Distinct effects of rosuvastatin and rosuvastatin/ezetimibe on senescence markers of CD8+ T cells in patients with type 2 diabetes mellitus: a randomized controlled trial.

Objectives: Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to ß-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers. Methods: In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication. Results: The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (Treg) significantly decreased after intervention in the rosuvastatin/ezetimibe group (-4.5 ± 14.1% and -1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p=0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p=0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c (p=0.314) or LDL-C (p=0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group (p=0.011), but not in the rosuvastatin group (p=0.339). Conclusions: We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels.

Feasibility of active surveillance in patients with clinically T1b papillary thyroid carcinoma ≤1.5 cm in preoperative ultrasonography: MASTER study.

Objective: Active surveillance (AS) is generally accepted as an alternative to immediate surgery for papillary thyroid carcinoma (PTC) measuring ≤1.0 cm (cT1a) without risk factors. This study investigated the clinicopathologic characteristics of PTCs measuring ≤2.0 cm without cervical lymph node metastasis (cT1N0) by tumor size group to assess the feasibility of AS for PTCs between 1.0 cm and 1.5 cm (cT1b≤1.5). Design: This study enrolled clinically T1N0 patients with preoperative ultrasonography information (n= 935) from a cohort of 1259 patients who underwent lobectomy and were finally diagnosed with PTC from June 2020 to March 2022. Results: The cT1b≤1.5 group (n = 171; 18.3 %) exhibited more lymphatic invasion and occult central lymph node (LN) metastasis with a higher metastatic LN ratio than the cT1a group (n = 719; 76.9 %). However, among patients aged 55 years or older, there were no significant differences in occult central LN metastasis and metastatic LN ratio between the cT1a, cT1b≤1.5, and cT1b>1.5 groups. Multivariate regression analyses revealed that occult central LN metastasis was associated with age, sex, tumor size, extrathyroidal extension, and lymphatic invasion in patients under 55, while in those aged 55 or older, it was associated only with age and lymphatic invasion. Conclusion: For PTC patients aged 55 years or older with cT1b≤1.5, AS could be a viable option due to the absence of a significant relationship between tumor size and occult central LN.

Response Prediction of Altered Thyroglobulin Levels After Radioactive Iodine Therapy Aided by Recombinant Human Thyrotropin in Patients with Differentiated Thyroid Cancer.

PURPOSE: Thyroglobulin (Tg) may be released from damaged residual thyroid tissues after radioactive iodine (RAI) therapy in patients with differentiated thyroid carcinoma (DTC). We investigated whether altered levels of serum Tg after recombinant human thyrotropin (rhTSH)-aided RAI therapy could be a prognostic marker in patients with DTC. METHODS: We evaluated 68 patients who underwent RAI therapy after total thyroidectomy. Serum Tg levels were measured just before RAI administration (D0Tg) and 7 days after RAI therapy (D7Tg). Patients with a D0Tg level greater than 2.0 ng/mL were excluded to more precisely evaluate the injury effect of RAI in small remnant tissues. The ratioTg was defined as the D7Tg level divided by that on D0Tg. The therapeutic responses were classified as acceptable or non-acceptable. Finally, we investigated which clinicopathologic parameters were associated with therapeutic response. RESULTS: At the follow-up examination, an acceptable response was observed in 50 patients (73.5%). Univariate analysis revealed significant differences in N stage (P = 0.003) and ratioTg (acceptable vs. non-acceptable responses, 21.9 ± 33.6 vs. 3.8 ± 6.5; P = 0.006). In multivariate analysis, only ratioTg significantly predicted an acceptable response (odds ratio 1.104; 95% confidence interval 1.005-1.213; P = 0.040). A ratioTg above 3.5 predicted an acceptable response with a sensitivity of 66.0%, specificity of 83.3%, and accuracy of 70.6% (area under the curve = 0.718; P = 0.006). CONCLUSIONS: Altered levels of serum Tg after RAI therapy, calculated as the ratioTg (D7Tg/D0Tg), significantly predicted an acceptable response in patients with DTC.

Clinical values of left ventricular mechanical dyssynchrony assessment by gated myocardial perfusion SPECT in patients with acute myocardial infarction and multivessel disease.

PURPOSE: The aim of this study was to evaluate the prognostic value of additional evaluation of left ventricular mechanical dyssynchrony (LVMD) by gated myocardial perfusion single-photon emission computed tomography (GMPS) in patients with acute myocardial infarction (MI) and multivessel disease. METHODS: One hundred and nine acute MI patients with >50 % stenosis in at least one non-culprit artery who underwent GMPS within 2 weeks were enrolled. All patients underwent successful revascularization of the culprit arteries. Those with previous MI, atrial fibrillation, or frequent ventricular premature complexes, cardiac devices, significant patient motion, or procedure-related events were excluded. Phase standard deviation (PSD) and phase histogram bandwidth (PBW) were measured for assessment of LVMD. Patients were followed up for a median of 26 months after index MI, for composite major adverse cardiac events (MACE), which consisted with all-cause death, unplanned hospitalization due to heart failure and severe ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation). Independent predictors of MACE were evaluated. RESULTS: MACE occurred in 22 patients (20 %). Stress PSD (53.3 ± 17.3° vs. 35.3 ± 18.9°; p <0.001), stress PBW (147.6 ± 54.6° vs. 96.8 ± 59.2°; p = 0.001) and resting PBW (126.8 ± 37.5° vs. 96.6 ± 48.9°; p = 0.001) were significantly higher in patients with MACE compared to those without. Multivariate analysis revealed that stress PSD ≥45.5° and stress PBW ≥126.0° were predictive of MACE, as well as suboptimal non-culprit artery revascularization (SNR) and renin-angiotensin system (RAS) blockade medication. Higher stress PSD and stress PBW were associated with poorer prognosis both in patients with and without SNR, and those with RAS blockade medication, but not in those without RAS blockade medication. CONCLUSIONS: LVMD measured by GMPS showed added prognostic value in acute MI with multivessel disease. GMPS could serve as a comprehensive evaluation imaging tool in patients with acute MI and multivessel disease.

Prediction of coronary artery calcium progression by FDG uptake of large arteries in asymptomatic individuals.

PURPOSE: The purpose of this study is to evaluate whether fluorodeoxyglucose (FDG) uptake of the large arteries can predict coronary artery calcium (CAC) progression in asymptomatic individuals. METHODS: Ninety-six asymptomatic individuals who underwent FDG positron emission tomography (PET) and CAC scoring on the same day for health screening and follow-up CAC scoring ≥1 year after baseline studies (mean 4.3 years) were included. Vascular FDG uptake was measured and corrected for blood pool activity to obtain peak and average target-to-blood pool ratios (TBRpeak and TBRavg, respectively) for the carotid arteries, and ascending and abdominal aorta. CAC scores at baseline and follow-up of each individual were measured and absolute CAC change (ΔCAC), annual CAC change (ΔCAC/year), and annual CAC change rate (ΔCAC%/year) were calculated. CAC progression was defined as ΔCAC >0 for individuals with negative baseline CAC; ΔCAC/year ≥10 for those with baseline CAC of 0

Iodine Uptake Patterns on Post-ablation Whole Body Scans are Related to Elevated Serum Thyroglobulin Levels After Radioactive Iodine Therapy in Patients with Papillary Thyroid Carcinoma.

PURPOSE: Serum thyroglobulin (Tg) level is frequently elevated shortly after radioactive iodine (RAI) ablation therapy. The authors studied the relationship between the elevation of serum Tg after RAI therapy and iodine uptake pattern on post-ablation whole body scans (RxWBSs) in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: The study subjects were patients with PTC that had undergone first RAI therapy with thyroid hormone withdrawal after total thyroidectomy. Patients with a high level of serum anti-Tg antibody (TgAb, ≥ 60 U/mL), possible regional or distant metastasis as determined by pre-ablation or post-ablation studies, and negative iodine uptake of the anterior neck on RxWBS were excluded. Serum Tg was checked twice, that is, 7 days after (post-ablation Tg) and on the day of RAI therapy (pre-ablation Tg). Ratio of pre-ablation Tg to post-ablation Tg (Tg ratio) was used to assess changes in serum Tg levels after RAI therapy. Patients were classified into two groups according to the presence of midline uptake above the thyroidectomy bed on RxWBS (negative (group 1) or positive (group 2) midline uptake). Variables were subjected to analysis to identify differences between the two groups. RESULTS: Two hundred and fifty patients were enrolled in this study; 101 in group 1 and 149 in group 2. Based on univariate analysis, post-ablation Tg (8.12 ± 11.05 vs. 34.12 ± 54.31; P < 0.001) and Tg ratio (7.81 ± 8.98 vs. 20.01 ± 19.84; P < 0.001) were significantly higher in group 2. On the other hand, gender, tumor (T) stage, lymph node (N) stage, size, multiplicity or bilaterality of primary tumor, dose of 131I, serum TgAb and thyroid-stimulating hormone (TSH) level (before or after RAI therapy) were not significantly different in the two groups. Variables with P values of < 0.25 by univariate analysis were subjected to multivariate analysis, which showed post-ablation Tg (OR 1.060, 95 % CI = 1.028-1.092; P < 0.001) and Tg ratio (OR 1.059, 95 % CI = 1.028-1.092; P = 0.001) were significantly higher in group 2. CONCLUSION: Serum Tg level after RAI therapy was significantly higher in patients with midline uptake on RxWBS, compared with patients without midline uptake on RxWBS. Further investigations are needed to reveal the correlation between serum Tg elevation and clinical outcome according to the presence of midline uptake.

Usefulness of 3-dimensional stereotactic surface projection FDG PET images for the diagnosis of dementia.

To compare diagnostic performance and confidence of a standard visual reading and combined 3-dimensional stereotactic surface projection (3D-SSP) results to discriminate between Alzheimer disease (AD)/mild cognitive impairment (MCI), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).[F]fluorodeoxyglucose (FDG) PET brain images were obtained from 120 patients (64 AD/MCI, 38 DLB, and 18 FTD) who were clinically confirmed over 2 years follow-up. Three nuclear medicine physicians performed the diagnosis and rated diagnostic confidence twice; once by standard visual methods, and once by adding of 3D-SSP. Diagnostic performance and confidence were compared between the 2 methods.3D-SSP showed higher sensitivity, specificity, accuracy, positive, and negative predictive values to discriminate different types of dementia compared with the visual method alone, except for AD/MCI specificity and FTD sensitivity. Correction of misdiagnosis after adding 3D-SSP images was greatest for AD/MCI (56%), followed by DLB (13%) and FTD (11%). Diagnostic confidence also increased in DLB (visual: 3.2; 3D-SSP: 4.1; P < 0.001), followed by AD/MCI (visual: 3.1; 3D-SSP: 3.8; P = 0.002) and FTD (visual: 3.5; 3D-SSP: 4.2; P = 0.022). Overall, 154/360 (43%) cases had a corrected misdiagnosis or improved diagnostic confidence for the correct diagnosis.The addition of 3D-SSP images to visual analysis helped to discriminate different types of dementia in FDG PET scans, by correcting misdiagnoses and enhancing diagnostic confidence in the correct diagnosis. Improvement of diagnostic accuracy and confidence by 3D-SSP images might help to determine the cause of dementia and appropriate treatment.

Open-Mouth Bone Scintigraphy Is Better than Closed-Mouth Bone Scintigraphy in the Diagnosis of Temporomandibular Osteoarthritis.

PURPOSE: Closed-mouth bone scintigraphy (CM scan) and closed-mouth single-photon emission computed tomography (CM SPECT) are used for conventional evaluation of osteoarthritis of the temporomandibular joint (TMJ). However, the adequacy of open-mouth bone scintigraphy (OM scan) has not yet been evaluated. Therefore, the purpose of this study was to compare the diagnostic performance of CM scan, CM SPECT, and OM scan. METHODS: Thirty-six patients with suspicion of an abnormality of the TMJ and who underwent a (99m)Tc-HDP CM scan, CM SPECT, and an OM scan were enrolled. The scans were assessed visually for the presence of positive focal uptake in the TMJ. Osteoarthritis was defined as arthralgia plus crepitus or radiologic signs of arthrosis. RESULTS: Of 72 TMJs, 21 (29.2 %) were diagnosed with osteoarthritis. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 90.5 %, 49.0 %, 42.2 %, 92.6 % and 61.1 % for the CM scan, 81.0 %, 58.8 %, 44.7 %, 88.2 % and 65.3 % for CM SPECT, and 81.0 %, 82.4 %, 65.4 %, 91.3 % and 81.9 % for the OM scan, respectively. The accuracy of the OM scan was higher than that of CM SPECT and the CM scans (p = 0.004 and p < 0.001, respectively). CONCLUSIONS: The OM scan was more accurate than the conventional CM scan and even CM SPECT for diagnosing TMJ osteoarthritis.