Enhancing mutation detection in multiple myeloma with an error-corrected ultra-sensitive NGS assay without plasma cell enrichment.

BACKGROUND: Risk stratification in multiple myeloma (MM) patients is crucial, and molecular genetic studies play a significant role in achieving this objective. Enrichment of plasma cells for next-generation sequencing (NGS) analysis has been employed to enhance detection sensitivity. However, these methods often come with limitations, such as high costs and low throughput. In this study, we explore the use of an error-corrected ultrasensitive NGS assay called positional indexing sequencing (PiSeq-MM). This assay can detect somatic mutations in MM patients without relying on plasma cell enrichment. METHOD: Diagnostic bone marrow aspirates (BMAs) and blood samples from 14 MM patients were used for exploratory and validation sets. RESULTS: PiSeq-MM successfully detected somatic mutations in all BMAs, outperforming conventional NGS using plasma cells. It also identified 38 low-frequency mutations that were missed by conventional NGS, enhancing detection sensitivity below the 5% analytical threshold. When tested in an actual clinical environment, plasma cell enrichment failed in most BMAs (14/16), but the PiSeq-MM enabled mutation detection in all BMAs. There was concordance between PiSeq-MM using BMAs and ctDNA analysis in paired blood samples. CONCLUSION: This research provides valuable insights into the genetic landscape of MM and highlights the advantages of error-corrected NGS for detecting low-frequency mutations. Although the current standard method for mutation analysis is plasma cell-enriched BMAs, total BMA or ctDNA testing with error correction is a viable alternative when plasma cell enrichment is not feasible.

Recovery of 240 metagenome-assembled genomes from coastal mariculture environments in South Korea.

The mariculture industry has seen a rapid expansion in recent years due to the increasing global demand for seafood. However, the industry faces challenges from climate change and increased pathogen pressure. Additionally, the chemicals used to enhance mariculture productivity are changing ocean ecosystems. This study analyzed 36 surface-water metagenomes from South Korean mussel, oyster, scallop, and shrimp farms to expand our understanding of aquaculture microbial genetic resources and the potential impacts of these anthropogenic inputs. We recovered 240 non-redundant species-level metagenome-assembled genomes (MAGs), comprising 224 bacteria, 13 archaea, and three eukaryotes. Most MAGs were assigned to Proteobacteria, Bacteroidota, and Actinobacteriota, with 40.7% remaining unclassified at the species level. Among the three eukaryotic MAGs, one was identified as a novel lineage of green algae, highlighting the uncharacterized genetic diversity in mariculture environments. Additionally, 22 prokaryotic MAGs harbored 26 antibiotic and metal resistance genes, with MAGs carrying beta-lactamases being particularly prevalent in most farms. The obtained microbiome data from mariculture environments can be utilized in future studies to foster healthy, sustainable mariculture practices.

Persistent Horner Syndrome Following Bilateral Endoscopic Thoracic Sympathotomy: A Case Report.

Horner syndrome, manifesting as ptosis and miosis, arises from disruptions within the oculosympathetic pathway. This syndrome is classified based on the lesion's location along the sympathetic nerve pathway into central, preganglionic, or postganglionic types. While endoscopic transthoracic sympathectomy, a surgical intervention for hyperhidrosis, is associated with several complications, including compensatory hyperhidrosis, Horner syndrome, and pneumothorax, these complications are notably rarer in sympathotomy procedures. Importantly, the incidence of Horner syndrome post-operatively is notably low, particularly in comparison to compensatory hyperhidrosis, with most cases being reversible and not necessitating further intervention. This report delineates a rare case of persistent Horner syndrome following a bilateral sympathotomy at the T3 and L3 levels, performed to alleviate symptoms of palmar and plantar hyperhidrosis. The discussion underscores the rarity of such a complication and explores the implications for surgical practice and patient counselling.

Effectiveness of Mechanical Bowel Preparation Before Robot-assisted Laparoscopic Gynecologic Surgery: a Randomized, Single-Blind, Controlled Trial.

OBJECTIVE: The objective of this randomized controlled trial is to compare the effect of bowel preparation using only oral polyethylene glycol electrolyte (PEG) solution vs. oral polyethylene glycol electrolyte solution (PEG) combined with mechanical sodium phosphate (NaP) enema on the surgical field visualization in patients undergoing robot-assisted laparoscopic gynecologic procedures. METHODS: Participants were randomized to either a single oral PEG solution or an oral PEG solution combined by mechanical NaP enema. The intraoperative visualization of the surgical field, the ease of manipulation of the bowels and overall difficulty level of the surgery were evaluated by the surgeon using a self-administered questionnaire. After the surgery, the patients completed a survey assessing postoperative gastrointestinal discomfort. RESULTS: 114 women were enrolled and randomized to oral PEG solution only group (n=48), and oral PEG plus mechanical NaP enema group (n=66). 42 women in oral PEG only group and 59 oral PEG plus NaP enema group completed the study. There was no difference in intraoperative visualization, or overall difficulty of the operation between the two groups, and bowel manipulation was easier in the oral PEG only group. Also, there was no difference in operating time between the groups. The patients' level of gastrointestinal discomfort after the surgery was not significantly different between the two groups. CONCLUSION: Routine use of mechanical NaP enema before robot-assisted laparoscopic gynecologic surgery is not recommended, because it has no additional benefit regarding intraoperative visualization or the surgical level of difficulty over oral bowel preparation methods.

The Impairment of Endothelial Autophagy Accelerates Renal Senescence by Ferroptosis and NLRP3 Inflammasome Signaling Pathways with the Disruption of Endothelial Barrier.

Autophagy is a cellular process that degrades damaged cytoplasmic components and regulates cell death. The homeostasis of endothelial cells (ECs) is crucial for the preservation of glomerular structure and function in aging. Here, we investigated the precise mechanisms of endothelial autophagy in renal aging. The genetic deletion of Atg7 in the ECs of Atg7flox/flox;Tie2-Cre mice accelerated aging-related glomerulopathy and tubulointerstitial fibrosis. The EC-specific Atg7 deletion in aging mice induced the detachment of EC with the disruption of glomerular basement membrane (GBM) assembly and increased podocyte loss resulting in microalbuminuria. A Transwell co-culture system of ECs and kidney organoids showed that the iron and oxidative stress induce the disruption of the endothelial barrier and increase vascular permeability, which was accelerated by the inhibition of autophagy. This resulted in the leakage of iron through the endothelial barrier into kidney organoids and increased oxidative stress, which led to ferroptotic cell death. The ferritin accumulation was increased in the kidneys of the EC-specific Atg7-deficient aging mice and upregulated the NLRP3 inflammasome signaling pathway. The pharmacologic inhibition of ferroptosis with liproxstatin-1 recovered the disrupted endothelial barrier and reversed the decreased expression of GPX4, as well as NLRP3 and IL-1ß, in endothelial autophagy-deficient aged mice, which attenuated aging-related renal injury including the apoptosis of renal cells, abnormal structures of GBM, and tubulointerstitial fibrosis. Our data showed that endothelial autophagy is essential for the maintenance of the endothelial barrier during renal aging and the impairment of endothelial autophagy accelerates renal senescence by ferroptosis and NLRP3 inflammasome signaling pathways. These processes may be attractive therapeutic targets to reduce cellular injury from renal aging.

Mass spectrometry (MS)-based metabolomics of plasma and urine in dry eye disease (DED)-induced rat model.

Dry eye disease (DED) is an ophthalmic disease associated with poor quality and quantity of tears, and the number of patients is steadily increasing. The aim of this study was to determine plasma and urine metabolites obtained from DED scopolamine animal model where dry eye conditions (DRY) are induced. It was also of interest to examine whether DED (scopolamine) rat model was exacerbated by treatment with benzalkonium chloride (BAC). Subsequently, plasma and urine metabolites were analyzed using liquid chromatography (LC) and gas chromatography (GC)-mass spectrometry (MS), respectively. Data demonstrated that DED indicators such as tear volume, tear breakup time (TBUT), and corneal damage in the DED groups (DRY and BAC group) differed from those of control (CON). Similar results were noted in inflammatory factors such as interleukin (IL-1ß), IL-6, and tumor necrosis factor (TNF)-α. In the partial least squares-discriminant analysis (PLS-DA) score plots, the three groups were distinctly separated from each other. In addition, the related metabolites were also associated with these distinct separations as evidenced by 9 and 14 in plasma and urine, respectively. Almost all of the selected metabolites were decreased in the DRY group compared to CON, and the BAC group was lower than the DRY. In plasma and urine, lysophosphatidylcholine/lysophosphatidylethanolamine, organic acids, amino acids, and sugars varied between three groups, and these metabolites were related to inflammation and oxidative stress. Data suggest that treatment with scopolamine with/without BAC-induced DED and affected the level of systemic metabolites involved in inflammation and oxidative stress.

Hydrophobic, ultraviolet radiation-shielding, and antioxidant functionalities of TEMPO-oxidized cellulose nanofibril film coated with modified lignin nanoparticles.

In this study, lignin nanoparticles (LN) and octadecylamine-modified LN (LN-ODA) were utilized as coating materials to enhance the hydrophobic, antioxidant, and ultraviolet radiation-shielding (UV-shielding) properties of a TEMPO-oxidized nanocellulose film (TOCNF). The water contact angle (WCA) of the TOCNF was approximately 53° and remained stable for 1 min, while the modified LN-ODA-coated TOCNF reached over 130° and maintained approximately 85° for an hour. Pure TOCNF exhibited low antioxidant properties (4.7 %), which were significantly enhanced in TOCNF-LN (81.6 %) and modified LN-ODA (10.3 % to 27.5 %). Modified LN-ODA-coated TOCNF exhibited antioxidant properties two to six times higher than those of pure TOCNF. Modified LN-ODA exhibited thermal degradation max (Tmax) at 421 °C, while pure LN showed the main degradation temperature at approximately Tmax 330 °C. The thermal stability of TOCNF-LN-ODA-coated materials remained consistent with that of pure TOCNF, while the crystallinity index of the sample showed a slight decrease due to the amorphous nature of the lignin structure. The tensile strength of TOCNF was approximately 114.1 MPa and decreased to 80.1, 51.3, and 30.3 MPa for LN-ODA coating at 5, 10, and 15 g/m2, respectively.

Myxoid lipoma in the perioral mandibular region: two case reports.

Lipomas are one of the most common mesenchymal tumors in the human body, exhibiting a heightened prevalence between the ages of 40 and 60 years. However, primary intraoral lipomas are rare. Myxoid lipoma, which is characterized by abundant mucoid components, is a particularly rare histological subtype of lipoma. This study presents two cases of myxoid lipoma that occurred outside the common age range for occurrence, one in the right submandibular area of a 67-year-old male and the other in the lower lip of a 3-year-old child. Through these case reports, the aim was to introduce myxoid lipoma, a rare subtype affecting facial areas, and provide a brief review to assist in the differential diagnosis, emphasizing the importance of pathological assessment. Even in age groups and anatomical locations not typically associated with lipomas, it is crucial to emphasize the necessity of careful evaluation.

Pharmacological inhibition of USP14 delays proteostasis-associated aging in a proteasome-dependent but foxo-independent manner.

Aging is often accompanied by a decline in proteostasis, manifested as an increased propensity for misfolded protein aggregates, which are prevented by protein quality control systems, such as the ubiquitin-proteasome system (UPS) and macroautophagy/autophagy. Although the role of the UPS and autophagy in slowing age-induced proteostasis decline has been elucidated, limited information is available on how these pathways can be activated in a collaborative manner to delay proteostasis-associated aging. Here, we show that activation of the UPS via the pharmacological inhibition of USP14 (ubiquitin specific peptidase 14) using IU1 improves proteostasis and autophagy decline caused by aging or proteostatic stress in Drosophila and human cells. Treatment with IU1 not only alleviated the aggregation of polyubiquitinated proteins in aging Drosophila flight muscles but also extended the fly lifespan with enhanced locomotive activity via simultaneous activation of the UPS and autophagy. Interestingly, the effect of this drug disappeared when proteasomal activity was inhibited, but was evident upon proteostasis disruption by foxo mutation. Overall, our findings shed light on potential strategies to efficiently ameliorate age-associated pathologies associated with perturbed proteostasis.Abbreviations: AAAs: amino acid analogs; foxo: forkhead box, sub-group O; IFMs: indirect flight muscles; UPS: ubiquitin-proteasome system; USP14: ubiquitin specific peptidase 14.

Oxysterol-binding protein-like 7 deficiency leads to ER stress-mediated apoptosis in podocytes and proteinuria.

Chronic kidney disease (CKD) is associated with renal lipid dysmetabolism among a variety of other pathways. We recently demonstrated that oxysterol-binding protein-like 7 (OSBPL7) modulates the expression and function of ATP-binding cassette subfamily A member 1 (ABCA1) in podocytes, a specialized type of cell essential for kidney filtration. Drugs that target OSBPL7 lead to improved renal outcomes in several experimental models of CKD. However, the role of OSBPL7 in podocyte injury remains unclear. Using mouse models and cellular assays, we investigated the influence of OSBPL7 deficiency on podocytes. We demonstrated that reduced renal OSBPL7 levels as observed in two different models of experimental CKD are linked to increased podocyte apoptosis, primarily mediated by heightened endoplasmic reticulum (ER) stress. Although as expected, the absence of OSBPL7 also resulted in lipid dysregulation (increased lipid droplets and triglycerides content), OSBPL7 deficiency-related lipid dysmetabolism did not contribute to podocyte injury. Similarly, we demonstrated that the decreased autophagic flux we observed in OSBPL7-deficient podocytes was not the mechanistic link between OSBPL7 deficiency and apoptosis. In a complementary zebrafish model, osbpl7 knockdown was sufficient to induce proteinuria and morphological damage to the glomerulus, underscoring its physiological relevance. Our study sheds new light on the mechanistic link between OSBPL7 deficiency and podocyte injury in glomerular diseases associated with CKD, and it strengthens the role of OSBPL7 as a novel therapeutic target.NEW & NOTEWORTHY OSBPL7 and ER stress comprise a central mechanism in glomerular injury. This study highlights a crucial link between OSBPL7 deficiency and ER stress in CKD. OSBPL7 deficiency causes ER stress, leading to podocyte apoptosis. There is a selective effect on lipid homeostasis in that OSBPL7 deficiency affects lipid homeostasis, altering cellular triglyceride but not cholesterol content. The interaction of ER stress and apoptosis supports that ER stress, not reduced autophagy, is the main driver of apoptosis in OSBPL7-deficient podocytes.

Transition from homelessness to becoming housed: A qualitative study.

AIM: To explore the transitional experiences of becoming housed from homelessness. DESIGN: A qualitative descriptive study. METHODS: Data were collected during 2017 and 2018 using a semi-structured interview method with 10 former homeless people who became housed at the time of the study. The grounded theory method was used to analyse qualitative data. RESULTS: 'Desire to keep a place to stretch out and lie down' was the basic social problem participants suffered during the transition from homeless to becoming housed. In addition, 'returning to the social world as a person living an ordinary life' was the basic social process that emerged as a core category. The process was divided into four phases: (1) being discarded from everyday life in the social world, (2) struggling to reconnect with society and (3) returning to the social world as a person living an ordinary life. CONCLUSION: The transition from homelessness to becoming housed is a significant experience for individuals that involves holistic changes. Community health nurses should consider their practical needs based on client views. IMPACT: What problem did the study address? This study explored the experiences of transitioning from homelessness to becoming housed among post-homeless individuals. What were the main findings? While moving from homelessness to becoming housed, homeless people experienced returning to the social world as a person living an ordinary life. They were also shown to go through the process of four stages. Where and on whom will the research have an impact? This study will contribute to suggesting a direction for self-reliance-based interventions among people who are homeless. Additionally, the findings will provide primary data to develop a program for social integration. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Clinical characteristics and otolith dysfunction in presbyvestibulopathy: A retrospective cross-sectional analysis.

Objective: The Bárány Society recently established diagnostic criteria for presbyvestibulopathy, an age-related bilateral vestibular impairments in older individuals. Drawing upon a cross-sectional database, this study delves into the demographic and clinical features of presbyvestibulopathy patients and investigates the implications of otolith dysfunction. Methods: The study retrospectively analyzed 1218 patients aged 60 years or older who visited the tertiary dizziness clinic in 2020, due to symptoms of dizziness or instability. By reviewing medical records, we gathered clinical information and laboratory vestibular test results, such as cervical and ocular vestibular evoked myogenic potentials, and subjective visual vertical. Results: Out of 1218 patients aged 60 and above who reported dizziness or unsteadiness, 33 patients (2.7 %, with an average age of 74.2 ± 9.2 years) were diagnosed with presbyvestibulopathy. Deficiencies in horizontal angular vestibulo-ocular reflex were found in caloric tests (75 %), video head impulse tests (51.7 %), and rotatory chair tests (47.8 %), respectively. Otolith dysfunction was also observed, as shown by abnormal ocular and cervical vestibular evoked myogenic potentials in 62.96 % and 51.85 % of patients, and abnormal subjective visual vertical in 45.8 % of the cases. Conclusions: Among elderly patients experiencing consistent dizziness or instability, the incidence of presbyvestibulopathy was approximately 2.7 % over one year. Alongside the abnormalities detected in the horizontal angular vestibulo-ocular reflex, significant changes were also noted in the ocular and cervical vestibular evoked myogenic potentials, as well as in the subjective visual vertical tests. As a result, it's vital to underscore the significance of both otolithic function and vestibulo-ocular reflex in the fundamental mechanisms of presbyvestibulopathy.

Gut microbiome and metabolome signatures in liver cirrhosis-related complications.

Background/Aims: Shifts in the gut microbiota and metabolites are interrelated with liver cirrhosis progression and complications. However, causal relationships have not been evaluated comprehensively. Here, we identified complication-dependent gut microbiota and metabolic signatures in patients with liver cirrhosis. Methods: Microbiome taxonomic profiling was performed on 194 stool samples (52 controls and 142 cirrhosis patients) via V3-V4 16S rRNA sequencing. Next, 51 samples (17 controls and 34 cirrhosis patients) were selected for fecal metabolite profiling via gas chromatography mass spectrometry and liquid chromatography coupled to time-of-flight-mass spectrometry. Correlation analyses were performed targeting the gut- microbiota, metabolites, clinical parameters, and presence of complications (varices, ascites, peritonitis, encephalopathy, hepatorenal syndrome, hepatocellular carcinoma, and deceased). Results: Veillonella bacteria, Ruminococcus gnavus, and Streptococcus pneumoniae are cirrhosis-related microbiotas compared with control group. Bacteroides ovatus, Clostridium symbiosum, Emergencia timonensis, Fusobacterium varium, and Hungatella_uc were associated with complications in the cirrhosis group. The areas under the receiver operating characteristic curve (AUROCs) for the diagnosis of cirrhosis, encephalopathy, hepatorenal syndrome, and deceased were 0.863, 0.733, 0.71, and 0.69, respectively. The AUROCs of mixed microbial species for the diagnosis of cirrhosis and complication were 0.808 and 0.847, respectively. According to the metabolic profile, 5 increased fecal metabolites in patients with cirrhosis were biomarkers (AUROC > 0.880) for the diagnosis of cirrhosis and complications. Clinical markers were significantly correlated with the gut microbiota and metabolites. Conclusion: Cirrhosis-dependent gut microbiota and metabolites present unique signatures that can be used as noninvasive biomarkers for the diagnosis of cirrhosis and its complications.

Three-month treatment outcome of medication-overuse headache according to classes of overused medications, use of acute medications, and preventive treatments.

Medication overuse headache (MOH) is a chronic headache disorder that results from excessive use of acutely symptomatic headache medications, leading to more frequent and severe headaches. This study aims to assess the 3-month treatment outcomes in MOH patients, focusing on the types and usage of overused medications, as well as preventive treatments. This prospective cross-sectional study analyzed the treatment outcomes of 309 MOH patients from April 2020 to March 2022. Patients were advised to discontinue overused medications immediately and offered preventive treatments based on clinical judgment. Data on headache characteristics, medication use, and impact on daily life were collected at baseline and 3 months. Results showed overall significant improvements in headache-related variables in patients completing the 3-month treatment follow-up. The median number of headache days per month decreased from 15 days at baseline to 8 days after 3 months (p < 0.001). Patients who overused multiple drug classes demonstrated increased disability levels (mean Headache Impact Test-6 score: 62 at baseline vs. 56 at 3 months, p < 0.01). Those who continued overusing medications reported more days of severe headache (mean 18 days at baseline vs. 14 days at 3 months, p < 0.05) and greater impact (mean Migraine Disability Assessment score: 35 at baseline vs. 28 after 3 months, p < 0.05) compared to the baseline. Differences in headache outcomes were evident across different preventive treatment groups, with generalized estimating equation analyses highlighting significant associations between clinical characteristics, overused medication classes, and preventive treatments. Most MOH clinical features significantly improved after 3 months of treatment. However, notable interactions were observed with certain clinical presentations, suggesting possible influences of overused medication classes, usage patterns, and preventive treatment types on MOH treatment outcomes. This study underscores the importance of individualized treatment strategies and the potential benefits of discontinuing overused medications.

Antibiotic Resistance in Acetic Acid Bacteria Originating from Vinegar.

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary and require safety evaluations, including antibiotic resistance, before use as a starter. In this research, we investigated the antibiotic resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter, against 10 different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study.

Phospholipase C beta 1 in the dentate gyrus gates fear memory formation through regulation of neuronal excitability.

Memory processes rely on a molecular signaling system that balances the interplay between positive and negative modulators. Recent research has focused on identifying memory-regulating genes and their mechanisms. Phospholipase C beta 1 (PLCß1), highly expressed in the hippocampus, reportedly serves as a convergence point for signal transduction through G protein-coupled receptors. However, the detailed role of PLCß1 in memory function has not been elucidated. Here, we demonstrate that PLCß1 in the dentate gyrus functions as a memory suppressor. We reveal that mice lacking PLCß1 in the dentate gyrus exhibit a heightened fear response and impaired memory extinction, and this excessive fear response is repressed by upregulation of PLCß1 through its overexpression or activation using a newly developed optogenetic system. Last, our results demonstrate that PLCß1 overexpression partially inhibits exaggerated fear response caused by traumatic experience. Together, PLCß1 is crucial in regulating contextual fear memory formation and potentially enhancing the resilience to trauma-related conditions.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Case report: Innovative treatment for one metastatic thyroid-like follicular carcinoma of the kidney with ATM and POLE mutations.

Thyroid-like follicular renal cell carcinoma (TLFRCC), also known as thyroid-like follicular carcinoma of the kidney or thyroid follicular carcinoma like renal tumor, is an exceedingly rare variant of renal cell carcinoma that has only recently been acknowledged. This neoplasm exhibits a distinct follicular morphology resembling that of the thyroid gland. Immunohistochemical analysis reveals positive expression of PAX8, Vimentin, and EMA, while thyroid-specific markers TG and TTF1 are consistently absent. Furthermore, there is a notable absence of any concurrent thyroid pathology on clinical evaluation. Previous reports have suggested that TLFRCC is an indolent, slow-growing malignancy with infrequent metastatic potential. In this report, we present a case of TLFRCC characterized by remarkable ossification and widespread metastasis, including multifocal pulmonary lesions, involvement of the abdominal wall, and infiltration into the psoas muscle. To our knowledge, this represents only the third documented instance of distant metastasis in thyroid follicular renal carcinoma. The current case demonstrates a therapeutic approach that combines radiotherapy with the utilization of toripalimab, a programmed cell death 1 (PD-1) receptor inhibitor, and pazopanib. This treatment regimen was tailored based on comprehensive genomic profiling, which identified mutations in the POLE (catalytic subunit of DNA polymerase epsilon) and ATM (ataxia-telangiectasia mutated) genes, both of which have been implicated in the pathogenesis of various malignant tumors. These findings represent a novel discovery, as such mutations have never been reported in association with TLFRCC. Thus far, this therapeutic approach has proven to be the most efficacious option for treating metastatic TLFRCC among previously reported, and it also marks the first mention of the potential benefits of radiotherapy in managing this particular subtype of renal cell carcinoma.