A New Equation to Estimate Peripherally Inserted Central Catheter Length.

Background and Objectives: Peripherally inserted central catheter (PICC) placement plays an important role in clinical practice. This study aimed to provide an equation for the proper estimation of catheter length in cases of PICC placement without imaging guidance in relation to patient height, weight, sex, and age. Materials and Methods: For 1137 PICC placement cases in both arm veins of 954 patients at a single center, the elbow crease to the cavoatrial junction length (ECL) was calculated as follows: ECL = (PICC length) + (distance from the elbow crease to the puncture site). We analyzed the relationship between ECL and patient characteristics and suggested a new equation for ECL based on height, weight, sex, and age. Results: The average ECL was 48.0 ± 2.4 cm in the right side and 51.0 ± 3.0 cm in the left side. ECL in the right arm was significantly correlated with patient height, sex, and age, whereas the ECL in the left arm was additionally significantly correlated with patient weight. The ECL (cm) prediction model was as follows: right ECL = 26.32 + 1.33 × (female = 1, male = 2) - 0.02 × age (years) + 0.13 × height (cm); left ECL = 22.09 + 1.28 × (female = 1, male = 2) + 0.02 × age (years) + 0.14 × height (cm) + 0.042 × weight (kg). Conclusions: The appropriate PICC length was predicted based on the patient's height, weight, sex, and age. The equations in our study can help predict the optimal catheter length and can be automatically calculated using computerized patient information for bedside procedures in PICC.

Prognostic implication of early recurrence after cryoballoon ablation in patients with atrial fibrillation.

BACKGROUND: It remains uncertain whether the implication of early recurrence and blanking period can be applied to patients with atrial fibrillation (AF) treated with cryoballoon ablation (CBA). We aimed to explore the prognostic value of early recurrence in patients with AF treated with CBA. METHODS: We studied consecutive AF patients who were treated with CBA between April 2019 and September 2020 in two tertiary medical institutes and followed for up to 12 months. The endpoint was the late recurrence of atrial arrhythmia, including AF, atrial flutter, and atrial tachycardia, following a 90-day blanking period. Atrial arrhythmia during the blanking period was defined as early recurrence and was not considered as an endpoint. RESULTS: This study included 406 patients with AF who underwent CBA. During the follow-up, 147 (36.2%) cases of late recurrence were observed. Of the 104 patients with early recurrence, 85 experienced late recurrence during follow-up. Early recurrence was associated with an increased risk of late recurrence in the univariate and multivariate analyses (P < 0.001). When we classified the patients into paroxysmal AF and persistent AF groups, early recurrence was still significantly associated with a higher risk of late recurrence (P = 0.005 and P < 0.001, respectively). CONCLUSION: Early recurrence after CBA was an independent risk factor for late recurrence in all patients as well as in those with paroxysmal AF and persistent AF. Therefore, further prospective studies could be considered to verify the risks and benefits of early rhythm control in patients with early recurrence.

Adipose-derived, autologous mesenchymal stem cell therapy for patients with post-COVID-19 syndrome: an intermediate-size expanded access program.

BACKGROUND: Evolving mutations of the novel coronavirus continue to fuel up the pandemic. The virus affects the human respiratory system along with other body systems, causing several sequelae in the survivors of the disease, presented as post-COVID-19 syndrome or long-COVID-19. This protocol utilized Hope Biosciences' autologous, adipose-derived mesenchymal stem cells (HB-adMSCs) to evaluate safety and efficacy of HB-adMSC therapy to improve signs and symptoms associated with post-COVID-19 syndrome. METHODS: Ten eligible subjects with post-COVID-19 syndrome were enrolled in the program for a duration of 40 weeks who received 5 intravenous infusions of 2 × 108 autologous HB-adMSCs each at week 0, 2, 6, 10 and 14 with a follow-up at week 18 and end of the study at week 40. Safety assessments included incidence of adverse and serious adverse events along with the laboratory measures of hematologic, hepatic, and renal function. Efficacy was examined by quality-of-life assessments, fatigue assessments, Visual analog scale (VAS) of symptoms and monitoring of respiration and oxygen saturation rates. RESULTS: VAS scores and Fatigue Assessment scores (FAS) showed significant improvements post-treatment (P = 0.0039, ES = 0.91) compared to baseline. Respiration rates and oxygen saturation levels that were within the normal range at the baseline remained unchanged at the end of the study (EOS). Paired comparison between baseline and EOS for short-form-36 health survey questionnaire (SF-36) scores also showed improved quality-of-life with significant improvements in individual SF-36 evaluations. Mostly mild AEs were reported during the study period with no incidence of serious AEs. Also, no detrimental effects in laboratory values were seen. CONCLUSIONS: The results of the expanded access program indicated that treatment with autologous HB-adMSCs resulted in significant improvements in the signs and symptoms associated with post-COVID-19 syndrome as assessed by VAS and FAS scores. Additionally, improvements in the patients' quality-of-life as demonstrated using SF-36 scores that also showed significant improvements in individual scaled scores. Overall, administration of multiple infusions of autologous HB-adMSCs is safe and efficacious for improvements in the quality-of life of patients with post-COVID-19 syndrome. TRIAL REGISTRATION: Clinical trial registration number: NCT04798066. Registered on March 15, 2021. ( https://clinicaltrials.gov/ct2/show/NCT04798066?term=hope+biosciences&cond=Post-COVID-19+Syndrome&draw=2&rank=2 ).

Long-term, repeated doses of intravenous autologous mesenchymal stem cells for a patient with Parkinson's disease: a case report.

Parkinson's disease (PD) is a neurodegenerative disease that involves the loss of dopaminergic neurons in the substantia nigra pars compacta of the basal ganglia. Clinically, patient presentation involves a combination of motor and non-motor symptoms characterized by progressive worsening over time and significant decreases in overall quality-of-life. Despite there being no fully restorative cure for PD, Mesenchymal Stem Cell (MSC) therapy offers promising therapeutic potential. Here, we report a case of a 77-year-old female, living with idiopathic Parkinson's Disease for over 17 years. The patient received multiple infusions of autologous Hope Biosciences adipose-derived MSCs (HB-adMSCs). A total of 26 infusion treatments of HB-adMSCs were administered over the course of ~2 years that resulted in marked improvements in her typical Parkinsonian symptoms, as demonstrated by the decreases in her UPDRS (Unified Parkinson's Disease Rating Scale) scores. Changes in clinical scores mirrored concurrent changes in regional brain metabolism as quantified by FDG-PET (Fluorodeoxyglucose-Positron Emission Tomography), compared to baseline. Long-term, multiple infusions of HB-adMSCs were safely tolerated by the patient without any serious adverse events. Further research is needed to evaluate the safety and efficacy of HB-adMSC therapy for the treatment of PD patients.

Dyslipidemia Is a Risk Factor for Hypothyroidism in Women: A Longitudinal Cohort Study from South Korea.

Background: Hypothyroidism is a risk factor for dyslipidemia. We explored whether dyslipidemia is a risk factor for hypothyroidism. Methods: We performed a retrospective analysis of data from a longitudinal cohort study of South Korean adults who underwent medical examination and ≥4 biochemical assessments of thyroid function. The primary outcome was hypothyroidism (thyrotropin [TSH] >4.2 mU/L), and the secondary outcome was severe subclinical hypothyroidism (SCH; TSH ≥10.0 mU/L and normal free thyroxine [fT4] level) or overt hypothyroidism (OH; total triiodothyronine <80 ng/dL and/or fT4 < 0.93 ng/dL and high TSH values). The association of baseline dyslipidemia status with subsequent hypothyroidism was evaluated using Kaplan-Meier curves with the log-rank test and Cox proportional hazards regression models (for the entire population and respective genders). Subgroup analyses according to age (<40 and ≥40 years) and body-mass index (BMI; <23, 23-25, and ≥25 kg/m2) were performed according to gender. Results: We included 1665 participants. During a median follow-up period of 61.0 months, 24.3% (404/1665) individuals developed hypothyroidism. Among these, 36 participants (2.1%) had severe SCH or OH. Excluding patients with a first abnormal TSH level at last follow-up, 44.5% (126/283) of the patients with hypothyroidism had spontaneous TSH normalization. In respective multivariate analyses, dyslipidemia at baseline was independently associated with development of hypothyroidism in women (adjusted hazard ratio [HR] = 2.05 [1.31-3.19], p = 0.002), but not in men (adjusted HR = 1.00 [0.77-1.30], p = 0.991). In women, the presence of dyslipidemia at baseline was associated with development of severe SCH or OH (adjusted HR = 5.33 [1.41-20.12], p = 0.014). In women, respective associations according to age and BMI were as follows: age <40 years, adjusted HR = 2.90 (1.34-6.26, p = 0.007); age ≥40 years, adjusted HR = 1.85 (1.08-3.14, p = 0.023); BMI <23 kg/m2, adjusted HR = 1.68 (0.82-3.43, p = 0.151); BMI = 23-25 kg/m2, adjusted HR = 2.17 (0.93-5.07, p = 0.071); and BMI ≥25 kg/m2, adjusted HR = 2.82 (1.16-6.86, p = 0.022). Conclusions: In Korean adults, dyslipidemia was associated with development of hypothyroidism in women. Our findings require confirmation.

The Efficacy of Treatment Intensification by Quadruple Oral Therapy Compared to GLP-1RA Therapy in Poorly Controlled Type 2 Diabetes Mellitus Patients: A Real-world Data Study.

We compared the glycemic efficacy of treatment intensification between quadruple oral antidiabetic drug therapy and once-weekly glucagon-like peptide-1 receptor agonist (GLP-1RA)-based triple therapy in patients with poorly controlled type 2 diabetes mellitus refractory to triple oral therapy. For 24 weeks, changes in glycosylated hemoglobin (HbA1c) from baseline were compared between the two treatment groups. Of all 96 patients, 50 patients were treated with quadruple therapy, and 46 were treated with GLP-1RA therapy. Reductions in HbA1c for 24 weeks were comparable (in both, 1.1% reduction from baseline; P=0.59). Meanwhile, lower C-peptide level was associated with a lower glucose-lowering response of GLP-1RA therapy (R=0.3, P=0.04) but not with quadruple therapy (R=-0.13, P=0.40). HbA1c reduction by GLP-1RA therapy was inferior to that by quadruple therapy in the low C-peptide subgroup (mean, -0.1% vs. -1.3%; P=0.04). Treatment intensification by switching to quadruple oral therapy showed similar glucose-lowering efficacy to weekly GLP-1RA-based triple therapy. Meanwhile, the therapeutic response was affected by C-peptide levels in the GLP-1RA therapy group but not in the quadruple therapy group.

Safety of multiple intravenous infusions of adipose-derived mesenchymal stem cells for hospitalized cases of COVID-19: a randomized controlled trial.

Objective: The purpose of the study was to assess the safety of allogeneic, Hope Biosciences Adipose Derived Mesenchymal Stem Cells (HB-adMSCs) for the treatment of hospitalized subjects with COVID-19. Methods: N = 48 patients were randomly assigned to HB-adMSC (100 MM) or placebo group. Four intravenous infusions of HB-adMSCs or saline were administered at days 0, 3, 7, 10. The primary safety endpoint was incidence of adverse and serious adverse events (AE/SAEs); secondary endpoints were incidence of specific AEs and alterations in hematology, biochemistry, and coagulation parameters. Results: Majority of AEs were mild in severity. HB-adMSC group showed a higher incidence of cardiopulmonary failure, anemia, anxiety, and diarrhea, while placebo group showed a higher incidence of headaches, fatigue, and chest discomfort (posterior probabilities ≥80%). Deaths were attributed to severe complications due to COVID-19 and were unrelated to study drug. No AEs were attributed to the treatment. Hematology and coagulation panel alterations were not associated with HB-adMSCs. Analyses of inflammatory markers showed increased levels of interleukin-6 and C-reactive protein over time in HB-adMSC group (posterior probabilities ≥78%). Conclusion: Multiple infusions of 100MM allogeneic HB-adMSCs were considered safe for the study population. More research is needed to determine the safety of MSC therapy. Clinical trial registration: (www.ClinicalTrials.gov) identifier NCT04362189.

Improvement of osseointegration efficacy of titanium implant through plasma surface treatment.

A novel plasma treatment source for generating cylindrical plasma on the surface of titanium dental implants is developed herein. Using the titanium implant as an electrode and the packaging wall as a dielectric barrier, a dielectric barrier discharge (DBD) plasma was generated, allowing the implant to remain sterile. Numerical and experimental investigations were conducted to determine the optimal discharge conditions for eliminating hydrocarbon impurities, which are known to degrade the bioactivity of the implant. XPS measurement confirmed that plasma treatment reduced the amount of carbon impurities on the implant surface by approximately 60%. Additionally, in vitro experiments demonstrated that the surface treatment significantly improved cell adhesion, proliferation, and differentiation. Collectively, we proposed a plasma treatment source for dental implants that successfully removes carbon impurities and facilitate the osseointegration of SLA implants.

Frequency-dependent effect of intravenous administration of human adipose-derived mesenchymal stem cell therapy for severe Systemic Lupus Erythematosus: A case report.

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that involves abnormal activation of immune response, affecting multiple organs, including joints, kidneys, lungs, skin, and the hematopoietic system, thereby impairing their normal function. Despite there being no cure for SLE, Mesenchymal Stem Cell (MSC) therapy offers hope for SLE patients because of its potent role in immunomodulation. Here, we report a case of a 65-year-old female battling with SLE for almost 30 years and on a treatment regimen consisting of several medications. Given the level of immunosuppression associated with conventional SLE treatments, the subject was initially enrolled as a participant in a study protocol designed to provide immune protection against COVID-19. The subject received multiple infusions of autologous Hope Biosciences adipose-derived MSCs (HB-adMSCs) which significantly improved her SLE symptoms and functionality that led the patient's physician to discontinue her Rituximab regime. Based on her response to HB-adMSC therapy, the subject was approved to receive a set of nine infusion treatments to specifically treat her SLE symptoms. Over the course of ∼ one year, the first six infusions were given on a monthly basis, while the remaining three were administered bimonthly - each with a dose of 200 million HB-adMSCs. Since the beginning of the treatment, the subject showed remarkable improvements in her SLE symptoms, as demonstrated by changes in her SF-36 questionnaire responses, Visual Analog Scale (VAS) scores, and C-Reactive Protein (CRP) measurements; however, worsening of the symptoms was noted later during treatment course (when the frequency of infusions changed to bimonthly). Although the shift in remission-relapse cycle is not fully understood, however, the data suggest that treatment frequency might be the key player. No serious adverse events occurred during the entire treatment period. Further research is needed to evaluate the results of this study.

Safety and efficacy of autologous, adipose-derived mesenchymal stem cells in patients with rheumatoid arthritis: a phase I/IIa, open-label, non-randomized pilot trial.

OBJECTIVE: The present study is a phase I/IIa non-randomized, open-label study to evaluate safety and efficacy of a single, intravenous infusion of autologous, adipose-derived mesenchymal stem cells (adMSCs) over a period of 52 weeks, in patients with active rheumatoid arthritis (RA). METHODS: 15 eligible RA patients aged 18-65 years were enrolled and followed up at weeks 4, 12, 26 and 52 after receiving a single intravenous dose of 2 × 108 adMSCs. Efficacy was examined using American College of Rheumatology (ACR66/68 score) criteria for swollen and tender joint counts (S/TJC), and serum TNF-α, IL-6, CRP, and ESR levels. Safety endpoints included measures of hematologic, hepatic, and renal function. RESULTS: ACR66/68 scores for both S/TJC showed significant improvements with large effect sizes (ES) at week 52 vs baseline (p < 0.01, ES = 0.83 and p < 0.001, ES = 0.93 respectively). Medium to large ES were also obvious for ACR66/68 scores measured at other timepoints. Levels of inflammatory markers, TNF-α, IL-6 and ESR remained unchanged compared to baseline. However, a difference in CRP levels with a small effect size was observed at week 4 (p = 0.229, ES = 0.33) with further improvement at week 52 (p = 0.183, ES = 0.37). Post-intervention, levels of hematologic, hepatic, and renal function remained largely unchanged (p > 0.05). No acute or long-term serious adverse events (AEs) occurred. CONCLUSIONS: The results indicated that a single, intravenous administration of autologous adMSCs is safe and efficacious for improvement in joint function in patients with active RA. Data from the current study supports the exploration of ad-MSCs as a therapeutic intervention for RA. Trial Registration Clinical trial registration number: NCT03691909. Registered September 27, 2018- Retrospectively registered ( https://clinicaltrials.gov/show/NCT03691909 ).

Pattern analysis for prognosis of differentiated thyroid cancer according to preoperative serum thyrotropin levels.

Serum thyrotropin (TSH) level after thyroid surgery affects the prognosis of differentiated thyroid cancer (DTC). However, the effects of preoperative serum TSH levels on the prognosis of DTC remain contradictory. In this study, to better understand the relationship between preoperative TSH levels and the prognosis of DTC, we performed pattern analysis of prognostic factors of DTC according to preoperative serum TSH levels. We retrospectively reviewed the clinical records of patients who were diagnosed and treated for DTC at the Samsung Medical Center, between 1994 and 2016. We reviewed preoperative serum TSH levels and performed a pattern analysis with prognostic risk factors for DTC. For pattern analysis, TSH was divided into 10 groups of equal fractions (TSH decile). We found a linear association between preoperative TSH levels and extra-thyroidal extension and lymph node metastasis. However, primary tumor size and initial distant metastasis showed a bimodal peak, which was similar to the pattern of overall and disease-specific death. We found that preoperative TSH range which showed the lowest mortality rate was about 0.8 to 1.59 mIU/L, which are slightly lower normal TSH levels. Although there was no linear trend, the primary tumor size, initial distant metastasis, and mortality of DTC were closely related with preoperative TSH decile and they showed a bimodal pattern. The results obtained in this study provide additional information for understanding the association between preoperative TSH levels and DTC prognosis.

Influence of flow rate, fluid temperature, and extension line on Hotline and S-line heating capability: an in vitro study.

BACKGROUND: A fluid warmer can prevent hypothermia during the perioperative period. This study evaluated the heating capabilities of Hotline and Barkey S-line under different flow rates and initial fluid temperatures, as well as after the extension line installation. METHODS: We measured the temperature of a 0.9% sodium chloride solution at the fluid warmer outlet (TProx) and the extension line end (TDistal) with three different initial fluid temperatures (room, warm, and cold) and two flow rates (250 ml/hr and 100 mL/hr). RESULTS: At a 250 ml/hr flow rate, the TProx and TDistal values were observed to be higher in Hotline than in S-line when using room-temperature or cold fluid. Administering of the warm fluid at the same flow rate significantly increased the TProx and TDistal values in S-line more than the cold and room-temperature fluids. At flow rates of 100 ml/hr, TDistal values were significantly lower than TProx values in both devices regardless of the initial fluid temperature. CONCLUSIONS: Hotline outperformed S-line for warming fluids at a high flow rate with cold or room-temperature fluids. Administering warm fluid in S-line prevented a decrease in the fluid temperature at a high flow rate. However, at a low flow rate, the fluid temperature significantly decreased in both devices after passing through an extension line.

Glucocorticoid-Induced Hypokalemic Periodic Paralysis after Short-Term Use of Tenofovir with Hypophosphatemia: A Case Report.

Hypokalemic periodic paralysis (HPP) is a neuromuscular disorder associated with muscular dysfunction caused by hypokalemia. There are various causes of HPPs and rarely, HPP appears to be relevant to tenofovir or glucocorticoid treatment. There have been several case reports of tenofovir-related nephrotoxicity or tenofovir-induced HPP. However, a case report of glucocorticoid-induced HPP in a patient using tenofovir temporarily has not been reported. Herein, we report a case of glucocorticoid-induced HPP with short-term use of tenofovir. A 28-year-old man visited the emergency room with decreased muscle power in all extremities (2/5 grade). In their past medical history, the patient was treated with tenofovir for two months for a hepatitis B virus infection. At the time of the visit, the drug had been discontinued for four months. The day before visiting the emergency room, betamethasone was administered at a local clinic for herpes on the lips. Laboratory tests showed hypokalemia, hypophosphatemia, and mild metabolic acidosis. However, urinalysis revealed no abnormal findings. Consequently, it can be postulated that this patient developed HPP by glucocorticoids after taking tenofovir temporarily. This is the first case report of glucocorticoid-induced HPP in a patient using tenofovir. Clinicians who prescribe tenofovir should be aware of HPP occurring when glucocorticoids are used.

Preoperative Serum Calcitonin and Its Correlation with Extent of Lymph Node Metastasis in Medullary Thyroid Carcinoma.

The optimal initial surgical extent for medullary thyroid carcinoma (MTC) remains controversial. Previous studies on serum calcitonin are limited to reporting the calcitonin threshold according to anatomical disease burden. Here, we evaluated whether preoperative calcitonin levels can be used to predict optimal surgical extent. We retrospectively reviewed the 170 patients with MTC at a tertiary Korean hospital from 1994 to 2019. We extracted data on preoperative calcitonin level, primary tumor size and the number and location of lymph node metastases (LNMs). To evaluate disease extent, we divided the patients into five groups: no LNM, central LNM, ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis. We calculated the positive and negative likelihood ratios (LRs) for multiple categories of preoperative calcitonin levels. Preoperative calcitonin level positively correlated with primary tumor size (rho = 0.744, p < 0.001) and LNM number (rho = 0.537, p < 0.001). Preoperative calcitonin thresholds of 20, 200, and 500 pg/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. The negative LRs were 0.1 at a preoperative calcitonin cut-off of 100 pg/mL in the central LNM, 0.18 at a cut-off of 300 pg/mL in the ipsilateral lateral LNM, and 0 at a cut-off of 300 pg/mL in the contralateral lateral LNM. The preoperative calcitonin level correlates with disease extent and has diagnostic value for predicting LNM extent. Our results suggest that the preoperative calcitonin level can be used to determine optimal initial surgical extent.

Preoperative Serum Thyroglobulin and Its Correlation with the Burden and Extent of Differentiated Thyroid Cancer.

Lymph node metastasis (LNM) in differentiated thyroid cancer (DTC) is usually detected with preoperative ultrasonography; however, this has limited sensitivity for small metastases, and there is currently no predictive biomarker that can help to inform the extent of surgery required. We evaluated whether preoperative serum thyroglobulin levels can predict tumor burden and extent. We retrospectively reviewed the clinical records of 4029 DTC cases diagnosed and treated at a Samsung Medical Center between 1994 and 2016. We reviewed primary tumor size, number and location of LNM, and presence of distant metastases to reveal relationships between tumor burden and extent and preoperative serum thyroglobulin levels. We found a linear association between increasing preoperative thyroglobulin levels, the size of the primary tumor, and the number of LNM (r = 0.34, p < 0.001, r = 0.20, p < 0.001, respectively). Tumor extent also increased with each decile of increasing preoperative thyroglobulin level (r = 0.18, p < 0.001). Preoperative thyroglobulin levels of 13.15 ng/mL, 30.05 ng/mL, and 62.9 ng/mL were associated with the presence of ipsilateral lateral LNM, contralateral lateral LNM, and distant metastasis, respectively. Our results suggest that preoperative measurement of serum thyroglobulin may help to predict LNM and help to tailor surgery.

Predictive Performance of Glycated Hemoglobin for Incident Diabetes Compared with Glucose Tolerance Test According to Central Obesity.

BACKGROUND: To examine whether glycated hemoglobin (HbA1c) test would be a suitable screening tool for detecting high-risk subjects for diabetes compared to oral glucose tolerance test (OGTT) according to accompanied central obesity. METHODS: In this prospective population-based cohort study, both OGTT and HbA1c tests were performed and continued every 2 years up to 12 years among individuals with non-diabetic state at baseline (aged 40 to 69 years, n=7,512). Incident diabetes was established by a doctor, HbA1c ≥6.5%, and/or fasting plasma glucose (FPG) ≥126 mg/dL, and/or 2-hour postprandial glucose (2hPG) level based on OGTT ≥200 mg/dL. Discriminative capacities of high HbA1c (≥5.7%) versus high 2hPG (≥140 mg/dL) for predicting incident diabetes were compared using Cox-proportional hazard regression and C-index. RESULTS: During the median 11.5 years of follow-up period, 1,341 (17.6%) developed diabetes corresponding to an incidence of 22.1 per 1,000 person-years. Isolated high 2hPG was associated with higher risk for incident diabetes (hazard ratio [HR], 4.29; 95% confidence interval [CI], 3.56 to 5.17) than isolated high HbA1c (HR, 2.79; 95% CI, 2.40 to 3.26; P<0.05). In addition, high 2hPG provided better discriminatory capacity than high HbA1c (C-index 0.79 vs. 0.75, P<0.05). Meanwhile, in subjects with central obesity, the HR (3.95 [95% CI, 3.01 to 5.18] vs. 2.82 [95% CI, 2.30 to 3.46]) and discriminatory capacity of incident diabetes (C-index 0.75 vs. 0.75) between two subgroups became comparable. CONCLUSION: Even though the overall inferior predictive capacity of HbA1c test than OGTT, HbA1c test might plays a complementary role in identifying high risk for diabetes especially in subjects with central obesity with increased sensitivity.

Improved survival after early detection of asymptomatic distant metastasis in patients with thyroid cancer.

The incidence of thyroid cancer (TC) has been increasing in many countries and concerns about overdiagnosis are also widely shared. However, early detection may be helpful in some high-risk TC patients, such as those with initial distant metastasis. We conducted this study to evaluate the usefulness of early detection in TC patients with initial distant metastasis. We retrospectively reviewed the clinical data of 13,249 TC patients, and found 127 patients with initial distant metastasis. Enrolled patients were divided into two groups according to the diagnostic periods; before and after 2004, when the early detection of TC by ultrasonography began in earnest in Korea. Patients were also divided into two groups according to the presence of symptoms. Prior to 2004, 33 patients (1.7% of TC patients) were diagnosed with TC with initial distant metastasis and 16 (48.5%) of them died. After 2004, 94 patients (0.8% of TC patients) were diagnosed with TC with initial distant metastasis and 29 (30.9%) of them died. Prior to 2004, the disease-specific death rates were similar between the asymptomatic and symptomatic groups (46.2% vs. 50.0%, P = 0.566). Conversely, after 2004, the asymptomatic group showed a significantly lower disease-specific death rate as compared with that of the symptomatic groups (17.2% vs. 60.0%; P < 0.001). Early detection had a significant positive impact on survival outcomes only after 2004, especially in asymptomatic TC patients with initial distant metastasis.

Eighth edition of tumor-node-metastasis staging system improve survival predictability for papillary, but not follicular thyroid carcinoma: A multicenter cohort study.

OBJECTIVES: This study aimed to evaluate the proposed changes in the eighth edition of the tumor-node-metastasis staging system (TNM-8) compared with the seventh edition (TNM-7) in terms of pathologic subtypes, using a large multicenter thyroid cancer cohort. MATERIALS AND METHODS: We retrospectively reviewed 7717 patients with papillary (PTC) and 273 with follicular thyroid carcinoma (FTC) who underwent thyroid surgery between 1996 and 2005. We assessed the proportion of variation explained (PVE) to compare the predictive accuracy of disease-specific survival (DSS). RESULTS: During a median 11.3 years of follow-up, 169 (2%) disease-specific deaths were recorded. In patients with PTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 99.6%, 95.7%, 81.5%, and 54.8%, respectively; the corresponding rates in TNM-7 were 99.6%, 98.4%, 98.4%, and 90.1%, respectively. In patients with FTC, the 10-year DSS rates of stages I, II, III, and IV disease in TNM-8 were 97.2%, 69.8%, 50.0%, and 45.5%, respectively; the corresponding rates in TNM-7 were 98.3%, 90.0%, 92.3%, and 42.1%, respectively. Comparing TNM-7 and TNM-8, the PVE values increased from 3.4% to 4.7% in the PTC group, whereas they decreased from 17.5% to 14.5% in the FTC group. CONCLUSION: Our study suggests that the changes in TNM-8 have improved the clinical usefulness of the TNM staging system in terms of predicting DSS in patients with PTC but not FTC. Further studies to establish a more predictable TNM staging system that focuses on patients with FTC are necessary.

Modification of the eight-edition tumor-node-metastasis staging system with N1b for papillary thyroid carcinoma: A multi-institutional cohort study.

OBJECTIVES: Based on the tumor-node-metastasis staging system, eighth edition (TNM-8), N1b is no longer used as a variable to determine final stage in papillary thyroid carcinoma (PTC). We aimed to evaluate the predictability of a simple modification of the TNM staging with N1b classification in a large multicenter thyroid cancer cohort. MATERIALS AND METHODS: This study included 7717 patients with PTC who underwent thyroid surgery between 1996 and 2005 from six tertiary hospitals. We classified patients with stage II into stage IIA and IIB with modified-TNM: older patients with N1b disease were classified as stage IIB, while remaining patients were classified as stage IIA. RESULTS: The mean age was 46.2 years, and 24% were aged ≥55 years. In older patients, the 10-year disease-specific survival (DSS) rate of N1b disease (86.3%) was approximately 10% lower than that of N1a disease, and patients with N1b had significantly poorer DSS than those with N1a (HR = 3.3, p < 0.001). When the modified-TNM was applied, DSS curves between stage groups significantly differed (p < 0.001), and the relative risk of DSS in stage IIB patients was 2.3 times higher than in stage IIA patients (p < 0.001). The proportion of variation explained value of the modified-TNM was 4.9% and that of the TNM-8 was 4.7%. CONCLUSION: This multicenter study reveals that the presence of lateral lymph node metastasis affects disease mortality in PTC, especially in older patients. The sub-classification of stage II in older patients improves DSS predictability. This simple modification of TNM-8 provides better prognostic information for patients with PTC.

Prognosis of Differentiated Thyroid Carcinoma with Initial Distant Metastasis: A Multicenter Study in Korea.

BACKGROUND: Most patients with differentiated thyroid cancer (DTC) have a favorable prognosis. However, patients with DTC and initial distant metastasis have not been commonly found, and their clinical characteristics have seldom been reported. In this study, we analyzed the clinical features and prognosis of patients with DTC and initial distant metastasis in Korea. METHODS: We retrospectively reviewed the clinical data of 242 patients with DTC and initial distant metastasis treated from 1994 to 2013, collected from five tertiary hospitals in Korea. RESULTS: The patients' median age was 51 years, and 65% were women. They were followed for a median of 7 years. Lung was the most common site of distant metastasis: only lung 149 patients (62%), only bone 49 (20%), other single site one (pleura), and combined sites 43 (40 were lung and bone, two were bone and other site, and one was lung and other site). At the time of diagnosis, 50 patients (21%) had non-radioactive iodine (RAI) avidity. Five-year disease-specific survival (DSS) was 85% and 10-year DSS was 68%, which were better than those in previous studies. After multivariate analysis, old age, male sex, metastatic site, and histologic type (follicular type) were significant factors for poor prognosis. However, negative RAI avidity status was not a significant prognostic factor after adjusting for other variables. CONCLUSION: The prognosis of Korean patients with DTC and initial distant metastasis was better than in previous studies. Old age, male sex, metastasis site, and histologic type were significant prognostic factors.