Implementing a context-augmented large language model to guide precision cancer medicine.

The rapid expansion of molecularly informed therapies in oncology, coupled with evolving regulatory FDA approvals, poses a challenge for oncologists seeking to integrate precision cancer medicine into patient care. Large Language Models (LLMs) have demonstrated potential for clinical applications, but their reliance on general knowledge limits their ability to provide up-to-date and niche treatment recommendations. To address this challenge, we developed a RAG-LLM workflow augmented with Molecular Oncology Almanac (MOAlmanac), a curated precision oncology knowledge resource, and evaluated this approach relative to alternative frameworks (i.

Personalized, disease-stage specific, rapid identification of immunosuppression in sepsis.

Introduction: Data overlapping of different biological conditions prevents personalized medical decision-making. For example, when the neutrophil percentages of surviving septic patients overlap with those of non-survivors, no individualized assessment is possible. To ameliorate this problem, an immunological method was explored in the context of sepsis.

Dual Immune Checkpoint Inhibition in Patients With Aggressive Thyroid Carcinoma: A Phase 2 Nonrandomized Clinical Trial.

Importance: Aggressive thyroid carcinoma, including radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC), are associated with significant morbidity and mortality and have limited therapeutic options. Distinct immune profiles have been identified in thyroid cancer subtypes suggesting they may be susceptible to immune checkpoint inhibition.

Objective: To evaluate the efficacy of anti-programmed cell death 1 nivolumab and anti-cytotoxic lymphocyte-associated protein 4 ipilimumab in patients with aggressive thyroid carcinoma.

An update on redifferentiation strategies for radioactive iodine-refractory differentiated thyroid carcinoma.

Purpose: Although most patients with differentiated thyroid carcinoma (DTC) have an excellent prognosis, a subset will experience radioactive iodine refractory (RAI-R) disease, associated with recurrence, distant metastases and worse prognosis. In recent years, redifferentiation has emerged as an attractive approach for patients with RAI-R DTC, a strategy to induce iodine uptake in RAI-R DTC tumor cells and ultimately prolong time to initiation of systemic therapy.

Methods: An overview and critical appraisal of the existing literature on redifferentiation will be presented in this review under the lens of the genotype-specific targeted therapy administered with redifferentiation intent.

A Phase I/II Trial of Sapanisertib in Advanced Anaplastic and Radioiodine Refractory Differentiated Thyroid Carcinoma.

Background: There are limited therapeutic options for patients with recurrent/metastatic anaplastic thyroid carcinoma (ATC) and radioiodine refractory (RAIR) differentiated thyroid carcinoma (DTC) refractory to multikinase inhibitors. This multicenter trial evaluated sapanisertib, a next-generation oral kinase inhibitor of mTOR complexes 1/2, in ATC and RAIR DTC.

Methods: A safety run-in phase I was followed by nonrandomized phase II trial in ATC, with an exploratory cohort in RAIR DTC.

STR mutations on chromosome 15q cause thyrotropin resistance by activating a primate-specific enhancer of MIR7-2/MIR1179.

Thyrotropin (TSH) is the master regulator of thyroid gland growth and function. Resistance to TSH (RTSH) describes conditions with reduced sensitivity to TSH. Dominantly inherited RTSH has been linked to a locus on chromosome 15q, but its genetic basis has remained elusive.

Nonoperative, Active Surveillance of Larger Malignant and Suspicious Thyroid Nodules.

Context: Active surveillance for papillary thyroid cancer (PTC) meeting criteria for surgical resection is uncommon. Which patients may prove reasonable candidates for this approach is not well defined.

Objective: This work aimed to examine the feasibility and safety of active surveillance for patients with known or suspected intrathyroidal PTC up to 4 cm in diameter.

Additional Oncogenic Alterations in RAS-Driven Differentiated Thyroid Cancers Associate with Worse Clinicopathologic Outcomes.

Purpose: RAS mutations occur across the spectrum of thyroid neoplasms, and more tools are needed for better prognostication. The objective of this study was to evaluate how additional genetic events affecting key genes modify prognosis in patients with RAS-mutant thyroid cancers, and specifically differentiated thyroid cancers (DTC).

Experimental Design: We performed a clinical-genomic analysis of consecutive patients with DTC, poorly differentiated (PDTC), or anaplastic thyroid cancer (ATC) between January 2014 and December 2021, in whom a custom-targeted next-generation sequencing assay was performed.

Papillary Thyroid Carcinomas with Tall Cell Features: An Intermediate Entity Between Classic and Tall Cell Subtypes.

While the diagnosis of papillary thyroid carcinomas (PTCs) with tall cell features (PTCtcf) is often made for carcinomas with histological features intermediate between classic and tall cell subtypes of PTC (tcPTC), its comparative signature to that of either tcPTC or classic PTC is less clear. The objective of this study was to perform an integrative clinicopathologic and genomic analysis elucidating the spectrum of tcPTC, PTCtcf, and classic PTC. We analyzed all consecutive patients with tcPTC and PTCtcf evaluated at a tertiary academic referral center between 2005 and 2020, as well as a comparative cohort of classic PTC, in a retrospective observational cohort analysis.

Clinical experience following implementation of routine SPECT-CT imaging following 131-iodine administration for thyroid cancer.

Background: Planar scintigraphy has long been indicated in patients receiving I-131 therapy for thyroid cancer to determine the anatomic location of metastases. We studied our experience upon implementing additional single-photon emission (SPECT)-CT scanning in these patients.

Method: We performed a retrospective study of consecutive adult patients with newly diagnosed thyroid cancer treated with I-131 between 2011 and 2017.

Thyroid Nodule Shape Independently Predicts Risk of Malignancy.

Context: Predictive models of thyroid nodule cancer risk are presently based upon nodule composition, echogenicity, margins, and the presence of microcalcifications. Nodule shape has shown promise to be an additive factor helping determine the need for nodule biopsy.

Objective: We sought to determine if calculation of a nodule's spherical shape independently associates with cancer risk.

Point of Care Measurement of Body Mass Index and Thyroid Nodule Malignancy Risk Assessment.

Background: Large scale epidemiology studies have suggested obesity may increase the risk of thyroid cancer, though no prospective analyses using real-world measurement of BMI at a time proximate to initial thyroid nodule evaluation have been performed.

Methods: We performed a prospective, cohort analysis over 3 years of consecutive patients presenting for thyroid nodule evaluation. We measured BMI proximate to the time of initial evaluation and correlated this with the final diagnosis of benign or malignant disease.

Daily Behaviors, Worries and Emotions in Children and Adolescents with ADHD and Learning Difficulties during the COVID-19 Pandemic.

The aim of the present study was to investigate the effects of the coronavirus crisis on behavioral and emotional parameters in children and adolescents with ADHD and Learning Difficulties. A total of 101 children, 5-18 years old, were included in the study, 63 (44 boys) of which were diagnosed with ADHD and learning difficulties (ADHD/LD) and 38 were healthy children (19 boys). The CRISIS questionnaire for parents/caregivers was used.

Oncogenic Mutations in PI3K/AKT/mTOR Pathway Effectors Associate with Worse Prognosis in -Driven Papillary Thyroid Cancer Patients.

Purpose: The extent to which routine genomic sequencing can identify relevant secondary genomic alterations among -mutant papillary thyroid carcinoma (PTC) is unknown. Such markers would prove highly valuable for prognostic purposes.

Experimental Design: We reviewed clinicopathologic data of 225 patients with -mutant PTC and integrated them with genomic data derived from targeted next-generation sequencing (NGS) on tumor specimens.

The Role of Thyroid in Renovascular Function: Independent Association of Serum TSH With Renal Plasma Flow.

Context: There are well-established interactions between the thyroid and the kidney. Thyroid hypofunction is associated with reduced renal plasma flow (RPF), and hypothyroidism is highly prevalent in chronic kidney disease; however, less is known about the thyroid-kidney axis in the euthyroid state.

Objective: This work aimed to study the association of thyroid function with renovascular parameters in a well-phenotyped cohort of euthyroid normotensive and hypertensive individuals.

Resistance to Thyroid Hormone Beta: A Focused Review.

Resistance to thyroid hormone (RTH) is a clinical syndrome defined by impaired sensitivity to thyroid hormone (TH) and its more common form is caused by mutations in the gene, termed RTHβ. The characteristic biochemical profile is that of elevated serum TH levels in absence of thyrotropin suppression. Although most individuals are considered clinically euthyroid, there is variability in phenotypic manifestation among individuals harboring different mutations and among tissue types in the same individual due in part to differential expression of the mutant TRβ protein.

Prenatal Treatment of Thyroid Hormone Cell Membrane Transport Defect Caused by Gene Mutation.

Mutations of the thyroid hormone (TH)-specific cell membrane transporter, (), produce an X-chromosome-linked syndrome of TH deficiency in the brain and excess in peripheral tissues. The clinical consequences include brain hypothyroidism causing severe psychoneuromotor abnormalities (no speech, truncal hypotonia, and spastic quadriplegia) and hypermetabolism (poor weight gain, tachycardia, and increased metabolism, associated with high serum levels of the active TH, T3). Treatment in infancy and childhood with TH analogues that reduce serum triiodothyronine (T3) corrects hypermetabolism, but has no effect on the psychoneuromotor deficits.

Nonautoimmune Hyperthyroidism Caused by a Somatic Mosaic Mutation Involving Part of the Thyroid Gland.

Nonautoimmune hyperthyroidism caused by activating mutations in the gene is a rare condition. In this study, we report a five-year-old girl diagnosed with nonautoimmune hyperthyroidism and tall stature harboring a somatic mosaic gain-of-function mutation in the gene (NM_080425.3: c.

Characteristics of clear cell renal cell carcinoma metastases to the thyroid gland: A systematic review.

Background: Thyroid gland is an uncommon site for metastases from clear cell renal cell carcinoma (CCRCC) and literature is scarce. Due to the variable and often long lag time before development of metastases in patients with CCRCC, thyroid nodules may be misdiagnosed initially as benign. This systematic review aims at a better understanding of the nature of these metastases.

Human Genetics of Thyroid Hormone Receptor Beta: Resistance to Thyroid Hormone Beta (RTHβ).

Resistance to thyroid hormone beta (RTHβ) is a syndrome characterized by reduced responsiveness of peripheral tissues to thyroid hormone (TH). Affected individuals have consistently high TH levels and non-suppressed thyrotropin in the absence of acute illness, drugs, or alterations in TH binding proteins. Depending on the tissue, features of TH excess and deficiency may coexist, although most individuals have a euthyroid, normal metabolic state at the expense of high TH levels.

Prenatal Diagnosis of Resistance to Thyroid Hormone and Its Clinical Implications.

Context: Resistance to thyroid hormone-β (RTH-β) is an autosomal dominant disorder characterized by reduced sensitivity of target tissues to thyroid hormones (THs). Individuals with RTH-β have high TH levels usually due to mutations in the TH receptor-β (THRB) gene. The management of RTH-β during pregnancy is challenging, as wild-type (WT) fetuses born to RTH-β mothers have low birth weight and suppressed postnatal thyroid-stimulating hormone (TSH), due to intrauterine exposure to excess TH.

Management of hereditary medullary thyroid carcinoma.

Hereditary medullary thyroid carcinoma (MTC) represents up to one-third of MTC cases and includes multiple endocrine neoplasia syndrome type 2A (and its variant familial MTC) and 2B. The aim of this paper is to provide an overview of the disease focusing on the management of hereditary MTC patients, who have already developed tumor, as well as discuss the recommended approach for asymptomatic family members carrying the same mutation. A PubMed search was performed to review recent literature on diagnosis, genetic testing, and surgical and medical management of hereditary MTC.