Clinical Trial: Magnetoplasmonic ELISA for Urine-based Active Tuberculosis Detection and Anti-Tuberculosis Therapy Monitoring.

The coronavirus disease 2019 (COVID-19) pandemic has proved the importance of fast and widespread diagnostic testing to prevent serious epidemics timely. The first-line weapon against rapidly transmitted disease is a quick and massive screening test to isolate patients immediately, preventing dissemination. Here, we described magnetoplasmonic nanozymes (MagPlas NZs), i.e., hierarchically coassembled Fe3O4-Au superparticles, that are capable of integrating magnetic enrichment and catalytic amplification, thereby the assay can be streamlined amenable to high-throughput operation and achieve ultrahigh sensitivity. Combining this advantage with conventional enzyme-linked immunosorbent assay (ELISA), we propose a MagPlas ELISA for urine-based tuberculosis (TB) diagnosis and anti-TB therapy monitoring, which enables fast (<3 h), and highly sensitive (up to pM with naked-eyes, < 10 fM with plate reader) urinary TB antigen detection. A clinical study with a total of 297 urine samples showed robust sensitivity for pulmonary tuberculosis (85.0%) and extra-pulmonary tuberculosis (52.8%) patients with high specificity (96.7% and 96.9%). Furthermore, this methodology offers a great promise of noninvasive therapeutic response monitoring, which is impracticable in the gold-standard culture method. The MagPlas ELISA showed high sensitivity comparable to the PCR assay while retaining a simple and cheap ELISA concept, thus it could be a promising point-of-care test for TB epidemic control and possibly applied to other acute infections.

Scalable Solvothermal Synthesis of Superparamagnetic Fe3O4 Nanoclusters for Bioseparation and Theragnostic Probes.

Magnetic nanoparticles have had a significant impact on a wide range of advanced applications in the academic and industrial fields. In particular, in nanomedicine, the nanoparticles require specific properties, including hydrophilic behavior, uniform and tunable dimensions, and good magnetic properties, which are still challenging to achieve by industrial-scale synthesis. Here, we report a gram-scale synthesis of hydrophilic magnetic nanoclusters based on a one-pot solvothermal system. Using this approach, we achieved the nanoclusters with controlled size composed of magnetite nanocrystals in close-packed superstructures that exhibited hydrophilicity, superparamagnetism, high magnetization, and colloidal stability. The proposed solvothermal method is found to be highly suitable for synthesizing industrial quantities (gram-per-batch level) of magnetic spheres with unchanged structural and magnetic properties. Furthermore, coating the magnetic spheres with an additional silica layer provided further stability and specific functionalities favorable for biological applications. Using in vitro and in vivo studies, we successfully demonstrated both positive and negative separation and the use of the magnetic nanoclusters as a theragnostic nanoprobe. This scalable synthetic procedure is expected to be highly suitable for widespread use in biomedical, energy storage, photonics, and catalysis fields, among others.

Magnetic Nanozyme-Linked Immunosorbent Assay for Ultrasensitive Influenza A Virus Detection.

Rapid and sensitive detection of influenza virus is of soaring importance to prevent further spread of infections and adequate clinical treatment. Herein, an ultrasensitive colorimetric assay called magnetic nano(e)zyme-linked immunosorbent assay (MagLISA) is suggested, in which silica-shelled magnetic nanobeads (MagNBs) and gold nanoparticles are combined to monitor influenza A virus up to femtogram per milliliter concentration. Two essential strategies for ultrasensitive sensing are designed, i.e., facile target separation by MagNBs and signal amplification by the enzymelike activity of gold nanozymes (AuNZs). The enzymelike activity was experimentally and computationally evaluated, where the catalyticity of AuNZ was tremendously stronger than that of normal biological enzymes. In the spiked test, a straightforward linearity was presented in the range of 5.0 × 10-15-5.0 × 10-6g·mL-1 in detecting the influenza virus A (New Caledonia/20/1999) (H1N1). The detection limit is up to 5.0 × 10-12 g·mL-1 only by human eyes, as well as up to 44.2 × 10-15 g·mL-1 by a microplate reader, which is the lowest record to monitor influenza virus using enzyme-linked immunosorbent assay-based technology as far as we know. Clinically isolated human serum samples were successfully observed at the detection limit of 2.6 PFU·mL-1. This novel MagLISA demonstrates, therefore, a robust sensing platform possessing the advances of fathomable sample separation, enrichment, ultrasensitive readout, and anti-interference ability may reduce the spread of influenza virus and provide immediate clinical treatment.

Outcome prediction with the revised American joint committee on cancer staging system and American thyroid association guidelines for thyroid cancer.

BACKGROUND: Several staging systems have been developed to predict the risk of mortality in patients with differentiated thyroid cancer (DTC). However, none of them have been shown to be clearly superior to the other. METHODS: We compared the patient outcome predictability of recently revised staging systems predictability of patient outcome using data from The Cancer Genome Atlas. To set a comparison among American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging 7th, 8th editions, American Thyroid Association guidelines 2009 and 2015, concordance index (c-index), Akaike information criterion (AIC), Bayesian information criterion (BIC), and Brier score were applied to quantify the predictive ability of a survival model, to select the statistical model, and to measure the accuracy of probabilistic predictions. RESULTS: A total of 457 patients with papillary thyroid cancer having a mean age of 45.9 years were included in this study (120 males, 337 females). Among these patients, 43 (9.4%) experienced recurrence/progression during the follow-up (591.2 ± 833.5 months). Among the models used, the AJCC/UICC 8th edition, which showed the highest c-index and lowest AIC, BIC, and Brier score, was identified as the best among the models used. CONCLUSION: AJCC/UICC 8th edition predicted patient outcome more accurately than the other staging systems.

Voice outcome according to surgical extent of transoral laser microsurgery for T1 glottic carcinoma.

OBJECTIVES/HYPOTHESIS: To evaluate the outcomes of transoral laser microsurgery (TLM) for T1 glottic carcinoma using longitudinal voice analysis. STUDY DESIGN: Retrospective analysis of medical records. METHODS: We conducted a retrospective review of 57 patients (50 T1a, seven T1b) who underwent TLM for T1 glottic carcinoma, and longitudinal voice analysis was performed before surgery, during the early postoperative period (within 3 months), and during the late postoperative period (more than 6 months). Acoustic, perceptual (Grade, Roughness, Breathiness, Asthenia, Strain scale), and subjective voice analysis using the Voice Handicap Index (VHI) was conducted. RESULTS: Voice quality deteriorated in the early postoperative period in terms of several parameters. However, no significant differences in voice quality were observed in the late postoperative period, whereas Grade (from 1.85 ± 0.83 to 1.50 ± 0.90) and Roughness (from 1.74 ± 0.73 to 1.48 ± 0.87) had improved significantly. Patients who underwent lesser-extent cordectomy (type I, II) showed improvement in VHI-Physical (from 12.93 ± 11.10 to 6.07 ± 8.69) and Grade (from 1.60 ± 0.68 to 0.98 ± 0.83), whereas improvement was not identified in those who underwent larger-extent cordectomy (type III, IV, V). Improvement in Grade (from 1.70 ± 0.80 to 1.23 ± 0.91) and Roughness (from 1.77 ± 0.73 to 1.25 ± 0.76) was identified in patients who had unilateral tumor without involvement of anterior commissure. However, those with involvement of the anterior commissure or bilateral vocal cord showed a tendency toward deterioration in voice quality. CONCLUSIONS: Voice quality of patients following TLM for T1 glottic carcinoma may improve significantly over time in cases with lesser-extent types of cordectomy or unilateral tumor without involvement of the anterior commissure. LEVEL OF EVIDENCE: 4 Laryngoscope, 126:2051-2056, 2016.

Pathologic features of metastatic lymph nodes identified from prophylactic central neck dissection in patients with papillary thyroid carcinoma.

The importance of pathologic features of metastatic lymph nodes (LNs), such as size, number, and extranodal extension, has been recently emphasized in patients with papillary thyroid carcinoma (PTC). We evaluated the characteristics of metastatic LNs identified after prophylactic central neck dissection (CND) in patients with PTC. We performed a retrospective review of 1,046 patients who underwent unilateral or bilateral thyroidectomy with ipsilateral prophylactic CND. We reviewed the characteristics of the metastatic LNs and analyzed their correlation to the clinicopathologic characteristics of the primary tumor. Cervical LN metastasis after prophylactic CND was identified in 280 out of 1046 patients (26.8 %). The size of metastatic foci (≥2 mm) was independently correlated with primary tumor size (≥1 cm) (p = 0.016, OR = 1.88). Primary tumor size (≥1 cm) was also correlated to the number of metastatic LNs (≥5) (p = 0.004, OR = 3.14) and extranodal extension (p = 0.021, OR = 2.41) in univariate analysis. The size of the primary tumor affects pathologic features of subclinical LN metastasis in patients with PTC. Patients with primary tumors ≥1 cm have an increased risk of larger LN metastases (≥2 mm), an increased number of LN metastases (≥5), and a higher incidence of ENE, which should be considered in decision for prophylactic CND.

Clinical significance of melanoma-associated antigen A1-6 expression in sputum of patients with squamous cell carcinoma of the larynx and hypopharynx.

BACKGROUND: Several studies have reported the expression of the melanoma-associated antigen (MAGE) gene in head and neck squamous cell carcinoma (HNSCC). In this study, we evaluated the correlations between MAGE expression in sputum and the clinical features and oncologic outcomes of SCC of the larynx and hypopharynx. METHODS: We performed a retrospective review of 119 patients treated for SCC of the larynx and hypopharynx and analysis of their induced sputum by nested reverse transcription-polymerase chain reaction (RT-PCR) to detect the MAGE-A1-6 gene. The associations between MAGE expression and clinical characteristics were analyzed. RESULTS: Expression of MAGE-A1-6 in sputum was identified in 57 of 119 patients (47.9%), and was independently correlated to double primary cancer (p = .024; odds ratio [OR] = 4.135). Expression of MAGE-A1-6 in sputum was correlated to poor survival. CONCLUSION: Expression of MAGE-A1-6 in sputum predicts poor oncologic outcome in patients with SCC of the larynx and hypopharynx. © 2015 Wiley Periodicals, Inc. Head Neck 38: E736-E740, 2016.

Correlation of minimal extrathyroidal extension with pathologic features of lymph node metastasis in patients with papillary thyroid carcinoma.

BACKGROUND: The impact of minimal extrathyroidal extension (mETE) to the prognosis of patients with papillary thyroid carcinoma (PTC) is controversial. In this study, we investigated whether mETE is related to the aggressive biology of metastatic lymph node (LN) in patients with PTC. METHODS: A retrospective review of 369 patients who had biopsy-confirmed cervical LN metastasis after initial surgery for PTC was conducted. The correlations of mETE with the specific features of metastatic LNs such as the LN size, number, LN ratio, and presence of extranodal extension (ENE) were statistically analyzed. RESULTS: Size of the primary tumor (≥1 cm) had independent correlations to mETE (HR = 5.750). While mETE was related to number of metastatic LNs (≥5), LN ratio (≥0.31) and ENE in univariate analysis, only ENE (HR = 2.322) was independently correlated to mETE in our series. Along with mETE, size of primary tumor (≥1 cm) had significant impact on ENE (HR = 2.107). CONCLUSION: Minimal ETE particularly those with larger primary tumor (≥1 cm) may be still considered as a significant factor regarding the management of cervical LNs in patients with PTC.

Endoscope-assisted transoral removal of a thyroglossal duct cyst using a frenotomy incision: A prospective clinical trial.

OBJECTIVES/HYPOTHESIS: Endoscope-assisted transoral removal of a thyroglossal duct cyst (TGDC) has been introduced to clinical practice. However, the technical feasibility, efficacy, and safety of this procedure have not been studied. Herein, we conducted a prospective clinical trial to evaluate endoscope-assisted transoral removal of a TGDC. STUDY DESIGN: Prospective cohort study. METHODS: Thirty patients were included. We performed endoscope-assisted transoral removal of TGDCs and evaluated the clinical results and complications over more than 2 years. RESULTS: Endoscope-assisted transoral resection was successful in all cases. However, transient morbidity was noted in one patient. The mean operation time was 67.33 ± 17.26 minutes. Surgery was not required for recurrence or revision during a follow-up. CONCLUSIONS: Endoscope-assisted transoral resection of a TGDC is a potentially safe and effective procedure leading to excellent functional and cosmetic outcomes. Additionally, considering the embryological development of TGDCs, the transoral approach can open a new access route to these cysts. LEVEL OF EVIDENCE: 2b.

Efficacy of ethanol ablation for thyroglossal duct cyst.

OBJECTIVE: Ethanol ablation has been known as an effective, easy, and safe treatment of cystic thyroid lesions. The objective of the present study was to evaluate efficacy of ethanol ablation as a minimally invasive management of thyroglossal duct cyst (TGDC). METHODS: Between January 2012 and July 2013, 9 TGDC patients were diagnosed and treated with ethanol ablation. We evaluated the treatment outcomes with the change of volume reduction and the improvement of symptomatic and cosmetic complaints and complications. RESULTS: Initial mean tumor volume was 8.9 mL (range, 0.2-36.9 mL) in ultrasonography. The mean number of the treatment sessions was 1.7 (range, 1-3 sessions). At last follow-up, the mean volume of the treated thyroglossal duct cyst decreased significantly from 8.9 mL to 1.9 mL (P = .019; volume reduction rate = 76.6%). Treatment success rate was 77.8% (7/9). Mean symptoms and cosmetic-grading scores improved from 5.2 to 3.1 and from 5.3 to 3.1 (P = .062). No significant complications were observed during follow-up. CONCLUSION: Ethanol ablation is a feasible and convenient procedure without surgical scars and hospitalization for TGDC patients. Favorable outcomes can be achieved without significant complications.

Papillary thyroid carcinoma with exclusive involvement of a functioning recurrent laryngeal nerve may be treated with shaving technique.

OBJECTIVES: We sought to validate the feasibility of preserving a functioning recurrent laryngeal nerve (RLN) invaded by papillary thyroid carcinoma (PTC) using a shaving technique followed by high-dose radioactive iodine (RAI) therapy. METHODS: A retrospective review of 34 patients with locally invasive PTC who had exclusive tumor involvement of a functioning RLN was performed. All patients underwent total thyroidectomy and high-dose RAI therapy. A shaving technique was conducted with the goal of leaving the smallest amount of residual tumor as possible while attempting to preserve nerve function. Clinicopathologic factors and oncologic outcomes of the patients with resected RLN (group A, n = 14) and preserved RLN (group B, n = 20) were compared. RESULTS: The two groups showed no differences in clinicopathologic factors or follow-up period. Mean dose of radioiodine therapy was 245.0 ± 140.3 mCi (range 100-540 mCi). Permanent postoperative vocal cord paralysis after RLN shaving occurred in two patients of group B (10%). Only one patient (5%) in group B had local recurrence at the thyroid bed where the residual tumor was located. The overall recurrence rate was 35.7% (5/14) and 20.0% (4/20) in groups A and B, respectively showing no significant difference (p = 0.525). There were no cases of death due to PTC during the median follow-up of 75 months (range 36-159 months). CONCLUSIONS: Patients with locally invasive PTC with exclusive involvement of a functioning RLN may be treated by nerve shaving followed by treatment of the macroscopic residual tumor with high-dose RAI therapy.

Partial cutting of sternothyroid muscle during total thyroidectomy: impact on postoperative vocal outcomes.

BACKGROUND: Cutting the sternothyroid (ST) muscle is a useful technique to expose the superior pole of thyroid gland during thyroidectomy. In this study, we evaluated the impact of partial cutting of the ST muscle on postoperative vocal outcomes after total thyroidectomy. METHODS: A retrospective review of 57 patients who underwent total thyroidectomy with central neck dissection for micropapillary thyroid carcinoma was conducted. Group A (n = 26) included those without cutting the ST muscle, while group B (n = 31) included patients whose muscle was partially cut at the superior pole. All patients underwent voice analysis before the operation and 2 weeks and 1 month after the surgery, and the outcomes were compared between the two groups. RESULTS: There were no differences between the two groups regarding the outcomes at each time of voice analysis. Group A showed a decrease of maximum frequency 2 weeks after surgery but showed no difference after 1 month. Group B showed a mild decrease in maximum frequency 2 weeks after surgery, but the difference was not significant. CONCLUSION: Partial cutting of ST muscle during thyroidectomy is useful to expose the superior pole without significant negative impact on postoperative outcomes of vocal analysis.

The relationship between the BRAF(V600E) mutation in papillary thyroid microcarcinoma and clinicopathologic factors.

BACKGROUND: The BRAF(V600E) mutation, which accounts for about 60-80% papillary thyroid carcinoma(PTC), has been identifiedas a prognostic marker for risk stratification of PTC patients. However, the BRAF(V600E) mutation as a prognostic marker in papillary thyroid microcarcinoma (PTMC) is unclear. METHODS: We performed a retrospective review of 101 patients who underwent surgery for PTMC. We studied the prevalence of the BRAF(V600E) mutation. The associations between the BRAF(V600E) mutation and clinicopathologic characteristics were analyzed. RESULTS: The BRAF(V600E) mutation was observed in 72 patients (71.3%). There was no statistically significant correlation in age, gender, multifocality, extrathyroidal extension, presence of Hashimoto thyroiditis, and lymph node metastasis between the BRAF(V600E) mutant group and wild group. CONCLUSIONS: The BRAF(V600E) mutation is not significantly associated with prognostic factors in PTMC.

Clinical characteristics of papillary thyroid microcarcinoma less than or equal to 5 mm on ultrasonography.

Management of papillary thyroid microcarcinoma sized ≤5 mm identified on ultrasonography is controversial. In this study, we evaluated the clinical characteristics of papillary thyroid microcarcinoma sized ≤5 mm on ultrasonography in comparison to those >5 mm and sought to present rationales for optimal management in papillary thyroid microcarcinoma ≤5 mm. The medical records of 396 patients who underwent surgery for papillary thyroid carcinoma between 2009 and 2011 were retrospectively analyzed. The patients were grouped into A (≤5 mm, n = 132) or B (>5 mm, n = 264) and the clinicopathologic characteristics of the patients were reviewed and compared between the two groups. Tumor capsular invasion (45.5 vs. 59.8 %, p = 0.007) and cervical lymph node metastasis (18.2 vs. 29.2 %, p = 0.018) were more frequent in group B. Nonetheless, group A presented lymph node metastasis in 42.3 % of multifocal cases showing no difference to that of group B (41.5 %, p = 0.946) and also included five cases (3.8 %) of lateral neck metastasis. Multifocality was the only predictive factor for lymph node metastasis in group A (p < 0.001). Over half (55.3 %) of the patients of group A were diagnosed with papillary carcinoma in private clinics; however, only 5.5 % of these patients underwent assessment of lateral neck lymph nodes initially. In conclusion, higher risk of cervical lymph node metastasis should be considered in evaluation and surgical decision of papillary thyroid microcarcinoma ≤5 mm identified on ultrasonography with multifocality. Evaluation of the cervical lymph nodes including the lateral neck should not be overlooked when suspicious thyroid nodule suggesting malignancy sized ≤5 mm shows multifocal lesions.

Transoral laser microsurgery for early glottic cancer as one-stage single-modality therapy.

OBJECTIVES/HYPOTHESIS: A study was undertaken to determine the oncologic outcomes in a consecutive series of early glottic carcinomas treated with transoral CO2 laser microsurgery (TLM) as a one-stage single-modality therapy, without any postoperative radiation therapy or retreatment with laser. We further evaluated correlations between the oncologic outcomes and clinicopathologic factors including tumor location and surgical margin. STUDY DESIGN: Retrospective analysis of medical records. METHODS: The medical records of 118 consecutive patients with early stage (T1, T2) glottic carcinoma who underwent TLM by a single surgeon as an initial treatment from 1997 to 2011 were retrospectively reviewed. The oncologic outcomes were evaluated, and correlations to clinicopathologic factors were analyzed. RESULTS: The 5-year disease-free survival, ultimate local control with laser alone, disease-specific survival, overall survival, and organ preservation rates were 87.9%, 94.2%, 99.0%, 92.2%, and 96.2%, respectively. Neither the reported surgical margin nor the extension of tumor to the anterior commissure, arytenoid, subglottis, and ventricle showed any significant impact on local control or survival. CONCLUSIONS: Transoral CO2 laser microsurgery as one-stage single-modality therapy resulted in a high rate of local control and a high survival rate in selected cases of early glottic carcinoma, regardless of the location of tumor and histopathology report on the surgical margin.

Expression of MAGE A1-6 and the clinical characteristics of papillary thyroid carcinoma.

BACKGROUND: The expression of melanoma-associated antigen (MAGE) gene has been studied in many types of cancer. In the present study we evaluated the correlation between MAGE expression and the clinical features and oncologic outcomes of patients with papillary thyroid cancer (PTC). MATERIALS AND METHODS: We performed a retrospective review of 85 patients who underwent surgery for PTC and analysis of their tumor tissue by nested reverse transcription-polymerase chain reaction (RT-PCR) with the MAGE common primer to detect the MAGE A1-6 gene. The associations between MAGE expression and clinical characteristics were analyzed. RESULTS: Expression of MAGE A1-6 in PTC was identified in 31 patients (36.5%). Only papillary thyroid microcarcinoma (PTMC) was significantly related to MAGE expression in our univariate analysis (p=0.002) and multivariate analysis (p=0.006). MAGE had no significant impact on survival. CONCLUSION: Expression of MAGE A1-6 in PTC is significantly correlated with the presence of PTMC. Our study suggests that MAGE expression may be related to early-stage PTC.

Salvage transoral laser supraglottic laryngectomy after radiation failure: a report of seven cases.

OBJECTIVES: We evaluated the oncological and functional outcomes of salvage transoral laser supraglottic laryngectomy after radiation failure. In addition, we demonstrated the usefulness of laser surgery in patients with recurrent supraglottic cancer. METHODS: Between December 1999 and May 2011,7 patients (6 men and 1 woman) underwent transoral laser supraglottic laryngectomy after radiation failure. We conducted 4 different types of endoscopic supraglottic laryngectomy. In the cases with lymph node metastasis, we performed neck dissection at the time of laser surgery. RESULTS: All patients had recurrent squamous cell carcinoma confirmed on the surgical specimen. Two patients were classified as having T1 disease, 2 as having T2 disease, and 3 as having T3 disease with preepiglottic space involvement. The 2- and 5-year overall survival rates were 85.7% and 68.6%, respectively. There was a recurrence at 8 months of followup after laser surgery in 1 patient; he underwent successful salvage total laryngectomy. The ultimate local control rate was 100%, and the laryngeal preservation rate was 85.7%. The hospitalization times ranged from 2 to 32 days (mean, 15.6 days). The mean decannulation time was 10.7 days (range, 5 to 30 days). All patients started oral feeding within 1 to 3 days after surgery. CONCLUSIONS: Salvage transoral laser supraglottic laryngectomy following radiation failure seems a feasible and oncologically safe procedure in recurrent supraglottic cancers ranging from T1 to selected T3 with minimal preepiglottic space involvement. It can be an option for minimally invasive organ preservation surgery with lesser morbidity for recurrent supraglottic cancer.

Robot-assisted thyroidectomy: early experience.

BACKGROUND: The numbers of thyroid surgeries have been increasing recently. Robot-assisted thyroidectomy allows for a better cosmetic outcome in comparison with conventional open thyroidectomy. METHODS: We performed two robot-assisted endoscopic thyroidectomies by a gasless unilateral axillo-breast approach using the da Vinci surgical robot system. RESULTS: We performed right thyroid lobectomies in both patients. The pathologic reports were: micropapillary carcinoma without extracapsular invasion in patient 1 and a benign cyst in patient 2. The operation times were 165 minutes in patient 1 and 110 minutes in patient 2. No postoperative complications occurred. CONCLUSION: Regarding our early experience, robotic thyroidectomy using the gasless axillo-breast approach is a safe, feasible, and cosmetically good procedure.