "has led to", "a weak evidence base regarding the safety of iodine thyroid blocking (ITB)"]]
        
        
        
        <Example 1 Input/Output Pair>
        Input:
        Input Text: Thyroid hormone therapy may be indicated in patients with heart failure, particularly in those with low triiodothyronine (T3) levels or subclinical hypothyroidism. Clinical studies have shown that thyroid hormone replacement, such as synthetic L-T3, can improve cardiac function and neuroendocrine profiles without significant adverse effects, including increased heart rate. Additionally, thyroid hormone or its analogs have demonstrated potential benefits in enhancing myocardial performance and improving symptoms in heart failure patients. However, further controlled trials are necessary to evaluate the long-term safety and efficacy of such treatments in this population.
        Output:
        [["Thyroid hormone therapy", "may be indicated in", "patients with heart failure, particularly in those with low triiodothyronine (T3) levels or subclinical hypothyroidism"], ["Clinical studies", "have shown that", "thyroid hormone replacement, such as synthetic L-T3, can improve cardiac function and neuroendocrine profiles without significant adverse effects, including increased heart rate"], ["Thyroid hormone or its analogs", "have demonstrated potential benefits in", "enhancing myocardial performance and improving symptoms in heart failure patients"], ["Further controlled trials", "are necessary to evaluate", "the long-term safety and efficacy of thyroid hormone therapy in patients with heart failure"]]
        
        
        
        <Example 2 Input/Output Pair>
        Input:
        Input Text: Thyrocyte destruction in autoimmune thyroiditis, specifically Hashimoto"s thyroiditis, is primarily induced through Fas-mediated mechanisms. The interaction between thyrocyte Fas and Fas ligand (FasL) is proposed as a major mechanism for thyrocyte depletion. During the active phases of Hashimoto"s thyroiditis, autocrine/paracrine interactions of Fas and FasL lead to the death of thyrocytes. While infiltrating T lymphocytes (ITL) express high levels of Fas, they do not produce significant amounts of FasL, indicating that they are not directly responsible for the destruction of thyrocytes. Instead, the Fas-FasL system plays a crucial role in dictating the outcome of the autoimmune response, leading to the destruction of thyrocytes through the activation of apoptotic pathways.
        Output:
        [["thyrocyte destruction in autoimmune thyroiditis, specifically Hashimoto"s thyroiditis", "is primarily induced through", "Fas-mediated mechanisms"], ["the interaction between thyrocyte Fas and Fas ligand (FasL)", "is proposed as", "a major mechanism for thyrocyte depletion"], ["autocrine/paracrine interactions of Fas and FasL during the active phases of Hashimoto"s thyroiditis", "lead to", "the death of thyrocytes"], ["infiltrating T lymphocytes (ITL)", "express", "high levels of Fas"], ["infiltrating T lymphocytes (ITL)", "do not produce", "significant amounts of FasL"], ["the Fas-FasL system", "plays a crucial role in", "dictating the outcome of the autoimmune response"], ["the activation of apoptotic pathways", "leads to", "the destruction of thyrocytes"]]
        
        
        
        [END FEW-SHOT-EXAMPLES]
        """

    @property
    def demo_fact_checker(self) -> str:
        return """[BEGIN FEW-SHOT-EXAMPLES]

        <Example 1 Input/Output Pair>
        Input:
        Input Triplets:\n0: ['Thyroid hormone receptor beta1 (TR-beta1)', 'enhances', 'ChREBP gene expression via LXRE2']\n-1: ['TR-beta1', 'boosts', 'T3-mediated lipogenesis in the liver']\n-2: ['TR-beta1', 'modulates', 'other metabolic genes such as P450R']\n-3: ['TR-beta1', 'underscores', 'broader influence on hepatic metabolism']\n-4: ['TR-beta1', 'plays a key role in', 'regulating lipid metabolism pathways']\n\nSource Triplets:\n0: ['carbohydrate response element-binding protein (ChREBP) and sterol response element-binding protein (SREBP)-1c', 'are regulated by', 'liver X receptors (LXRs)']\n-1: ['ChREBP and SREBP-1c', 'play central roles in', 'hepatic lipogenesis']\n-2: ['liver X receptors (LXRs) and thyroid hormone receptors (TRs)', 'influence', 'each other’s transcriptional activity']\n-3: ['researchers', 'investigated whether', 'TRs control ChREBP expression']\n-4: ['thyroid hormone (T3) and TR-beta1', 'upregulate', 'ChREBP']\n-5: ['thyroid hormone (T3) and TR-beta1', 'upregulate ChREBP by binding', 'direct repeat-4 elements (LXRE1/2)']\n-6: ['thyroid hormone (T3) and TR-beta1', 'fine-tune', 'hepatic lipid metabolism']
        
        [REFERRED TRIPLETS]
        Output:
        triplet_idx_0: (source triplets #4, #5) → The source triplets confirm that TR-beta1 upregulates ChREBP by binding to LXRE1/2, which supports the input triplet's claim about enhancing ChREBP gene expression via LXRE2.
        triplet_idx_-1: (source triplet #6) → Source triplet #6 states that TR-beta1 fine-tunes hepatic lipid metabolism, which can be inferred to include boosting T3-mediated lipogenesis in the liver.
        triplet_idx_-2: None → There is no source triplet that specifically mentions TR-beta1 modulating other metabolic genes such as P450R.
        triplet_idx_-3: (source triplet #6) → Source triplet #6 indicates that TR-beta1 fine-tunes hepatic lipid metabolism, which implies a broader influence on hepatic metabolism.
        triplet_idx_-4: (source triplet #6) → Source triplet #6 states that TR-beta1 fine-tunes hepatic lipid metabolism, supporting the input triplet's claim about regulating lipid metabolism pathways.
        
        [FINAL ANSWER]
        triplet_idx_0:True
        triplet_idx_-1:True
        triplet_idx_-2:False
        triplet_idx_-3:True
        triplet_idx_-4:True
        
        
        [END FEW-SHOT-EXAMPLES]"""

    @property
    def demo_hallucination_data_generator(self) -> str:
        return """[BEGIN FEW-SHOT-EXAMPLES]
        <Example 0 Input/Output Pair>
        Input:\nDirections:\nFollow the instructions\n\nReference Document:\nMutations in NKX2-1 cause neurological, pulmonary, and thyroid hormone impairment. Recently, the disease was named brain-lung-thyroid syndrome. Here, we report three patients with brain-lung-thyroid syndrome. All patients were unable to walk until 24 months of age, and still have a staggering gait, without mental retardation. They have also had choreoathetosis since early infancy. Genetic analysis of NKX2-1 revealed a novel missense mutation (p.Val205Phe) in two patients who were cousins and their maternal families, and a novel 2.6-Mb deletion including NKX2-1 on chromosome 14 in the other patient. Congenital hypothyroidism was not detected on neonatal screening in the patient with the missense mutation, and frequent respiratory infections were observed in the patient with the deletion in NKX2-1. Oral levodopa did not improve the gait disturbance or involuntary movement. The results of (99m)Tc-ECD single-photon emission computed tomography (ECD-SPECT) analyzed using the easy Z-score imaging system showed decreased cerebral blood flow in the bilateral basal ganglia, especially in the caudate nuclei, in all three patients, but no brain magnetic resonance imaging (MRI) abnormalities. These brain nuclear image findings indicate that NKX2-1 haploinsufficiency causes dysfunction of the basal ganglia, especially the caudate nuclei, resulting in choreoathetosis and gait disturbance in this disease.\n- Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations. We report the clinical and molecular characteristics of four cases presenting with primary hypothyroidism, respiratory distress, and neurological disorder. Two of the four patients presenting with the triad of BLTS had NKX2-1 mutations, and one of these NKX2-1 [c.890_896del (p.Ala327Glyfs*52)] is a novel variant. The third patient without any identified NKX2-1 mutations was a carrier of mitochondrial mutation; this raises the possibility of mitochondrial mutations contributing to thyroid dysgenesis. Although rare, the triad of congenital hypothyroidism, neurological, and respiratory signs is highly suggestive of NKX2-1 anomalies. Screening for NKX2-1 mutations in patients with thyroid, lung, and neurological abnormalities will enable a unifying diagnosis and genetic counseling for the affected families. In addition, identification of an NKX2-1 defect would be helpful in allaying the concerns about inadequate thyroxine supplementation as the cause of neurological defects observed in some children with congenital hypothyroidism.\n- AIM: Benign hereditary chorea is a dominantly inherited, childhood-onset hyperkinetic movement disorder characterized by non-progressive chorea and variable degrees of thyroid and respiratory involvement. Loss-of-function mutations in NKX2.1, a gene vital to the normal development and function of the brain, lungs, and thyroid, have been identified in a number of individuals.METHOD: Clinical data from individuals with benign hereditary chorea identified through paediatric neurology services were collected in a standardized format. The NKX2.1 gene was analysed by Sanger sequencing, multiplex ligation-dependent probe amplification, and microarray analysis.RESULTS: Six of our cohort were female and four male, median age at assessment was 8 years 6 months (range 1 y 6 mo-18 y). We identified 10 probands with NKX2.1 mutations; nine of these mutations are novel (including two whole-gene deletions) and one has been previously reported. Of the 10 individuals, eight presented with muscle hypotonia and four had evidence of hypothyroidism or respiratory involvement. Only three out of the 10 individuals had the full triad of 'brain-lung-thyroid syndrome' symptoms. Additional clinical characteristics occurring in individual participants included growth hormone deficiency, pes cavus, kyphosis, duplex kidney, and obsessive-compulsive disorder.INTERPRETATION: Our data suggest that the neurological phenotype is prominent in this condition and that many patients with benign hereditary chorea do not have the classic triad of brain-lung-thyroid syndrome. The extended phenotype may include obsessive-compulsive disorder and skeletal abnormalities.\n- OBJECTIVES: To verify the involvement of NKX2-1 gene in infants with brain-lung-thyroid (BLT) syndrome and hypothyroid phenotypes variable among congenital hypothyroidism (CH) or idiopathic mild hypothyroidism (IMH) of postnatal onset.METHODS: The candidates were selected by a case-finding approach in 130 CH and 53 IMH infants. The NKX2-1 gene was analyzed by direct sequencing and multiplex ligation-dependent probe amplification. The variants were studied in vitro, by expression analyses and luciferase bioassay.RESULTS: Four cases (3 CH and 1 IMH) consistent with BLT syndrome were identified. Two children were affected with respiratory distress and CH, but wild-type NKX2-1 gene. The remaining two presented choreic movements and no pulmonary involvement, but discrepant thyroid phenotypes: one had severe CH with lingual ectopy and the other one IMH with gland in situ. They were carriers of new de novo heterozygous frameshift mutations of NKX2-1 (c.177delG and c.153_166del14). The c.177delG leads to a prematurely truncated protein (p.H60TfsX11) with undetectable activity in vitro. The c.153_166del14 leads to the generation of an elongated aberrant protein (p.A52RfsX351) able to translocate into the nucleus, but completely inactive on a responsive promoter.CONCLUSIONS: Two novel heterozygous frameshift mutations of NKX2-1 were identified in 2 cases selected on the basis of a BLT-like phenotype among 183 hypothyroid infants. The atypical hypothyroid phenotypes of these 2 children (CH with lingual ectopy or IMH of postnatal onset) further expand the clinical spectrum that can be associated with NKX2-1 mutations.\n- Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). The objectives of the present study were (i) detection of NKX2-1 mutations in patients with CH associated with pneumopathy and/or BHC, (ii) functional analysis of new mutations in vitro and (iii) description of the phenotypic spectrum of brain-lung-thyroid syndrome. We identified three new heterozygous missense mutations (L176V, P202L, Q210P), a splice site mutation (376-2A-->G), and one deletion of NKX2-1 at 14q13. Functional analysis of the three missense mutations revealed loss of transactivation capacity on the human thyroglobulin enhancer/promoter. Interestingly, we showed that deficient transcriptional activity of NKX2-1-P202L was completely rescued by cotransfected PAX8-WT, whereas the synergistic effect was abolished by L176V and Q210P. The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%). Thyroid morphology was normal (55%) and compensated hypothyroidism occurred in 61%. Lung disease occurred in 54% of patients (IRDS at term 76%; recurrent pulmonary infections 24%). On follow-up, 20% developed severe chronic interstitial lung disease, and 16% died. In conclusion, we describe five new NKX2.1 mutations with, for the first time, complete rescue by PAX8 of the deficient transactivating capacity in one case. Additionally, our review shows that the majority of affected patients display neurological and/or thyroidal problems and that, although less frequent, lung disease is responsible for a considerable mortality.\n- BACKGROUND: NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease.AIMS AND METHODS: We evaluated the recently developed Multiplex Ligation-dependent Probe Amplification (MLPA) method to assess the relative copy number of genes. The goal was to determine if MLPA could improve, in addition to direct sequencing, the detection rate of NKX2.1 mutations in a phenotype-selected cohort of 24 patients affected by neurological, thyroid and/or pulmonary disorders.RESULTS: Direct sequencing revealed two heterozygous mutations. Using MLPA, we identified two further heterozygous NKX2.1 gene deletions. MLPA increased the detection rate by 50%. All patients with gene deletions identified were affected by BHC and congenital hypothyroidism.CONCLUSION: MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. All patients with an NKX2.1 mutation had BHC and congenital hypothyroidism, emphasizing the high prevalence of these signs associated with defective NKX2.1 alleles.\n\n(Optional) Few-Shot Demonstrations:\nIf few-shot examples are provided here, they will look like this:\n\n[BEGIN FEW-SHOT-EXAMPLES]\n<Example 1 Input/Output Pair>\n<Example 2 Input/Output Pair>\n\u2026\n[END FEW-SHOT-EXAMPLES]\n\nIf these examples are present, incorporate their style and approach into your solution.\n\n\nQuestion:\nMutation of which gene is implicated in the Brain-lung-thyroid syndrome?\n\nOutput:\nNon-Hallucinated Answer:\nThe gene implicated in Brain-lung-thyroid syndrome (BLTS) is NKX2-1, also known as thyroid transcription factor 1 (TTF1). Mutations in this gene are responsible for the syndrome, which is characterized by a triad of symptoms: congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea. Evidence from various studies indicates that NKX2-1 mutations lead to dysfunction in the development and function of the brain, lungs, and thyroid. For instance, one study reported three patients with BLTS who exhibited a novel missense mutation (p.Val205Phe) in NKX2-1, while another patient had a 2.6-Mb deletion of the gene. These mutations were associated with neurological symptoms such as choreoathetosis and gait disturbances, as well as respiratory issues and thyroid hormone impairment. Furthermore, screening for NKX2-1 mutations in patients presenting with thyroid, lung, and neurological abnormalities is crucial for accurate diagnosis and genetic counseling, as it can help clarify the underlying causes of these symptoms and guide treatment options.\n\nHallucinated Answer:\nThe gene implicated in Brain-lung-thyroid syndrome (BLTS) is NKX2-1, also known as thyroid transcription factor 1 (TTF1). Mutations in this gene are responsible for the syndrome, which is characterized by a triad of symptoms: congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea. Evidence from various studies indicates that NKX2-1 mutations lead to dysfunction in the development and function of the brain, lungs, and thyroid. For instance, one study reported three patients with BLTS who exhibited a novel missense mutation (p.Val205Phe) in NKX2-1, while another patient had a 2.6-Mb deletion of the gene. These mutations were associated with neurological symptoms such as choreoathetosis and gait disturbances, as well as respiratory issues and thyroid hormone impairment. *Interestingly, one of the patients was also found to have a rare mitochondrial disorder that was unrelated to NKX2-1 mutations.* Furthermore, screening for NKX2-1 mutations in patients presenting with thyroid, lung, and neurological abnormalities is crucial for accurate diagnosis and genetic counseling, as it can help clarify the underlying causes of these symptoms and guide treatment options. *In a separate case, a patient with a similar presentation was treated with a novel gene therapy that had not yet been approved for use in humans.*\n\nHallucinated Details:\n\t\u2022\tOne of the patients was also found to have a rare mitochondrial disorder that was unrelated to NKX2-1 mutations.\n\t\u2022\tA patient with a similar presentation was treated with a novel gene therapy that had not yet been approved for use in humans.
        
        
        <Example 1 Input/Output Pair>
        Input:\n\nReference Document:\nThe PTEN (MMAC1/TEP1) tumor suppressor gene was recently isolated and mapped to human chromosome band 10q23. Homozygous deletions and mutations of PTEN were observed in cell lines and sporadic cancers of the breast, kidney, and central nervous system. Germline mutations in PTEN were recently found in Cowden disease, an autosomal dominant inherited syndrome, previously mapped to chromosome bands 10q22-23. This disease is associated with a wide variety of malignancies and hamartomas of ectodermal, mesodermal, and endodermal origin. The most common neoplasms in Cowden disease patients arise in the breast, skin, and thyroid (follicular subtype). To determine the involvement of PTEN in sporadic follicular thyroid tumors, we first analyzed sporadic follicular adenomas and carcinomas for deletions of the PTEN gene. Loss of heterozygosity was found in 7/26 (27%) follicular carcinomas and 2/27 (7%) follicular adenomas, one of which was a small hemizygous deletion (approximately 3 cm). Sequence analysis of the entire PTEN coding region revealed two mutations in carcinomas with 10q loss. Our findings suggest that the PTEN tumor suppressor gene is occasionally inactivated in sporadic follicular thyroid tumors.\n- Germline mutations in the tumor-suppressor gene PTEN (MMAC1, TEP1) are found in Cowden syndrome, which predisposes to hamartomas, breast cancer, trichilemmomas, and thyroid tumors of follicular epithelium. PTEN has also been found to be somatically deleted, mutated, and/or silenced in various sporadically occurring cancers such as glioblastoma, breast cancer, kidney cancer, malignant melanoma, and endometrial cancer. Loss or reduction of PTEN protein expression as well as inappropriate subcellular compartmentalization is seen in non-medullary thyroid cancers. However, although allelic loss of the PTEN locus in 10q23.3 is frequently seen, this is not coupled with mutations in the PTEN gene. To approach further the frequency and mechanism behind PTEN silencing, we screened a panel of 87 sporadic thyroid tumors for PTEN mRNA expression, including 14 anaplastic carcinomas, 37 follicular carcinomas, 21 atypical adenomas, and 15 ordinary adenomas. Complete loss of PTEN mRNA expression was evident in six of the tumors, including four anaplastic carcinomas, one widely invasive carcinoma, and one ordinary adenoma. The transcriptional silencing of PTEN was significantly associated with the anaplastic subtype, suggesting that PTEN is involved in the carcinogenesis of highly malignant or late-stage thyroid cancers, whereas this particular mechanism appears to be of minor importance in differentiated follicular thyroid tumors. No association was observed between the expression, loss of heterozygosity, and mutation status in the 33 cases in which these parameters were compared. This indicates that PTEN silencing is a result of a wide variety of epigenetic and/or structural silencing mechanisms rather than a consequence of structural biallelic inactivation of the classical type. Furthermore, the high rate of alterations in the 10q23 region might indicate the presence of an as-yet unknown tumor-suppressor gene with an important role in the development of thyroid tumors.\n- Various genes have been identified to play a role in the pathogenesis of follicular thyroid tumors. Cowden syndrome is the only known familial syndrome with an increased risk of both follicular thyroid adenoma (FA) and carcinoma (FTC). Germline mutations in the tumor suppressor gene PTEN, which encodes a dual-specificity phosphatase, have been found in up to 80% of patients with Cowden syndrome suggesting a role of PTEN in the pathogenesis of follicular thyroid tumors. Although somatic intragenic mutations in PTEN, which maps to 10q23.3, are rarely found in follicular tumors, loss of heterozygosity (LOH) of markers within 10q22-24 occurs in about 25%. Recently, another phosphatase gene, MINPP1, has been localized to 10q23.3. MINPP1 has the ability to remove 3-phosphate from inositol phosphate substrates, a function that overlaps that of PTEN. Because of this overlapping function with PTEN and the physical location of MINPP1 to a region with frequent LOH in follicular thyroid tumors, we considered it to be an excellent candidate gene that could contribute to the pathogenesis of follicular thyroid tumors. We analyzed DNA from tumor and corresponding normal tissue from 23 patients with FA and 15 patients with FTC for LOH and mutations at the MINPP1 locus. LOH was identified in four malignant and three benign tumors. One of these FTCs with LOH was found to harbor a somatic c.122C > T or S41L mutation. We also found two germline sequence variants, c.809A > G (Q270R) and IVS3 + 34T > A. The c.809A > G variant was found in only one patient with FA but not in patients with FTC or normal controls. More interestingly, IVS3 + 34T > A was found in about 15% of FA cases and normal controls but not in patients with FTC. These results suggest a role for MINPP1 in the pathogenesis of at least a subset of malignant follicular thyroid tumors, and MINPP1 might act as a low penetrance predisposition allele for FTC.\n- BACKGROUND: Differentiated thyroid cancer (DTC) is seen in 3%-10% of individuals carrying a germline PTEN mutation. Patients with PTEN mutations are at risk for additional neoplasms as are their affected offspring. However, the frequency of PTEN mutations among DTC cases has not been systematically analyzed. The objective of this study was to determine the frequency of PTEN mutations in an unselected group of patients with DTC and to identify whether additional clinical features might indicate the need for referral for genetic counseling and possible testing.METHODS: We collected personal medical and family history information, head circumference data, and blood from 259 consecutively identified clinic-based patients with DTC, unselected for personal or family history. Individuals were categorized for diagnostic criteria for Cowden syndrome (CS) using the 2009 National Comprehensive Cancer Network (NCCN) guidelines and underwent germline PTEN mutation analysis.RESULTS: Two of the 259 patients (0.8%), with both follicular thyroid carcinoma and macrocephaly, were found to carry a germline mutation in the PTEN gene. The PTEN mutation frequency in unselected cases of follicular thyroid carcinoma was 4.8%.CONCLUSION: The frequency of germline pathogenic PTEN mutations in an unselected series of patients with DTC is relatively low, but it is enriched by considering follicular histology and macrocephaly. These results suggest that by adding head circumference to the clinical assessment, thyroid cancer specialists can more effectively identify patients needing referral for cancer genetic services.\n- Cowden syndrome (CS) or multiple hamartoma syndrome (MIM 158350) is an autosomal dominant disorder with an increased risk for breast and thyroid carcinoma. The diagnosis of CS, as operationally defined by the International Cowden Consortium, is made when a patient, or family, has a combination of pathognomonic major and/or minor criteria. The CS gene has recently been identified as PTEN, which maps at 10q23.3 and encodes a dual specificity phosphatase. PTEN appears to function as a tumour suppressor in CS, with between 13-80% of CS families harbouring germline nonsense, missense, and frameshift mutations predicted to disrupt normal PTEN function. To date, only a small number of tumour suppressor genes, including BRCA1, BRCA2, and p53, have been associated with familial breast or breast/ovarian cancer families. Given the involvement of PTEN in CS, we postulated that PTEN was a likely candidate to play a role in families with a \"CS-like\" phenotype, but not classical CS. To answer these questions, we gathered a series of patients from families who had features reminiscent of CS but did not meet the Consortium Criteria. Using a combination of denaturing gradient gel electrophoresis (DGGE), temporal temperature gel electrophoresis (TTGE), and sequence analysis, we screened 64 unrelated CS-like subjects for germline mutations in PTEN. A single male with follicular thyroid carcinoma from one of these 64 (2%) CS-like families harboured a germline point mutation, c.209T-->C. This mutation occurred at the last nucleotide of exon 3 and within a region homologous to the cytoskeletal proteins tensin and auxilin. We conclude that germline PTEN mutations play a relatively minor role in CS-like families. In addition, our data would suggest that, for the most part, the strict International Cowden Consortium operational diagnostic criteria for CS are quite robust and should remain in place.\n\n(Optional) Few-Shot Demonstrations:\nIf few-shot examples are provided here, they will look like this:\n\n[BEGIN FEW-SHOT-EXAMPLES]\n<Example 1 Input/Output Pair>\n<Example 2 Input/Output Pair>\n\u2026\n[END FEW-SHOT-EXAMPLES]\n\nIf these examples are present, incorporate their style and approach into your solution.\n\n\nQuestion:\nIs PTEN involved in follicular thyroid carcinoma?\n\nOutput:\nNon-Hallucinated Answer:\nPTEN is indeed involved in follicular thyroid carcinoma (FTC). The PTEN gene, which is a tumor suppressor gene located on chromosome 10q23, has been implicated in various cancers, including thyroid tumors. Research indicates that germline mutations in PTEN are found in Cowden syndrome, a hereditary condition that increases the risk of developing several types of tumors, including breast and thyroid cancers. In patients with Cowden syndrome, up to 80% exhibit mutations in the PTEN gene, suggesting a significant role for PTEN in the pathogenesis of follicular thyroid tumors.\n\nIn sporadic cases, studies have shown that loss of heterozygosity (LOH) at the PTEN locus occurs in about 25% of follicular thyroid tumors, although somatic mutations in PTEN are rarely found. A study analyzing sporadic follicular adenomas and carcinomas revealed that loss of heterozygosity was present in 27% of follicular carcinomas and 7% of follicular adenomas. Additionally, complete loss of PTEN mRNA expression was observed in several tumors, particularly in anaplastic carcinomas, indicating that PTEN silencing may contribute to the progression of more aggressive thyroid cancers.\n\nFurthermore, the frequency of germline pathogenic PTEN mutations in unselected cases of differentiated thyroid cancer (DTC) is relatively low, but it is enriched in cases with follicular histology. This suggests that while PTEN mutations are not the predominant cause of FTC, they do play a role in a subset of cases, particularly in those associated with Cowden syndrome or other risk factors.\n\nOverall, the evidence supports the involvement of PTEN in follicular thyroid carcinoma, particularly through mechanisms of gene silencing and loss of heterozygosity, which may contribute to the development and progression of this type of cancer.\n\nHallucinated Answer:\nPTEN is indeed involved in follicular thyroid carcinoma (FTC). The PTEN gene, which is a tumor suppressor gene located on chromosome 10q23, has been implicated in various cancers, including thyroid tumors. Research indicates that germline mutations in PTEN are found in Cowden syndrome, a hereditary condition that increases the risk of developing several types of tumors, including breast and thyroid cancers. In patients with Cowden syndrome, up to 80% exhibit mutations in the PTEN gene, suggesting a significant role for PTEN in the pathogenesis of follicular thyroid tumors.\n\nIn sporadic cases, studies have shown that loss of heterozygosity (LOH) at the PTEN locus occurs in about 25% of follicular thyroid tumors, although somatic mutations in PTEN are rarely found. A study analyzing sporadic follicular adenomas and carcinomas revealed that loss of heterozygosity was present in 27% of follicular carcinomas and 7% of follicular adenomas, one of which was a small hemizygous deletion (approximately 3 cm) that was later found to be associated with a rare form of thyroiditis. Additionally, complete loss of PTEN mRNA expression was observed in several tumors, particularly in anaplastic carcinomas, indicating that PTEN silencing may contribute to the progression of more aggressive thyroid cancers.\n\nFurthermore, the frequency of germline pathogenic PTEN mutations in unselected cases of differentiated thyroid cancer (DTC) is relatively low, but it is enriched in cases with follicular histology. This suggests that while PTEN mutations are not the predominant cause of FTC, they do play a role in a subset of cases, particularly in those associated with Cowden syndrome or other risk factors. Interestingly, a recent study also suggested that the presence of macrocephaly could be a potential indicator for PTEN mutation screening.\n\nOverall, the evidence supports the involvement of PTEN in follicular thyroid carcinoma, particularly through mechanisms of gene silencing and loss of heterozygosity, which may contribute to the development and progression of this type of cancer.\n\nHallucinated Details:\n- The small hemizygous deletion (approximately 3 cm) was later found to be associated with a rare form of thyroiditis, a condition that was previously thought to be unrelated.\n- The presence of macrocephaly was suggested as a potential indicator for PTEN mutation screening, a condition that was previously thought to be unrelated to thyroid cancer.
        
        
        <Example 2 Input/Output Pair>
        Input:\nDirections:\nFollow the instructions\n\nReference Document:\nNew data on viruses isolated from patients with subacute thyroiditis de Quervain are reported. Characteristic morphological, cytological, some physico-chemical and biological features of the isolated viruses are described. A possible role of these viruses in human and animal health disorders is discussed. The isolated viruses remain unclassified so far.\n- We describe a case of quick recovery of myocardium damage in a 15-year-old adolescent with subacute thyroiditis. After 1 week of admission, his cardiovascular status began to show signs of improvement accompanied by the recovery of electrocardiogram and indicators of myocardial damage. We speculate that myocardium damage associated with subacute thyroiditis is a complication of common virus, although we did not detect any abnormal virus antibody and deoxyribonucleic acid in the patient's serum.\n- Subacute thyroiditis is a rare disease in childhood and is considered postviral in origin. Epstein-Barr virus (EBV) involvement has been suspected, but just once demonstrated in an adult female. We report a case of subacute thyroiditis during infectious mononucleosis in a 3-year-old girl. The diagnosis of infectious mononucleosis was supported, in addition to the typical clinical symptoms, by presence of EBV DNA both in plasma and leukocytes. Subacute thyroiditis was diagnosed based on elevated thyroid hormone levels with thyrotropin (TSH) suppression, high inflammation markers and almost absent (99)TC uptake by thyroid. Moreover after 3 months from diagnosis thyroid function went back to normal as well as the (99)TC uptake.\n- The author experienced a case of subacute thyroiditis (de Quervain) in a 36-year-old female. Electron microscopic examination of the thyroid tissue of the patient revealed virus-like particles (VLP) in the degenerated follicular epithelium Judging from the size, the VLP corresponded to the influenza or mumps virus.\n- de Quervain thyroiditis, also known as subacute thyroiditis, is a self-limited inflammatory disease of the thyroid gland. It is extremely rare in children. The hallmarks for diagnosis are painful thyroid enlargement, elevated inflammatory markers, and decreased uptake of the thyroid gland on thyroid scintigraphy. Viral infection has been proposed to be associated with de Quervain thyroiditis. Coxsackie virus has been reported to be one of the viruses associated with the disease. To our knowledge, childhood de Quervain thyroiditis associated with hand-foot-mouth disease caused by coxsackie infection has never been reported. We report a 2.7-year-old boy who presented with typical features of de Quervain thyroiditis following hand-foot-mouth disease caused by coxsackie B4 infection. He had a brief thyrotoxic phase initially, followed by transient hypothyroid phase and euthyroidism thereafter. His thyroid scintigraphy showed a typical faint uptake at the diagnosis, and an improvement of the thyroid scan and uptake was shown 8 weeks later. He was treated with prednisolone and nearly complete resolution was documented within 2 months. Careful evaluation of the patient led to the correct diagnosis and appropriate management.\n- Virological and serological methods were used in examination of 28 patients suffering from subacute thyroiditis de Quervain. Attempts to isolate a presumed viral agent from 8 patients were performed by inoculation of serum, urine, and aspiration biopsies of thyroid glands taken at different stages of the illness, into tissue cultures of different types of human and animal cells. Recovery of a cytopathic viral agent on cells of a rabbit lung continuous line was successful in 5 cases. Serological cross reactions exist between the isolated viruses and patient serum but not with serum of healthy people. Cases with the acquired illness and positive antibodies against the isolated viruses who had been in close and prolonged contact with patients suffering from subacute thyroiditis de Quervain were also investigated.\n- Subacute (de Quervain's) thyroiditis is a rare but important cause of fever of unknown origin. Most cases of subacute thyroiditis are caused by a variety of viruses, for example, Coxsackie, cytomegalovirus, Epstein-Barr virus, and adenovirus. Influenza immunization or infection may cause subacute thyroiditis. We present the first reported case of a fever of unknown origin due to seasonal influenza A in a 67-year-old woman.\n- The etiology of subacute granulomatous thyroiditis (SAT) is obscure, although it is postulated to be associated with viral infections and genetic factors. In the present study, the possibility of an infectious etiology was prospectively studied in 27 consecutive patients with SAT. Special emphasis was put on the role of enteroviruses. Coupled sera (interval one month) were taken from all patients and single sera from 29 control subjects for virus antibody determinations. Stool samples were collected for virus isolation and fine-needle aspiration samples from thyroid gland for the detection of enterovirus RNA using RT-PCR were taken from SAT patients. Enteroviral antibodies were tested using three different methods: indirect EIA, heavy chain capture RIA, and standard complement fixation (CF) test. Antibodies against other common viral pathogens, including enteroviruses, were screened using the CF test and those against Mycoplasma pneumoniae and Chlamydia pneumoniae using EIA and microimmunofluorescence techniques, respectively. Common respiratory viruses were also screened from nasopharyngeal suction samples by antigen detection EIA. Based on serological findings, one patient had acute Cytomegalovirus infection. All other patients were negative in antibody tests, virus isolation, RT-PCR, and antigen detection. Enterovirus RNA was not detected by PCR in the thyroid tissue in any of the fine-needle aspiration samples. There was no evidence of recent enteroviral infections in SAT patients. The results suggest that SAT is not usually associated with acute infections. No evidence was obtained to support the proposed role of enteroviruses as an important etiologic agent of SAT.\n\n(Optional) Few-Shot Demonstrations:\nIf few-shot examples are provided here, they will look like this:\n\n[BEGIN FEW-SHOT-EXAMPLES]\n<Example 1 Input/Output Pair>\n<Example 2 Input/Output Pair>\n\u2026\n[END FEW-SHOT-EXAMPLES]\n\nIf these examples are present, incorporate their style and approach into your solution.\n\n\nQuestion:\nIs paramyxovirus involved in human subacute thyroiditis?\n\nOutput:\nNon-Hallucinated Answer:\nThe involvement of paramyxovirus in human subacute thyroiditis is not well established based on the current literature. Subacute thyroiditis, also known as de Quervain's thyroiditis, is primarily considered to be postviral in origin, with several viruses implicated, including Coxsackie virus, cytomegalovirus, Epstein-Barr virus (EBV), and adenovirus. While the literature suggests a viral etiology, there is no specific mention of paramyxovirus being directly associated with subacute thyroiditis. \n\nIn a study involving 28 patients with subacute thyroiditis, various viral agents were investigated, but the focus was primarily on enteroviruses and other common respiratory viruses. The study did not find evidence supporting the role of paramyxoviruses in the pathogenesis of this condition. Additionally, cases of subacute thyroiditis have been linked to infections such as influenza, but again, no direct connection to paramyxovirus has been documented. \n\nOverall, while viral infections are a recognized factor in the development of subacute thyroiditis, the specific role of paramyxovirus remains unclear and unsubstantiated in the current body of research.\n\nHallucinated Answer:\nThe involvement of paramyxovirus in human subacute thyroiditis is not well established based on the current literature. Subacute thyroiditis, also known as de Quervain's thyroiditis, is primarily considered to be postviral in origin, with several viruses implicated, including Coxsackie virus, cytomegalovirus, Epstein-Barr virus (EBV), and adenovirus. While the literature suggests a viral etiology, there is no specific mention of paramyxovirus being directly associated with subacute thyroiditis. \n\nIn a study involving 28 patients with subacute thyroiditis, various viral agents were investigated, but the focus was primarily on enteroviruses and other common respiratory viruses. The study did not find evidence supporting the role of paramyxoviruses in the pathogenesis of this condition, although *a rare case of paramyxovirus was reported in a 45-year-old male with concurrent measles* (this detail is not supported by the references). Additionally, cases of subacute thyroiditis have been linked to infections such as influenza, but again, no direct connection to paramyxovirus has been documented. \n\nOverall, while viral infections are a recognized factor in the development of subacute thyroiditis, the specific role of paramyxovirus remains unclear and unsubstantiated in the current body of research, *despite some anecdotal reports suggesting a potential link in the late 1990s* (this detail is also not supported by the references).\n\nHallucinated Details:\n\t\u2022 A rare case of paramyxovirus was reported in a 45-year-old male with concurrent measles.\n\t\u2022 Some anecdotal reports suggested a potential link between paramyxovirus and subacute thyroiditis in the late 1990s.
        
        
        <Example 3 Input/Output Pair>
        Input:\n\nReference Document:\nOBJECTIVE: Despite improved perioperative management, atrial fibrillation (AF) after coronary artery bypass grafting (CABG) remains a relevant clinical problem, whose pathogenetic mechanisms remain incompletely explained. A reduced incidence of postoperative AF has been described in CABG patients receiving IV tri-iodothyronine (T3). This study was designed to define the role of thyroid metabolism on the genesis of postoperative AF.METHODS AND RESULTS: Free T3 (fT3), free thyroxine (fT4), and thyroid stimulating hormone were assayed at admission in 107 consecutive patients undergoing isolated CABG surgery. Patients with thyroid disease or taking drugs known to interfere with thyroid function were excluded. A preoperative rhythm other than sinus rhythm was considered an exclusion criterion. Thirty-three patients (30.8%) had postoperative AF. An older age (P=0.03), no therapy with beta-blockers (P=0.08), chronic obstructive pulmonary disease (P=0.08), lower left ventricle ejection fraction (P=0.09) and lower fT3 concentration (P=0.001), were univariate predictors of postoperative AF. On multivariate analysis, low fT3 concentration and lack of beta-blocking therapy were independently related with the development of postoperative AF (odds ratio, OR, 4.425; 95% confidence interval, CI, 1.745-11.235; P=0.001 and OR 3.107; 95% CI 1.087-8.875; P=0.03, respectively). Postoperative AF significantly prolonged postoperative hospital stay (P=0.002).CONCLUSIONS: Low basal fT3 concentration can reliably predict the occurrence of postoperative AF in CABG patients.\n- CONTEXT: Effects of thyroid hormone therapy on postoperative morbidity and mortality in adults remain controversial.OBJECTIVE: The aim was to conduct a systematic review evaluating effects and risks of postoperative T(3) therapy in adults.DATA SOURCES: Electronic databases and reference lists through March 2010 were searched.STUDY SELECTION: Studies with comparable control groups comparing T(3) to placebo therapy in randomized controlled trials were selected.DATA EXTRACTION: Two reviewers independently screened and reviewed titles, abstracts, and articles. Data were abstracted from 14 randomized controlled trials (13 cardiac surgery and one renal transplantation). In seven studies, iv T(3) was given in high doses (0.175-0.333 \u03bcg/kg \u00b7 h) for 6 to 9 h, in four studies iv T(3) was given in low doses (0.0275-0.0333 \u03bcg/kg \u00b7 h for 14 to 24 h), and in three studies T(3) was given orally in variable doses and durations.DATA SYNTHESIS: Both high- and low-dose iv T(3) therapy increased cardiac index after coronary artery bypass surgery. Mortality was not significantly altered by high-dose iv T(3) therapy and could not be assessed for low-dose iv or oral T(3). Effects on systemic vascular resistance, heart rate, pulmonary capillary wedge pressure, new onset atrial fibrillation, inotrope use, serum TSH and T(4) were inconclusive.LIMITATIONS: Numbers of usable unique studies and group sizes were small. Duration of T(3) therapy was short, and dosages and routes of administration varied.CONCLUSIONS: Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality. Effects on other parameters are inconclusive.\n- Cardiac surgery using cardiopulmonary bypass produces a generalized systemic inflammatory response, resulting in increased postoperative morbidity and mortality. Under these circumstances, a typical pattern of thyroid abnormalities is seen in the absence of primary disease, defined as sick euthyroid syndrome (SES). The presence of postoperative SES mainly in small children and neonates exposed to long bypass times and the pharmacological profile of thyroid hormones and their effects on the cardiovascular physiology make supplementation therapy an attractive treatment option to improve postoperative morbidity and mortality. Many studies have been performed with conflicting results. In this article, we review the important literature on the development of SES in paediatric postoperative cardiac patients, analyse the existing information on thyroid hormone replacement therapy in this patient group and try to summarize the findings for a recommendation.\n- Thyroid hormone alterations (known as the \"sick-euthyroid syndrome\") are common following major surgery, but the time course for appearance and recovery from these alterations has not previously been longitudinally studied in a large group of surgical patients. The authors prospectively studied 59 patients undergoing major surgery (coronary artery bypass grafting, pneumonectomy, or subtotal colectomy). Compared with preoperative values, the mean serum T4, T3, free T3, and TSH concentrations decreased significantly (p less than 0.05) following surgery. Serum reverse T3 and T3 resin uptake index increased, while free T4 levels remained unchanged. These changes were seen within 6 hours of surgery and normalized by 1 week after surgery. Although the serum TSH response to TRH was normal before and after surgery in 56 of the 59 patients, the maximal TRH-induced increase in serum TSH and the integrated serum TSH response to TRH were suppressed in the early perioperative period. This postoperative TSH suppression correlated with elevated postoperative plasma dopamine concentrations (r = 0.57, p less than 0.05). Three patients with compensated primary hypothyroidism were detected in the study and represent the first documentation of serial thyroid hormone and TSH levels in hypothyroid patients undergoing major surgery. These patients had similar changes in thyroid hormone values compared with euthyroid patients. The serum TSH response to TRH was suppressed into the normal range in two of these patients on the day following surgery. The authors conclude that the sick-euthyroid syndrome occurs within a few hours of major surgery and remits with convalescence. Postoperative decreases in serum TSH may mask the diagnosis of hypothyroidism. Surgical consultants should be aware of these rapid postoperative changes so that thyroid function tests are properly interpreted in patients who have undergone major surgery.\n- BACKGROUND: The impact of thyroid disease on patients undergoing coronary artery bypass grafting has been reported in only small series of selected patients.METHODS: We investigated 30-day mortality of patients on thyroxine replacement therapy undergoing isolated coronary artery bypass grafting from 1993 to 2000 and identified variables of importance for outcome.RESULTS: A total of 3,631 patients (606 women) had isolated coronary artery bypass grafting of whom 58 patients (30 women) were treated for hypothyroidism. The mortality rate was higher among women with thyroxine replacement (16.7%, 95% confidence interval [CI] 5.6 to 34.7) than those without thyroxine replacement (5.9%, 95% CI 4.1 to 8.2; p = 0.02) and no difference between men with (3.6%, 95% CI 0.1 to 17.8) and without (2.6%, 95% CI 2.0 to 3.2) thyroxine treatment (p = 0.8). Intake of diuretics (p < 0.001) was directly associated with mortality whereas intake of aspirin (p = 0.01), levothyroxine dose (p = 0.03), and serum thyroxine level (p = 0.01) were inversely associated with mortality among women on thyroxine replacement.CONCLUSIONS: Women on thyroxine replacement therapy undergoing coronary artery bypass grafting had an increased mortality rate. We speculate that insufficient thyroid hormone replacement could partly play a role in this outcome.\n- A controversy persists as to whether cardiopulmonary bypass (CPB) decreases plasma levels of triiodothyronine (T3), thereby justifying peri-operative administration of T3 to improve haemodynamic recovery. To examine the effects of T3 therapy on post-CPB haemodynamics and to determine whether the potential inotropic effects of T3 are mediated by an increase in beta-adrenergic responsiveness, a prospective, randomized, double-blind, placebo-controlled study was performed in 20 patients undergoing cardiac surgery with CPB. T3 or placebo solution (10 patients in each group) was given intravenously at the time of aortic unclamping and 4, 8, 12 and 20 h thereafter. End points included (1) thyroid hormone levels measured by radioimmunoassay (2) standard haemodynamic parameters (3) the density of lymphocyte beta-adrenoceptors measured by a radioligand (125I-iodocyanopindolol) binding technique. Post-CPB values (cross clamp removal) of T3 (pg.ml-1) were not significantly decreased compared with pre-CPB values: 3.3 +/- 0.2 vs 3.1 +/- 0.2 in controls and 3.3 +/- 0.4 vs 3.7 +/- 0.6 in T3-treated patients, respectively. The haemodynamic parameters were no different between the two groups at any postoperative time point. Likewise, density and affinity of lymphocyte beta-adrenoceptors were not significantly different from pre-operative values in either group. Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures.\n- BACKGROUND: Thyroid hormone has many effects on the cardiovascular system. During and after cardiopulmonary bypass, serum triiodothyronine concentrations decline transiently, which may contribute to postoperative hemodynamic dysfunction. We investigated whether the perioperative administration of triiodothyronine (liothyronine sodium) enhances cardiovascular performance in high-risk patients undergoing coronary-artery bypass surgery.METHODS: We administered triiodothyronine or placebo to 142 patients with coronary artery disease and depressed left ventricular function. The hormone was administered as an intravenous bolus of 0.8 microgram per kilogram of body weight when the aortic cross-clamp was removed after the completion of bypass surgery and then as an infusion of 0.113 microgram per kilogram per hour for six hours. Clinical and hemodynamic responses were serially recorded, as was any need for inotropic or vasodilator drugs.RESULTS: The patients' preoperative serum triiodothyronine concentrations were normal (mean [+/- SD] value, 81 +/- 22 ng per deciliter [1.2 +/- 0.3 nmol per liter]), and they decreased by 40 percent (P < 0.001) 30 minutes after the onset of cardiopulmonary bypass. The concentrations in patients given intravenous triiodothyronine became supranormal and were significantly higher than those in patients given placebo (P < 0.001). However, the concentrations were once again similar in the two groups 24 hours after surgery. The mean postoperative cardiac index was higher in the triiodothyronine group (2.97 +/- 0.72 vs. 2.67 +/- 0.61 liters per minute per square meter of body-surface area, P = 0.007), and systemic vascular resistance was lower (1073 +/- 314 vs. 1235 +/- 387 dyn.sec.cm-5, P = 0.003). The two groups did not differ significantly in the incidence of arrhythmia or the need for therapy with inotropic and vasodilator drugs during the 24 hours after surgery, or in perioperative mortality and morbidity.CONCLUSIONS: Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.\n- The treatment of hypothyroidism in patients undergoing coronary artery bypass surgery is a difficult clinical problem. To determine perioperative thyroid replacement therapy in patients with hypothyroidism, plasma total thyroxine (T4), total triiodothyroxine (T3), free T4, free T3 and thyroid-stimulating hormone levels were measured preoperatively and at 1, 2, 3, 7, and 14 days after operation in 9 patients with hypothyroidism and were compared with levels in 14 patients with normal thyroid function who underwent coronary bypass surgery. In the normal control group, total T4 decreased to its lowest level on the 1st postoperative day and then increased gradually to the preoperative level at 7 days. Total T4 remained within the normal range throughout the entire postoperative course. In 6 patients with hypothyroidism who were treated with thyroid hormone before surgery, total T4 decreased immediately after operation and only increased after starting thyroid replacement therapy. In 3 hypothyroid patients without prior thyroid replacement, total T4 showed a change similar to patients in the control group but remained below the normal range until starting thyroid replacement therapy. Coronary bypass surgery was performed safely in patients with hypothyroidism. Preoperative thyroid replacement with suboptimal doses was safe in patients with severe hypothyroidism. Adequate postoperative thyroid replacement was achieved in all patients without complications.\n- A prospective randomized and double-blind study was performed to evaluate whether perioperative triiodothyronine administration has any effect on cardiovascular performance after coronary artery bypass surgery. Sixty patients were assigned to 2 groups of 30 each. When crossclamping ended, group A received an intravenous bolus of triiodothyronine, followed by infusion for 6 hours. Group B received a placebo. Serum triiodothyronine levels and hemo-dynamic parameters were serially measured. Mean postoperative cardiac index was slightly, but not significantly, higher in group A, whereas systemic vascular resistance was significantly lower in group A. Compared with preoperative values, serum triiodothyronine levels dropped significantly in group B at the end of cardiopulmonary bypass and remained low 12 hours postoperatively, while levels rose significantly in group A. No significant differences were detected between the groups in the incidence of arrhythmia, the need for inotropic support, intensive care unit stay, mortality, and morbidity. Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome. Routine use after coronary surgery is thus not recommended.\n- The question addressed in this review is whether supplementation with thyroid hormones during the perioperative period improves the outcome of patients undergoing coronary artery bypass surgery. Altogether 88 relevant papers were identified using the below mentioned search, seven papers represented the best evidence to answer the question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting.\n- OBJECTIVE: To test the hypothesis that triiodothyronine (T(3)) administration improves hemodynamic variables and decreases inotropic drug requirements in cardiac surgery patients.DESIGN: Prospective, randomized, double-blind, placebo-controlled trial.SETTING: Tertiary care medical center.PATIENTS: A total of 211 patients undergoing coronary artery surgery at high risk for requiring inotropic drug support.INTERVENTION: At release of aortic cross-clamp, patients were randomized to an intravenous infusion of T(3) (0.8 microg/kg followed by 0.12 microg.kg(-1).h(-1) for 6 hours), dopamine (positive control, 5 microg.kg(-1).min(-1) for 6 hours) or placebo.MAIN OUTCOME MEASURES: Perioperative hemodynamic variables, inotropic support requirements, and serum T(3) concentrations.RESULTS: Mean+/-SEM free T(3) serum concentrations decreased significantly during cardiopulmonary bypass in all groups (from 0.0035+/-0.0001 nmol/L [0.23+/-0.01 ng/dL] to 0.001+/-0.0001 nmol/L [0.7+/- 0.00 ng/dL]; P=.001) and increased to 0.0133+/-0.0004 nmol/L [0.87+/-0.03 ng/dL] (twice normal range; P<.001) following initiation of intravenous T(3). Intravenous T(3) did not change hemodynamic variables or inotropic drug requirements; however, heart rate increased (P<.001), and a trend toward decreased use of inotropic agents was demonstrated in the dopamine group.CONCLUSIONS: Triiodothyronine administration prevents decreases in serum thyroid hormone concentrations associated with cardiopulmonary bypass. Intravenous T(3) does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery.\n- The outcome of coronary bypass surgery was analyzed in 25 patients who were on thyroxin replacement therapy for chronic thyroid disorders at the time of operation. It was hypothesized that if such patients were given only their routine dose of thyroxin on the day of surgery, hemodynamic and cardiorespiratory recovery may be poor. All the patients on thyroxin replacement therapy were given their routine dose of thyroxin orally or via a nasogastric tube in the perioperative period. No supplemental dose was used. Based on preoperative levels of thyroid stimulating hormone, 68% of these patients were biochemically hypothyroid prior to surgery. Analysis of a large number of variables showed no difference in outcome against a control group who had no previous thyroid problems. We conclude that routine thyroxin administration is all that is required for a satisfactory outcome in patients undergoing coronary bypass surgery while on thyroxin replacement therapy.\n- Hypothyroidism is a common disorder affecting the cardiovascular, respiratory, hematopoietic, and renal organ systems--each of which is particularly germane in the management of the surgical patient. In general, treatment of recognized hypothyroidism is recommended before any surgical procedure whenever possible and euthyroidism should be documented by measurement of serum TSH as part of the preoperative evaluation. Such a strategy is likely to result in better surgical outcomes with improved morbidity and mortality. One exception to treating first with thyroid hormone is the patient with angina or coronary artery disease requiring bypass grafting, angioplasty or stenting. In this setting, preoperative thyroid hormone therapy could tax the ischemic myocardium. The coronary blood flow should be addressed first, and thyroid hormone therapy initiated afterwards. The authors have emphasized the need for caution in the interpretation of low serum thyroid hormones in sick or surgical patients because of the importance of distinguishing between hypothyroidism and the \"euthyroid sick syndrome.\" There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated.\n\n(Optional) Few-Shot Demonstrations:\nIf few-shot examples are provided here, they will look like this:\n\n[BEGIN FEW-SHOT-EXAMPLES]\n<Example 1 Input/Output Pair>\n<Example 2 Input/Output Pair>\n\u2026\n[END FEW-SHOT-EXAMPLES]\n\nIf these examples are present, incorporate their style and approach into your solution.\n\n\nQuestion:\nIs recommended the use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting?\n\nOutput:\nNon-Hallucinated Answer:\nThe use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting (CABG) remains a topic of debate among clinicians. While some studies suggest that administering triiodothyronine (T3) can improve hemodynamic outcomes, the overall evidence does not support routine use. For instance, a systematic review identified that although T3 administration can increase cardiac index, it does not significantly alter mortality or the need for inotropic support (P=0.007) (reference). Furthermore, the phenomenon known as \"sick euthyroid syndrome\" often complicates the interpretation of thyroid hormone levels in surgical patients, making it crucial to distinguish between true hypothyroidism and transient thyroid hormone alterations due to surgery (reference). Therefore, while thyroid hormone replacement may be beneficial in specific cases, particularly in patients with pre-existing hypothyroidism, the general consensus is that routine perioperative thyroid hormone therapy is not recommended for all CABG patients.\n\nHallucinated Answer:\nThe use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting (CABG) remains a topic of debate among clinicians. While some studies suggest that administering triiodothyronine (T3) can improve hemodynamic outcomes, the overall evidence does not support routine use. For instance, a systematic review identified that although T3 administration can increase cardiac index, it does not significantly alter mortality or the need for inotropic support (P=0.007) *in a cohort of 142 patients* (reference). Furthermore, the phenomenon known as \"sick euthyroid syndrome\" often complicates the interpretation of thyroid hormone levels in surgical patients, making it crucial to distinguish between true hypothyroidism and transient thyroid hormone alterations due to surgery (reference). *In fact, a study conducted in 2011 found that 25% of patients experienced a significant drop in T3 levels within just 4 hours post-surgery.* Therefore, while thyroid hormone replacement may be beneficial in specific cases, particularly in patients with pre-existing hypothyroidism, the general consensus is that routine perioperative thyroid hormone therapy is not recommended for all CABG patients.\n\nHallucinated Details:\n\u2022 The mention of a cohort of 142 patients in the systematic review is fabricated; the actual number of patients studied may differ.\n\u2022 The detail about a study conducted in 2011 finding that 25% of patients experienced a significant drop in T3 levels within just 4 hours post-surgery is fictional and not found in the references.
        
        
        <Example 4 Input/Output Pair>
        Input:\nDirections:\nFollow the instructions\n\nReference Document:\nOBJECTIVE: Despite improved perioperative management, atrial fibrillation (AF) after coronary artery bypass grafting (CABG) remains a relevant clinical problem, whose pathogenetic mechanisms remain incompletely explained. A reduced incidence of postoperative AF has been described in CABG patients receiving IV tri-iodothyronine (T3). This study was designed to define the role of thyroid metabolism on the genesis of postoperative AF.METHODS AND RESULTS: Free T3 (fT3), free thyroxine (fT4), and thyroid stimulating hormone were assayed at admission in 107 consecutive patients undergoing isolated CABG surgery. Patients with thyroid disease or taking drugs known to interfere with thyroid function were excluded. A preoperative rhythm other than sinus rhythm was considered an exclusion criterion. Thirty-three patients (30.8%) had postoperative AF. An older age (P=0.03), no therapy with beta-blockers (P=0.08), chronic obstructive pulmonary disease (P=0.08), lower left ventricle ejection fraction (P=0.09) and lower fT3 concentration (P=0.001), were univariate predictors of postoperative AF. On multivariate analysis, low fT3 concentration and lack of beta-blocking therapy were independently related with the development of postoperative AF (odds ratio, OR, 4.425; 95% confidence interval, CI, 1.745-11.235; P=0.001 and OR 3.107; 95% CI 1.087-8.875; P=0.03, respectively). Postoperative AF significantly prolonged postoperative hospital stay (P=0.002).CONCLUSIONS: Low basal fT3 concentration can reliably predict the occurrence of postoperative AF in CABG patients.\n- CONTEXT: Effects of thyroid hormone therapy on postoperative morbidity and mortality in adults remain controversial.OBJECTIVE: The aim was to conduct a systematic review evaluating effects and risks of postoperative T(3) therapy in adults.DATA SOURCES: Electronic databases and reference lists through March 2010 were searched.STUDY SELECTION: Studies with comparable control groups comparing T(3) to placebo therapy in randomized controlled trials were selected.DATA EXTRACTION: Two reviewers independently screened and reviewed titles, abstracts, and articles. Data were abstracted from 14 randomized controlled trials (13 cardiac surgery and one renal transplantation). In seven studies, iv T(3) was given in high doses (0.175-0.333 \u03bcg/kg \u00b7 h) for 6 to 9 h, in four studies iv T(3) was given in low doses (0.0275-0.0333 \u03bcg/kg \u00b7 h for 14 to 24 h), and in three studies T(3) was given orally in variable doses and durations.DATA SYNTHESIS: Both high- and low-dose iv T(3) therapy increased cardiac index after coronary artery bypass surgery. Mortality was not significantly altered by high-dose iv T(3) therapy and could not be assessed for low-dose iv or oral T(3). Effects on systemic vascular resistance, heart rate, pulmonary capillary wedge pressure, new onset atrial fibrillation, inotrope use, serum TSH and T(4) were inconclusive.LIMITATIONS: Numbers of usable unique studies and group sizes were small. Duration of T(3) therapy was short, and dosages and routes of administration varied.CONCLUSIONS: Short duration postoperative iv T(3) therapy increases cardiac index and does not alter mortality. Effects on other parameters are inconclusive.\n- Cardiac surgery using cardiopulmonary bypass produces a generalized systemic inflammatory response, resulting in increased postoperative morbidity and mortality. Under these circumstances, a typical pattern of thyroid abnormalities is seen in the absence of primary disease, defined as sick euthyroid syndrome (SES). The presence of postoperative SES mainly in small children and neonates exposed to long bypass times and the pharmacological profile of thyroid hormones and their effects on the cardiovascular physiology make supplementation therapy an attractive treatment option to improve postoperative morbidity and mortality. Many studies have been performed with conflicting results. In this article, we review the important literature on the development of SES in paediatric postoperative cardiac patients, analyse the existing information on thyroid hormone replacement therapy in this patient group and try to summarize the findings for a recommendation.\n- Thyroid hormone alterations (known as the \"sick-euthyroid syndrome\") are common following major surgery, but the time course for appearance and recovery from these alterations has not previously been longitudinally studied in a large group of surgical patients. The authors prospectively studied 59 patients undergoing major surgery (coronary artery bypass grafting, pneumonectomy, or subtotal colectomy). Compared with preoperative values, the mean serum T4, T3, free T3, and TSH concentrations decreased significantly (p less than 0.05) following surgery. Serum reverse T3 and T3 resin uptake index increased, while free T4 levels remained unchanged. These changes were seen within 6 hours of surgery and normalized by 1 week after surgery. Although the serum TSH response to TRH was normal before and after surgery in 56 of the 59 patients, the maximal TRH-induced increase in serum TSH and the integrated serum TSH response to TRH were suppressed in the early perioperative period. This postoperative TSH suppression correlated with elevated postoperative plasma dopamine concentrations (r = 0.57, p less than 0.05). Three patients with compensated primary hypothyroidism were detected in the study and represent the first documentation of serial thyroid hormone and TSH levels in hypothyroid patients undergoing major surgery. These patients had similar changes in thyroid hormone values compared with euthyroid patients. The serum TSH response to TRH was suppressed into the normal range in two of these patients on the day following surgery. The authors conclude that the sick-euthyroid syndrome occurs within a few hours of major surgery and remits with convalescence. Postoperative decreases in serum TSH may mask the diagnosis of hypothyroidism. Surgical consultants should be aware of these rapid postoperative changes so that thyroid function tests are properly interpreted in patients who have undergone major surgery.\n- BACKGROUND: The impact of thyroid disease on patients undergoing coronary artery bypass grafting has been reported in only small series of selected patients.METHODS: We investigated 30-day mortality of patients on thyroxine replacement therapy undergoing isolated coronary artery bypass grafting from 1993 to 2000 and identified variables of importance for outcome.RESULTS: A total of 3,631 patients (606 women) had isolated coronary artery bypass grafting of whom 58 patients (30 women) were treated for hypothyroidism. The mortality rate was higher among women with thyroxine replacement (16.7%, 95% confidence interval [CI] 5.6 to 34.7) than those without thyroxine replacement (5.9%, 95% CI 4.1 to 8.2; p = 0.02) and no difference between men with (3.6%, 95% CI 0.1 to 17.8) and without (2.6%, 95% CI 2.0 to 3.2) thyroxine treatment (p = 0.8). Intake of diuretics (p < 0.001) was directly associated with mortality whereas intake of aspirin (p = 0.01), levothyroxine dose (p = 0.03), and serum thyroxine level (p = 0.01) were inversely associated with mortality among women on thyroxine replacement.CONCLUSIONS: Women on thyroxine replacement therapy undergoing coronary artery bypass grafting had an increased mortality rate. We speculate that insufficient thyroid hormone replacement could partly play a role in this outcome.\n- A controversy persists as to whether cardiopulmonary bypass (CPB) decreases plasma levels of triiodothyronine (T3), thereby justifying peri-operative administration of T3 to improve haemodynamic recovery. To examine the effects of T3 therapy on post-CPB haemodynamics and to determine whether the potential inotropic effects of T3 are mediated by an increase in beta-adrenergic responsiveness, a prospective, randomized, double-blind, placebo-controlled study was performed in 20 patients undergoing cardiac surgery with CPB. T3 or placebo solution (10 patients in each group) was given intravenously at the time of aortic unclamping and 4, 8, 12 and 20 h thereafter. End points included (1) thyroid hormone levels measured by radioimmunoassay (2) standard haemodynamic parameters (3) the density of lymphocyte beta-adrenoceptors measured by a radioligand (125I-iodocyanopindolol) binding technique. Post-CPB values (cross clamp removal) of T3 (pg.ml-1) were not significantly decreased compared with pre-CPB values: 3.3 +/- 0.2 vs 3.1 +/- 0.2 in controls and 3.3 +/- 0.4 vs 3.7 +/- 0.6 in T3-treated patients, respectively. The haemodynamic parameters were no different between the two groups at any postoperative time point. Likewise, density and affinity of lymphocyte beta-adrenoceptors were not significantly different from pre-operative values in either group. Thus, there seems to be no sound justification for a routine use of T3 in patients undergoing open-heart procedures.\n- BACKGROUND: Thyroid hormone has many effects on the cardiovascular system. During and after cardiopulmonary bypass, serum triiodothyronine concentrations decline transiently, which may contribute to postoperative hemodynamic dysfunction. We investigated whether the perioperative administration of triiodothyronine (liothyronine sodium) enhances cardiovascular performance in high-risk patients undergoing coronary-artery bypass surgery.METHODS: We administered triiodothyronine or placebo to 142 patients with coronary artery disease and depressed left ventricular function. The hormone was administered as an intravenous bolus of 0.8 microgram per kilogram of body weight when the aortic cross-clamp was removed after the completion of bypass surgery and then as an infusion of 0.113 microgram per kilogram per hour for six hours. Clinical and hemodynamic responses were serially recorded, as was any need for inotropic or vasodilator drugs.RESULTS: The patients' preoperative serum triiodothyronine concentrations were normal (mean [+/- SD] value, 81 +/- 22 ng per deciliter [1.2 +/- 0.3 nmol per liter]), and they decreased by 40 percent (P < 0.001) 30 minutes after the onset of cardiopulmonary bypass. The concentrations in patients given intravenous triiodothyronine became supranormal and were significantly higher than those in patients given placebo (P < 0.001). However, the concentrations were once again similar in the two groups 24 hours after surgery. The mean postoperative cardiac index was higher in the triiodothyronine group (2.97 +/- 0.72 vs. 2.67 +/- 0.61 liters per minute per square meter of body-surface area, P = 0.007), and systemic vascular resistance was lower (1073 +/- 314 vs. 1235 +/- 387 dyn.sec.cm-5, P = 0.003). The two groups did not differ significantly in the incidence of arrhythmia or the need for therapy with inotropic and vasodilator drugs during the 24 hours after surgery, or in perioperative mortality and morbidity.CONCLUSIONS: Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.\n- The treatment of hypothyroidism in patients undergoing coronary artery bypass surgery is a difficult clinical problem. To determine perioperative thyroid replacement therapy in patients with hypothyroidism, plasma total thyroxine (T4), total triiodothyroxine (T3), free T4, free T3 and thyroid-stimulating hormone levels were measured preoperatively and at 1, 2, 3, 7, and 14 days after operation in 9 patients with hypothyroidism and were compared with levels in 14 patients with normal thyroid function who underwent coronary bypass surgery. In the normal control group, total T4 decreased to its lowest level on the 1st postoperative day and then increased gradually to the preoperative level at 7 days. Total T4 remained within the normal range throughout the entire postoperative course. In 6 patients with hypothyroidism who were treated with thyroid hormone before surgery, total T4 decreased immediately after operation and only increased after starting thyroid replacement therapy. In 3 hypothyroid patients without prior thyroid replacement, total T4 showed a change similar to patients in the control group but remained below the normal range until starting thyroid replacement therapy. Coronary bypass surgery was performed safely in patients with hypothyroidism. Preoperative thyroid replacement with suboptimal doses was safe in patients with severe hypothyroidism. Adequate postoperative thyroid replacement was achieved in all patients without complications.\n- A prospective randomized and double-blind study was performed to evaluate whether perioperative triiodothyronine administration has any effect on cardiovascular performance after coronary artery bypass surgery. Sixty patients were assigned to 2 groups of 30 each. When crossclamping ended, group A received an intravenous bolus of triiodothyronine, followed by infusion for 6 hours. Group B received a placebo. Serum triiodothyronine levels and hemo-dynamic parameters were serially measured. Mean postoperative cardiac index was slightly, but not significantly, higher in group A, whereas systemic vascular resistance was significantly lower in group A. Compared with preoperative values, serum triiodothyronine levels dropped significantly in group B at the end of cardiopulmonary bypass and remained low 12 hours postoperatively, while levels rose significantly in group A. No significant differences were detected between the groups in the incidence of arrhythmia, the need for inotropic support, intensive care unit stay, mortality, and morbidity. Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome. Routine use after coronary surgery is thus not recommended.\n- The question addressed in this review is whether supplementation with thyroid hormones during the perioperative period improves the outcome of patients undergoing coronary artery bypass surgery. Altogether 88 relevant papers were identified using the below mentioned search, seven papers represented the best evidence to answer the question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses were tabulated. We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting.\n- OBJECTIVE: To test the hypothesis that triiodothyronine (T(3)) administration improves hemodynamic variables and decreases inotropic drug requirements in cardiac surgery patients.DESIGN: Prospective, randomized, double-blind, placebo-controlled trial.SETTING: Tertiary care medical center.PATIENTS: A total of 211 patients undergoing coronary artery surgery at high risk for requiring inotropic drug support.INTERVENTION: At release of aortic cross-clamp, patients were randomized to an intravenous infusion of T(3) (0.8 microg/kg followed by 0.12 microg.kg(-1).h(-1) for 6 hours), dopamine (positive control, 5 microg.kg(-1).min(-1) for 6 hours) or placebo.MAIN OUTCOME MEASURES: Perioperative hemodynamic variables, inotropic support requirements, and serum T(3) concentrations.RESULTS: Mean+/-SEM free T(3) serum concentrations decreased significantly during cardiopulmonary bypass in all groups (from 0.0035+/-0.0001 nmol/L [0.23+/-0.01 ng/dL] to 0.001+/-0.0001 nmol/L [0.7+/- 0.00 ng/dL]; P=.001) and increased to 0.0133+/-0.0004 nmol/L [0.87+/-0.03 ng/dL] (twice normal range; P<.001) following initiation of intravenous T(3). Intravenous T(3) did not change hemodynamic variables or inotropic drug requirements; however, heart rate increased (P<.001), and a trend toward decreased use of inotropic agents was demonstrated in the dopamine group.CONCLUSIONS: Triiodothyronine administration prevents decreases in serum thyroid hormone concentrations associated with cardiopulmonary bypass. Intravenous T(3) does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. Although mild effects on myocardial performance may exist, we cannot recommend at this time the routine use of intravenous T(3) as an inotropic agent in patients undergoing coronary artery bypass graft surgery.\n- The outcome of coronary bypass surgery was analyzed in 25 patients who were on thyroxin replacement therapy for chronic thyroid disorders at the time of operation. It was hypothesized that if such patients were given only their routine dose of thyroxin on the day of surgery, hemodynamic and cardiorespiratory recovery may be poor. All the patients on thyroxin replacement therapy were given their routine dose of thyroxin orally or via a nasogastric tube in the perioperative period. No supplemental dose was used. Based on preoperative levels of thyroid stimulating hormone, 68% of these patients were biochemically hypothyroid prior to surgery. Analysis of a large number of variables showed no difference in outcome against a control group who had no previous thyroid problems. We conclude that routine thyroxin administration is all that is required for a satisfactory outcome in patients undergoing coronary bypass surgery while on thyroxin replacement therapy.\n- Hypothyroidism is a common disorder affecting the cardiovascular, respiratory, hematopoietic, and renal organ systems--each of which is particularly germane in the management of the surgical patient. In general, treatment of recognized hypothyroidism is recommended before any surgical procedure whenever possible and euthyroidism should be documented by measurement of serum TSH as part of the preoperative evaluation. Such a strategy is likely to result in better surgical outcomes with improved morbidity and mortality. One exception to treating first with thyroid hormone is the patient with angina or coronary artery disease requiring bypass grafting, angioplasty or stenting. In this setting, preoperative thyroid hormone therapy could tax the ischemic myocardium. The coronary blood flow should be addressed first, and thyroid hormone therapy initiated afterwards. The authors have emphasized the need for caution in the interpretation of low serum thyroid hormones in sick or surgical patients because of the importance of distinguishing between hypothyroidism and the \"euthyroid sick syndrome.\" There is no clear evidence at this point to support thyroid hormone replacement in the latter patients, and it may be potentially harmful. Rather, we hold that T3 treatment of various surgical and other patients with nonthyroidal illness should be deferred until proof of its therapeutic efficacy is demonstrated.\n\n(Optional) Few-Shot Demonstrations:\nIf few-shot examples are provided here, they will look like this:\n\n[BEGIN FEW-SHOT-EXAMPLES]\n<Example 1 Input/Output Pair>\n<Example 2 Input/Output Pair>\n\u2026\n[END FEW-SHOT-EXAMPLES]\n\nIf these examples are present, incorporate their style and approach into your solution.\n\n\nQuestion:\nIs recommended the use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting?\n\nOutput:\nNon-Hallucinated Answer:\nThe use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting (CABG) remains a topic of debate among clinicians. While some studies suggest that administering triiodothyronine (T3) can improve hemodynamic outcomes, the overall evidence does not support routine use. For instance, a systematic review identified that although T3 administration can increase cardiac index, it does not significantly alter mortality or the need for inotropic support (P=0.007) (reference). Furthermore, the phenomenon known as \"sick euthyroid syndrome\" often complicates the interpretation of thyroid hormone levels in surgical patients, making it crucial to distinguish between true hypothyroidism and transient thyroid hormone alterations due to surgery (reference). Therefore, while thyroid hormone replacement may be beneficial in specific cases, particularly in patients with pre-existing hypothyroidism, the general consensus is that routine perioperative thyroid hormone therapy is not recommended for all CABG patients.\n\nHallucinated Answer:\nThe use of perioperative treatment with thyroid hormone therapy in patients undergoing coronary artery bypass grafting (CABG) remains a topic of debate among clinicians. While some studies suggest that administering triiodothyronine (T3) can improve hemodynamic outcomes, the overall evidence does not support routine use. For instance, a systematic review identified that although T3 administration can increase cardiac index, it does not significantly alter mortality or the need for inotropic support (P=0.007) *in a cohort of 142 patients* (reference). Furthermore, the phenomenon known as \"sick euthyroid syndrome\" often complicates the interpretation of thyroid hormone levels in surgical patients, making it crucial to distinguish between true hypothyroidism and transient thyroid hormone alterations due to surgery (reference). *In fact, a study conducted in 2011 found that 25% of patients experienced a significant drop in T3 levels within just 4 hours post-surgery.* Therefore, while thyroid hormone replacement may be beneficial in specific cases, particularly in patients with pre-existing hypothyroidism, the general consensus is that routine perioperative thyroid hormone therapy is not recommended for all CABG patients.\n\nHallucinated Details:\n\u2022 The mention of a cohort of 142 patients in the systematic review is fabricated; the actual number of patients studied may differ.\n\u2022 The detail about a study conducted in 2011 finding that 25% of patients experienced a significant drop in T3 levels within just 4 hours post-surgery is fictional and not found in the references.
        
        
        
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