An In Vitro Hybrid Biocatalytic System Enabled by a Combination of Surface-Displayed, Purified, and Cell-Free Expressed Enzymes.

Enzymatic cascades have become a green and sustainable approach for the synthesis of valuable chemicals and pharmaceuticals. Using sequential enzymes to construct a multienzyme complex is an effective way to enhance the overall performance of biosynthetic routes. Here we report the design of an efficient in vitro hybrid biocatalytic system by assembling three enzymes that can convert styrene to (S)-1-phenyl-1,2-ethanediol. Specifically, we prepared the three enzymes in different ways, which were cell surface-displayed, purified, and cell-free expressed. To assemble them, we fused two orthogonal peptide-protein pairs (i.e., SpyTag/SpyCatcher and SnoopTag/SnoopCatcher) to the three enzymes, allowing their spatial organization by covalent assembly. By doing this, we constructed a multienzyme complex, which could enhance the production of (S)-1-phenyl-1,2-ethanediol by 3 times compared to the free-floating enzyme system without assembly. After optimization of the reaction system, the final product yield reached 234.6 µM with a substrate conversion rate of 46.9% (based on 0.5 mM styrene). Taken together, our strategy integrates the merits of advanced biochemical engineering techniques, including cellular surface display, spatial enzyme organization, and cell-free expression, which offers a new solution for chemical biosynthesis by enzymatic cascade biotransformation. We, therefore, anticipate that our approach will hold great potential for designing and constructing highly efficient systems to synthesize chemicals of agricultural, industrial, and pharmaceutical significance.

Cell-free biosynthesis and engineering of ribosomally synthesized lanthipeptides.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a major class of natural products with diverse chemical structures and potent biological activities. A vast majority of RiPP gene clusters remain unexplored in microbial genomes, which is partially due to the lack of rapid and efficient heterologous expression systems for RiPP characterization and biosynthesis. Here, we report a unified biocatalysis (UniBioCat) system based on cell-free gene expression for rapid biosynthesis and engineering of RiPPs. We demonstrate UniBioCat by reconstituting a full biosynthetic pathway for de novo biosynthesis of salivaricin B, a lanthipeptide RiPP. Next, we delete several protease/peptidase genes from the source strain to enhance the performance of UniBioCat, which then can synthesize and screen salivaricin B variants with enhanced antimicrobial activity. Finally, we show that UniBioCat is generalizable by synthesizing and evaluating the bioactivity of ten uncharacterized lanthipeptides. We expect UniBioCat to accelerate the discovery, characterization, and synthesis of RiPPs.

Testing region selection and prognostic analysis of MLH1 promoter methylation in colorectal cancer in China.

Background: MLH1 promoter methylation analysis is recommended in screening for Lynch syndrome (LS) in patients with MLH1-deficient colorectal cancer (CRC). The study aims to identify specific methylation regions in the MLH1 promoter and to evaluate the clinicopathologic characteristics of and prognosis for patients with MLH1 methylation. Methods: A total of 580 CRC cases were included. The DNA mismatch repair (MMR) protein expression was assessed by using immunohistochemistry (IHC). The methylation status of the Regions A, B, C, D, and E in the MLH1 promoter was tested by using bisulfite sequencing PCR. The specificities of the five regions were calculated. Associations between MLH1 methylation and clinicopathologic characteristics were evaluated. Kaplan-Meier analyses for overall survival (OS) were carried out. Results: In 580 CRC cases, the specificities of the methylation test in Regions D and E were both 97.8%. In the MLH1-deficient CRCs, the frequencies of MLH1 methylation and BRAFV600E mutation were 52.6% and 14.6%, respectively; BRAFV600E mutation occurred in 27.7% of patients with MLH1-methylated CRC. In the MMR-deficient patients, compared with MLH1 unmethylation, MLH1 methylation was more common in patients who were aged ≥50 years, female, had no family history of LS-related tumors, and had tumors located at the right colon. In the MMR-deficient patients, the MLH1-methylated cases had lower OS rates than the unmethylated cases with a family history of LS-related tumors (P = 0.047). Conclusions: Regions D and E in the MLH1 promoter are recommended for determining the MLH1 methylation status in screening for LS in MLH1-deficient CRC. In MMR-deficient patients, the MLH1-methylated cases had a worse OS than the unmethylated cases with a family history of LS-related cancer.

Prognosis and immunotherapy efficacy in dMMR&MSS colorectal cancer patients and an MSI status predicting model.

The inconsistency between mismatch repair (MMR) protein immunohistochemistry (IHC) and microsatellite instability PCR (MSI-PCR) methods has been widely reported. We aim to investigate the prognosis and the effect of immunotherapy in dMMR by IHC but MSS by MSI-PCR (dMMR&MSS) colorectal cancer (CRC) patients. A microsatellite instability (MSI) predicting model was established to help find dMMR&MSS patients. MMR and MSI states were detected by the IHC and MSI-PCR in 1622 CRC patients (ZS6Y-1 cohort). Logistic regression analysis was used to screen clinical features to construct an MSI-predicting nomogram. We propose a new nomogram-based assay to find patients with dMMR&MSS, in which the MSI-PCR assay only detects dMMR patients with MSS predictive results. We applied the new strategy to a random cohort of 248 CRC patients (ZS6Y-2 cohort). The consistency of MMR IHC and MSI-PCR in the ZS6Y-1 cohort was 95.7% (1553/1622). Both pMMR&MSS and dMMR&MSS groups experienced significantly shorter overall survival (OS) than those in dMMR by IHC and MSI-H by MSI-PCR (dMMR&MSI-H) group (hazard ratio [HR] = 2.429, 95% confidence interval [CI]: 1.89-3.116, p < .01; HR = 21.96, 95% CI: 7.24-66.61, p < .01). The dMMR&MSS group experienced shorter OS than the pMMR&MSS group, but the difference did not reach significance (log rank test, p = .0686). In the immunotherapy group, the progression-free survival of dMMR&MSS patients was significantly shorter than that of dMMR&MSI-H patients (HR = 13.83, 95% CI: 1.508-126.8, p < .05). The ZS6Y-MSI-Pre nomogram (C-index = 0.816, 95% CI: 0.792-0.841, already online) found 66% (2/3) dMMR&MSS patients in the ZS6Y-2 cohort. There are significant differences in OS and immunotherapy effect between dMMR&MSI-H and dMMR&MSS patients. Our prediction model provides an economical way to screen dMMR&MSS patients.

Reevaluating the splice-altering variant in TECTA as a cause of nonsyndromic hearing loss DFNA8/12 by functional analysis of RNA.

PURPOSE: The aim of this study was to determine the genetic cause of early onset autosomal dominant hearing loss segregating in five-generation kindred of Chinese descent and provide preimplantation genetic testing (PGT)for them. METHODS: Clinical examination, pedigree analysis and exome sequencing were carried out on the family. Minigene-based splicing analysis, in vivo RNA analysis and protein structure prediction by molecular modeling were conducted on the candidate variant. PGT for the causative variation and chromosome aneuploidis based on SNP analysis has been used for avoidance of hearing loss in this family. RESULTS: All the affected individuals presented with moderate down-sloping hearing loss and whole-exome sequencing identified a novel splice-site variant c.5383+6T>A in the tested subjects within the TECTA locus. Genotyping of all the 32 family members confirmed segregation of this variant and the hearing loss phenotype in the extended family. Functional analysis of RNA and molecular modeling indicates that c.5383+6T>A is a pathogenic splice-site variant and should be considered as genetic cause of the hearing loss. Furthermore, a successful singleton pregnancy with no variation in TECTA c.5383+6 was established and a healthy male child was born by PGT. CONCLUSION: We have identified a novel variant c.5383+6T>A in TECTA ZA-ZP inter-domain, which could be attributable to the early-onset autosomal dominant hearing loss. The implications of our study are valuable in elucidating the disrupted RNA splicing and uncovering the genetic cause of hearing loss with TECTA pathogenic variants, as well as providing reproductive approaches to healthy offspring.

Effect of Al/Ni Ratio on the Microstructure and Properties of Nickel-Aluminum Bronze Alloys.

To study the effect of aluminum and nickel elements on the microstructures and properties of the nickel-aluminum bronze (NAB) alloy, four kinds of alloys with different compositions, ZCuAl7-7-4-2, ZCuAl8-6-4-2, ZCuAl9-5-4-2, and ZCuAl10-4-4-2, are prepared by vacuum-melting technology. The effects of different Al/Ni ratios on the microstructures of NAB are investigated using a metalloscope, scanning electron microscopy, transmission electron microscopy, and XPS analysis. The mechanical property is evaluated with microhardness testing and tensile mechanical testing. The corrosion resistance is evaluated using mass-loss testing, electrochemical testing, and corrosion-product characterization. The results show that with the increase of the Al/Ni ratio, the content of precipitated phases increases, while ß' and hard κ, which have a different morphology, appear. As the Al/Ni ratio rises from 1 to 2.5, the hardness increases from 104 HV to 202 HV, and the tensile strength increases by 394 MPa from 356 MPa to 751 MPa, but the elongation decreases substantially from 50.50% to 11.00%. The best corrosion resistance is shown on ZCuAl7-7-4-2, with a corrosion rate of 0.00267 mm/a after 30 d of static immersion corrosion in 3.5 wt.% NaCl solution. Through electrochemical testing and corrosion-product characterization, it is found that ZCuAl7-7-4-2 has the largest polarization resistance Rp, and the selective corrosion of the surface is mild.

Successful endotracheal intervention for primary tracheal acinic cell carcinoma: A case report and literature review.

INTRODUCTION: Primary tracheal acinic cell carcinoma (ACC) is an exceptionally rare malignancy, posing challenges in understanding its clinical behavior and optimal management. Surgical resection has traditionally been the primary treatment modality, but we present a compelling case of tracheal ACC managed with endotracheal intervention, challenging conventional approaches. PATIENT CONCERNS: A 53-year-old woman presented with shortness of breath, cough, and hemoptysis. Enhanced computed tomography revealed an obstructive tracheal lesion, leading to her referral for further assessment. DIAGNOSIS: Microscopic evaluation, immunohistochemistry, and clinical assessments confirmed primary tracheal ACC, an exceedingly rare condition with limited clinical insights. INTERVENTIONS: We utilized rigid bronchoscopy to perform endotracheal intervention, successfully resecting the tumor and restoring tracheal patency. Postoperatively, the patient received no radiotherapy or chemotherapy. OUTCOMES: The patient achieved complete recovery, with 24-month follow-up examinations indicating no recurrence or metastatic disease. Only minimal scar tissue remained at the resection site. CONCLUSION: This case demonstrates the potential of endotracheal intervention as a curative approach for primary tracheal ACC, minimizing invasiveness and preserving tracheal function. Collaborative research efforts and extensive case reporting are crucial for advancing our understanding of this rare malignancy and optimizing treatment strategies for improved patient outcomes.

Prenatally Diagnosed Congenital Oral Teratoma Successfully Treated in a Neonate.

Teratomas are congenital malformations that rarely occur in the oral cavity. In the case reported here, fetal magnetic resonance imaging performed at 30 weeks of gestation informed the decision-making of the multidisciplinary management team, who closely followed the pregnancy until the scheduled cesarean delivery at 38 weeks of gestation. After delivery, tracheal intubation was performed to ensure airway patency, and tumor resection was scheduled immediately after ruling out contraindications to surgery based on preoperative examinations, allowing for safe excising of the tumor. Postoperative follow-up at 3 months showed no abnormalities.

CXCL16 promotes tumor metastasis by regulating angiogenesis in the tumor micro-environment of BRAF V600E mutant colorectal cancer.

Patients of colorectal cancer (CRC) with BRAF V600E mutation obtain poor prognosis. This study aimed to explore the role and mechanism of BRAF V600E mutation in angiogenesis of tumor micro-environment (TME). It has been reported that CXCL16 expression in TME is closely related to BRAF mutation. Clinicopathological features of CRC with BRAF V600E mutant or wild type were collected in this study. Immunohistochemistry (IHC) assays were conducted to test the expressions of vascular endothelial growth factor (VEGF), CD31 and CXCL16. ROC curve was used to determine the optimal cut off values of CXCL16. A total of 680 patients including 141 BRAF V600E type and 679 wild type were included. BRAF V600E mutant tumors were presented with significant worse clinicopathological features and a shorter overall survival (OS) than wild-type. Besides, chemokines CXCL16 was up-regulated in BRAF V600E mutant tissues and was associated with poorer prognosis. In addition, VEGF levels and vascular endothelial cell density was significantly increased in BRAF mutation. At last, CXCL16 was positively correlated with VEGF expression and vascular endothelial cell density. In conclusion, BRAF V600E mutations may promote metastasis of CRC by regulating CXCL16 expression and promoting angiogenesis in the TME.

A Retrospective Analysis of Robertsonian Translocations from a Single Center in China.

Robertsonian translocations (ROBs) are the most common structural chromosomal abnormalities in the general population, with an estimated incidence rate of 1/1000 births. In this study, we retrospectively analyzed the cases of ROBs from September 2015 to August 2022 and totally identified ROB carriers from 84,569 specimens karyotyped in a single accredited laboratory in China, including 189 cases of balanced ROBs and 3 of mosaic ROBs. Microsoft Excel and descriptive statistics were used to record and analyze the collected data. The male/female ratio of ROBs is 1/1.29, with der(13;14) and der(14;21) being the main karyotypes. Among the 192 patients, 7 were lost to follow-up, 82 had given birth, and 103 were childless (such as miscarriage, fetal chromosomal abnormalities, in vitro fertilization (IVF) failure, or divorce). A total of 44 amniocenteses were performed in 42 couples; ROB cases with natural pregnancies showed that the normal karyotype and balanced ROBs of fetal accounted for 66.67% (16/24), while the results of assisted pregnancies showed 90.00% (18/20). This study represents the largest collections of ROBs in Jiangxi population and reminder that the ROB carriers can achieve the ideal outcome for pregnancy with the appropriate genetic guidance and assisted reproductive technologies (ART).

Head-to-head comparative study: evaluating three panels for MSI-PCR testing in patients with colorectal and gastric cancer.

AIMS: Due to the lack of large clinical cohorts in the Chinese populations with colorectal cancer (CRC) and gastric cancer (GC), there is no consensus among the preferred panel for microsatellite instability (MSI)-PCR testing. This study aims to evaluate a more appropriate panel. METHODS: We tested the MSI status of 2572 patients with CRC and GC using the NCI panel and 2 mononucleotide panels (5 and 6 mononucleotide panels). Immunohistochemistry (IHC) was employed to perform mismatch repair protein testing in 1976 samples. RESULTS: We collected 2572 patients with CRC and GC. The National Cancer Institute (NCI) panel failed to detect 13 cases. Of the 2559 cases that received results from all three panels, 2544 showed consistent results. In the remaining 15 cases, 9 showed discrepancies between MSI-H and MSI-L, and 6 showed discrepancies between MSI-L and microsatellite stability (MSS). The misdiagnosis rate of MSI-L was significantly lower in two mononucleotide panels than in the NCI panel (12.5% vs 87.5%, p=0.010) in CRC. In patients with GC, only the NCI panel detected three MSI-L cases, while the results of the two mononucleotide panels were one MSI-H and two MSS. Based on their IHC results, the MSI-L misdiagnosis rate of the NCI panel was 33.3%. Furthermore, compared with two mononucleotide panels, the NCI panel had a much lower rate of all loci instability in CRC (90.8% and 90.3% vs 25.2%) and GC (89.5% and 89.5% vs 12.0%). CONCLUSION: In Chinese patients with CRC and GC, the five and six mononucleotide panels have advantages for detecting MSI over the NCI panel.

Analysis of chromosomal structural variations in patients with recurrent spontaneous abortion using optical genome mapping.

Background and aims: Certain chromosomal structural variations (SVs) in biological parents can lead to recurrent spontaneous abortions (RSAs). Unequal crossing over during meiosis can result in the unbalanced rearrangement of gamete chromosomes such as duplication or deletion. Unfortunately, routine techniques such as karyotyping, fluorescence in situ hybridization (FISH), chromosomal microarray analysis (CMA), and copy number variation sequencing (CNV-seq) cannot detect all types of SVs. In this study, we show that optical genome mapping (OGM) quickly and accurately detects SVs for RSA patients with a high resolution and provides more information about the breakpoint regions at gene level. Methods: Seven couples who had suffered RSA with unbalanced chromosomal rearrangements of aborted embryos were recruited, and ultra-high molecular weight (UHMW) DNA was isolated from their peripheral blood. The consensus genome map was created by de novo assembly on the Bionano Solve data analysis software. SVs and breakpoints were identified via alignments of the reference genome GRCh38/hg38. The exact breakpoint sequences were verified using either Oxford Nanopore sequencing or Sanger sequencing. Results: Various SVs in the recruited couples were successfully detected by OGM. Also, additional complex chromosomal rearrangement (CCRs) and four cryptic balanced reciprocal translocations (BRTs) were revealed, further refining the underlying genetic causes of RSA. Two of the disrupted genes identified in this study, FOXK2 [46,XY,t(7; 17)(q31.3; q25)] and PLXDC2 [46,XX,t(10; 16)(p12.31; q23.1)], had been previously shown to be associated with male fertility and embryo transit. Conclusion: OGM accurately detects chromosomal SVs, especially cryptic BRTs and CCRs. It is a useful complement to routine human genetic diagnostics, such as karyotyping, and detects cryptic BRTs and CCRs more accurately than routine genetic diagnostics.

Regional odontodysplasia on the left side of the mandible: report of an unusual case.

Regional odontodysplasia (RO) is a rare developmental abnormality of epithelial and mesenchymal dental tissues. Due to its poorly understood etiology, assessing and discussing related clinical cases of this dental anomaly is crucial to guide professionals in improving its treatment and outcomes. This article aimed to report the case of a 9-year-old male patient who presented to our department with the main complaint of absent eruption of permanent left mandibular quadrant teeth. This is the first case reported in China from a patient with multiple cutaneous nevi on the face and neck, and based on the retrieved clinical and radiographic features, we described and discussed the treatment and etiology of RO.

PRM-based quantitative proteomics analysis of altered HSP abundance in villi and decidua of patients with early missed abortion.

OBJECTIVE: In this study, we aimed to identify differentially expressed heat shock protein (HSP) profiles in the villi and decidua from patients with early missed abortion (EMA). METHODS: By using high-throughput and high-precision parallel reaction monitoring (PRM)-based targeted proteomics techniques, this study examined the abundance of HSPs in the villi and decidua of 10 patients with EMA and 10 controls. Moreover, the abundance of 3 HSPs in the villi of another 22 patients with EMA and 22 controls was verified with Western blotting and immunohistochemistry (IHC). RESULTS: There were potential differences in the abundance of 16 HSPs and 42 polypeptides in human villi and decidua compared with those of the control group. Among them, HSP90AB1, HSPD1 and HSPA13 were downregulated in abundance in villi of patients with EMA, with a statistically significant difference, which was consistent with the verification results of Western blots and IHC. CONCLUSION: Using a PRM-based targeted proteomics technique, this study is the first to screen and quantitatively analyze the expression profile of HSPs in the villi and decidua of patients with EMA. The significant downregulation of HSP90AB1, HSPD1 and HSPA13 was found to have a potentially intimate association with the occurrence of EMA. The findings in our study may provide novel potential research targets related to HSPs for the pathogenesis, prevention and treatment of EMA.

Association between aberrant amino acid metabolism and nonchromosomal modifications fetal structural anomalies: A cohort study.

Background: More than half of the cases of fetal structural anomalies have no known cause with standard investigations like karyotype testing and chromosomal microarray. The differential metabolic profiles of amniotic fluid (AF) and maternal blood may reveal valuable information about the physiological processes of fetal development, which may provide valuable biomarkers for fetal health diagnostics. Methods: This cohort study of singleton-pregnant women had indications for amniocentesis, including structural anomalies and a positive result from maternal serum screening or non-invasive prenatal testing, but did not have any positive abnormal karyotype or chromosomal microarray analysis results. A total of 1580 participants were enrolled between June 2021 and March 2022. Of the 1580 pregnant women who underwent amniocentesis, 294 were included in the analysis. There were 137 pregnant women in the discovery cohort and 157 in the validation cohort. Results: High-coverage untargeted metabolomic analysis of AF revealed distinct metabolic signatures with 321 of the 602 metabolites measured (53%) (false discovery rate, q < 0.005), among which amino acids predominantly changed in structural anomalies. Targeted metabolomics identified glutamate and glutamine as novel predictive markers for structural anomalies, their vital role was also confirmed in the validation cohort with great predictive ability, and the area under the receiver operating characteristic curves (AUCs) were 0.862 and 0.894 respectively. And AUCs for glutamine/glutamate were 0.913 and 0.903 among the two cohorts. Conclusions: Our results suggested that the aberrant glutamine/glutamate metabolism in AF is associated with nonchromosomal modificantions fetal structural anomalies. Based on our findings, a novel screening method could be established for the nonchromosomal modificantions fetal structural anomalies. And the results also indicate that monitoring fetal metabolic conditions (especially glutamine and glutamine metabolism) may be helpful for antenatal diagnosis and therapy.

Engineering Escherichia coli to Utilize Erythritol as Sole Carbon Source.

Erythritol, one of the natural sugar alcohols, is widely used as a sugar substitute sweetener in food industries. Humans themselves are not able to catabolize erythritol and their gut microbes lack related catabolic pathways either to metabolize erythritol. Here, Escherichia coli (E. coli) is engineered to utilize erythritol as sole carbon source aiming for defined applications. First, the erythritol metabolic gene cluster is isolated and the erythritol-binding transcriptional repressor and its DNA-binding site are experimentally characterized. Transcriptome analysis suggests that carbohydrate metabolism-related genes in the engineered E. coli are overall upregulated. In particular, the enzymes of transaldolase (talA and talB) and transketolase (tktA and tktB) are notably overexpressed (e.g., the expression of tktB is improved by nearly sixfold). By overexpression of the four genes, cell growth can be increased as high as three times compared to the cell cultivation without overexpression. Finally, engineered E. coli strains can be used as a living detector to distinguish erythritol-containing soda soft drinks and can grow in the simulated intestinal fluid supplemented with erythritol. This work is expected to inspire the engineering of more hosts to respond and utilize erythritol for broad applications in metabolic engineering, synthetic biology, and biomedical engineering.

The Microzone Structure Regulation of Diamond/Cu-B Composites for High Thermal Conductivity: Combining Experiments and First-Principles Calculations.

The interface microzone characteristics determine the thermophysical properties of diamond/Cu composites, while the mechanisms of interface formation and heat transport still need to be revealed. Here, diamond/Cu-B composites with different boron content were prepared by vacuum pressure infiltration. Diamond/Cu-B composites up to 694 W/(mK) were obtained. The interfacial carbides formation process and the enhancement mechanisms of interfacial heat conduction in diamond/Cu-B composites were studied by HRTEM and first-principles calculations. It is demonstrated that boron can diffuse toward the interface region with an energy barrier of 0.87 eV, and these elements are energetically favorable to form the B4C phase. The calculation of the phonon spectrum proves that the B4C phonon spectrum is distributed in the range of the copper and diamond phonon spectrum. The overlapping of phonon spectra and the dentate structure together enhance the interface phononic transport efficiency, thereby improving the interface thermal conductance.

Screening and mutation analysis of phenylalanine hydroxylase deficiency in newborns from Jiangxi province.

Background: Phenylalanine hydroxylase deficiency (PAHD) is an autosomal recessive disorder of amino acid metabolism and caused by mutations in the phenylalanine hydroxylase (PAH) gene. Without timely and appropriate dietary management, the disturbance of amino acid metabolism may impair cognitive development and neurophysiological function. Newborn screening (NBS) can aid the early diagnosis of PAHD, which can give accurate therapy to PAHD patients in time. In China, the PAHD incidence and PAH mutation spectrum vary enormously across the provinces. A total of 5,541,627 newborns from Jiangxi province were screened by NBS between 1997 and 2021. Method: One seventy one newborns from Jiangxi province were diagnosed with PAHD. By Sanger sequencing and the multiplex ligation-dependent probe amplification (MLPA) analysis, mutation analysis was performed in 123 PAHD patients. Using an arbitrary values (AV)-based model, we compared the observed phenotype with the predicted phenotype based on the genotype. Results: In this study, we speculated the PAHD incidence of Jiangxi province was about 30.9 per 1,000,000 live births (171/5,541,627). We summarized the PAH mutation spectrum in Jiangxi province for the first time. Two novel variants (c.433G > C, c.706 + 2T > A) were found. The most prevalent variant was c.728G > A (14.1%). The overall prediction rate of the genotype-phenotype was 77.4%. Conclusion: This mutation spectrum is very meaningful to improve the diagnostic rate of PAHD and to increase the accuracy genetic counseling. This study offers data for the genotype-phenotype prediction suitable for Chinese population.

Radioactive Iodine Therapy Decreases the Recurrence of Intermediate-Risk PTC With Low Thyroglobulin Levels.

CONTEXT: Whether radioactive iodine therapy (RAIT) is necessary for intermediate-risk papillary thyroid cancer (PTC) after total thyroidectomy is still lacking reliable evidence, especially for patients with low postoperative thyroglobulin (Tg) levels. OBJECTIVE: This study conducted a propensity score matching (PSM) analysis to investigate whether RAIT is effective in reducing the recurrence of intermediate-risk PTC with low Tg levels. METHODS: In total, 1487 patients with intermediate-risk PTC with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL after total thyroidectomy were enrolled retrospectively. The clinicopathological characteristics were compared between the non-RAIT and RAIT groups before and after PSM (1:4 matching). The impact of RAIT on biochemical recurrence and structural recurrence was evaluated. RESULTS: Overall, 1349 (90.7%) patients underwent RAIT, and 138 (9.3%) did not. After a median follow-up time of 51 months, 30 patients presented with recurrence, including 11 structural and 19 biochemical recurrences. After PSM, the non-RAIT group had a higher rate of structural recurrence (5/138 vs 5/552, P = .046) and biochemical recurrence (6/138 vs 4/552, P = .005) than the RAIT group. Multivariate analysis showed that not receiving RAIT was an independent risk factor for structural recurrence (hazard ratio [HR] 10.572, 95% CI 2.439-45.843, P = .002) and biochemical recurrence (HR 16.568, 95% CI 3.670-74.803, P < .001). Kaplan-Meier analysis showed that the non-RAIT group had more unfavorable recurrence-free survival (structural and biochemical, all P < .05). CONCLUSION: RAIT could decrease the recurrence risk of intermediate-risk PTC in patients with unstimulated Tg ≤ 1 ng/mL or stimulated Tg ≤ 10 ng/mL. Further prospective randomized studies are needed to confirm these findings.

Comparative Study of Initial Post-Therapeutic 131I Single-Photon Emission Computed Tomography/Computed Tomography and Reoperation for the Detection of Residual Lymph Node Metastasis in Patients With Papillary Thyroid Cancer.

OBJECTIVE: To assess the diagnostic performance of initial post-therapeutic 131I single-photon emission computed tomography/computed tomography (SPECT/CT) compared with that of reoperation in detecting residual lymph node metastasis (LNM). METHODS: Patients with iodine-avid LNM detected on the initial post-therapeutic 131I SPECT/CT and who underwent reoperative dissection within 6 months were included. LNMs (numbers and locations) detected via both methods were compared. The American Thyroid Association dynamic risk stratification was performed for patients receiving second radioactive iodine therapy after reoperation. RESULTS: Fifty-three patients with 95 iodine-avid LNMs detected by 131I SPECT/CT were enrolled. Fifty-one (96.2%) patients had 212 LNMs confirmed by reoperation (P = .004). The sensitivity and specificity of 131I SPECT/CT in detecting LNM were 44.8% (95/212) and 91.6% (87/95), respectively. The location frequency of residual LNMs found by 131I SPECT/CT was similar to that of reoperation (P = .057). Thirty-two patients received a second radioactive iodine treatment, and 6 (18.8%) patients still had residual iodine-avid LNM on SPECT/CT. Therapeutic response was evaluated by American Thyroid Association dynamic risk stratification in 16 patients. The number of patients with structural incomplete response, biochemical incomplete response, indeterminate response, and excellent response was 4 (23.5%), 4 (23.5%), 5 (29.4%), and 3 (17.6%), respectively. CONCLUSION: 131I SPECT/CT has high specificity but relatively low sensitivity in detecting all residual LNMs. Approximately 80% of patients were rendered structurally disease free after reoperation.