Three-dimensional culture conditioned bone marrow MSC secretome accelerates wound healing in a burn injury mouse model.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising regenerative therapeutic approach for wound healing. To determine the effects of cultured MSCs as a 2D monolayer (2D-MSCs) and 3D spheroids (3D-MSCs) on their secretomes, and to examine the effect of 3D-MSC secretomes on endothelial cells (ECs) and MSCs in a burn injury mouse model. MSCs were cultured as 2D monolayers (2D-MSCs) and 3D spheroids (3D-MSCs) and their cellular characteristics were evaluated by western blotting. 2D-MSC and 3D-MSC secretomes (condition medium: CM) were analyzed using an angiogenic array. The activation of ECs by 2D-MSC and 3D-MSC CMs was examined in cellular proliferation, migration, and tube formation assays. The wound healing effects of 2D-MSCs and 3D-MSCs were determined in vivo using a burn injury mouse model. 3D culture conditions altered the markers of components that regulate cell survival, cytoskeletal, adhesion, and proliferation. Interleukin-6 (IL-6), vascular endothelial growth factor A (VEGFA), IL-8, and chemokine (CXC motif) ligand 1 (CXCL1) were present at high levels in the CM of 3D-MSCs compared with 2D-MCs. 3D-MSC-CMs promoted the proliferation, migration, and tube formation of ECs. Furthermore, 3D-MSC treatment enhanced wound healing in a burn injury mouse model. 3D culture improves proangiogenic factors in the MSC secretome and 3D-MSCs represent a new cell-based treatment strategy for wound healing.

Current understanding of MSC-derived exosomes in the management of knee osteoarthritis.

Mesenchymal stem cell-derived exosomes (MSC-Exos) have been utilized as medicinal agents or as delivery vehicles in cartilage injuries and cartilage-based diseases. Given the ongoing emergence of evidence on the effector mechanisms and methods of the utility of the MSC-Exos in knee osteoarthritis, a comprehensive review of the current evidence is the need of the hour. Hence, in this article, we review the current understanding of the role of MSC-Exos in the management of knee osteoarthritis in view of their classification, characterization, biogenesis, mechanism of action, pathways involved in their therapeutic action, in-vitro evidence on cartilage regeneration, in-vivo evidence in OA knee models and recent advances in using MSC-Exos to better streamline future research from bench to bedside for OA knee.

Impact of Positron Emission Tomography Viability Imaging: Guided Revascularizations on Clinical Outcomes in Patients With Myocardial Scar on Single-Photon Emission Computed Tomography Scans.

BACKGROUND: Positron emission tomography (PET) viability scan is used to determine whether patients with a myocardial scar on single-photon emission computed tomography (SPECT) may need revascularization. However, the clinical utility of revascularization decision-making guided by PET viability imaging has not been proven yet. The purpose of this study was to investigate the impact of PET to determine revascularization on clinical outcomes. METHODS: Between September 2012 and May 2021, 53 patients (37 males; mean age = 64 ± 11 years) with a myocardial scar on MIBI SPECT who underwent PET viability test were analyzed in this study. The primary outcome was a temporal change in echocardiographic findings. The secondary outcome was all-cause mortality. RESULTS: Viable myocardium was presented by PET imaging in 29 (54.7%) patients. Revascularization was performed in 26 (49.1%) patients, including 18 (34.0%) with percutaneous coronary intervention (PCI) and 8 (15.1%) with coronary artery bypass grafting. There were significant improvements in echocardiographic findings in the revascularization group and the viable myocardium group. All-cause mortality was significantly lower in the revascularization group than in the medical therapy-alone group (19.2% vs. 44.4%, log-rank P = 0.002) irrespective of viable (21.4% vs. 46.7%, log-rank P = 0.025) or non-viable myocardium (16.7% vs. 41.7%, log-rank P = 0.046). All-cause mortality was significantly lower in the PCI group than in the medical therapy-alone group (11.1% vs. 44.4%, log-rank P < 0.001). CONCLUSION: Revascularization improved left ventricular systolic function and survival of patients with a myocardial scar on SPECT scans, irrespective of myocardial viability on PET scans.

Incidence rate and factors associated with the development of secondary cancers after radioiodine therapy in differentiated thyroid cancer: a multicenter retrospective study.

PURPOSE: The objective of this study was to estimate the incidence of secondary cancers and the factors associated with their development among patients who underwent radioiodine therapy (RIT) with differentiated thyroid cancer. METHODS: We retrospectively collected medical records for patients who underwent first RIT between January 1, 2000, and December 31, 2005, from seven tertiary hospitals in South Korea after total thyroidectomy for differentiated thyroid cancer. Cancer incidence and calculated standardized rate ratio were compared with Korean cancer incidence data. The association between the development of secondary cancers and various parameters was analyzed by Cox-proportional hazard regression. RESULTS: A total of 3106 patients were included in this study. Mean age at the time of diagnosis of thyroid cancer was 45.7 ± 13.3 years old, and 2669 (85.9%) patients were female. The follow-up period was 11.9 ± 4.6 (range, 1.2-19.6) years. A total of 183 secondary cancers, which included 162 solid and 21 hematologic cancers, occurred in 173 patients (5.6%). There was no significant difference between solid cancer incidence in our study population who underwent RIT and the overall Korean population, but the incidence of hematologic cancers and total cancer in our study was significantly higher compared with that of the Korean population. A multivariate analysis identified independent prognostic factors for the development of secondary cancer including age at 1st RIT, male, and total cumulative dose over 200 mCi. CONCLUSION: We need to assess the risk benefit for patients who receive over 200 mCi of a total cumulative dose.

Engineered extracellular vesicle mimetics from macrophage promotes hair growth in mice and promotes human hair follicle growth.

Recent studies clearly show that cell-derived extracellular vesicles (EVs, including exosomes) can promote hair growth. However, large-scale production of EVs remains a big hurdle. Recently, extracellular vesicle mimetics (EMs) engineered by extrusion through various membranes are emerging as a complementary approach for large-scale production. In this study, to investigate their ability to induce hair growth, we generated macrophage-engineered EMs (MAC-EMs) that activated the human dermal papilla (DP) cells in vitro. MAC-EMs intradermally injected into the skin of C57BL/6 mice were retained for up to 72 h. Microscopy imaging revealed that MAC-EMs were predominately internalized into hair follicles. The MAC-EMs treatment induced hair regrowth in mice and hair shaft elongation in a human hair follicle, suggesting the potential of MAC-EMs as an alternative to EVs to overcome clinical limitation.

Relationship between Apathy and Subjective Poor Night-time Sleep in de novo, Untreated Parkinson's Disease.

BACKGROUND: Sleep disturbance is one of the most common non-motor symptoms of Parkinson's disease (PD). However, the confounding effects of dopaminergic medication on sleep are a major challenge in understanding the impact of sleep disturbance in PD. We investigated the sleep disturbance and associated clinical features in patients with de novo, untreated PD. METHODS: One-hundred-eight patients with de novo, untreated PD were included. Night sleep disturbance was evaluated using the night sleep subscale of the Scales for Outcomes in Parkinson's Disease (SCOPA-Sleep). Depression, anxiety, and apathy were assessed using the Geriatric Depression Scale (GDS), Beck Anxiety Inventory (BAI), and Apathy Evaluation Scale (AES), respectively. Early perfusion and dopamine transporter imaging of F-18 FP-CIT PET/CT were performed together with statistical parametric mapping analysis. RESULTS: The night sleep SCOPA-Sleep sub-score was correlated with the AES (p = 0.014), BAI (p = 0.014), and GDS (p = 0.023) scores. Patients with poor night sleep were more apathetic (p = 0.013). Additionally, there was increased perfusion in the left posterior cingulate in patients with sleep disturbance and apathy compared to those with sleep disturbance only. CONCLUSIONS: Night sleep disturbance was related to mood disorders, particularly apathy, in patients with de novo, untreated PD.

Extracellular vesicles derived from macrophage promote angiogenesis In vitro and accelerate new vasculature formation In vivo.

BACKGROUND: Ischemia is the partial or complete blockage of blood supply to tissues. Extracellular vesicles (EVs) are emerging as a therapeutic tool for ischemic diseases. Most EV-based ischemia therapies are based on various stem cells. Here, we propose an alternative cell source for the isolation of pro-angiogenic EVs. METHODS: EVs were isolated from a mouse macrophage cell line (Raw 264.7). The characteristic features of the macrophage-derived EVs (MAC-EVs) were assessed using transmission electron microscopy, nanoparticle tracking analysis, and Western blotting (WB) analysis. WB and qRT-PCR were performed to identify the pro-angiogenic VEGF and Wnt3a proteins and microRNAs (miR-210, miR-126, and miR-130a) in the MAC-EVs. In vitro and in vivo Matrigel plug assays were performed to investigate the capacity of the MAC-EVs for tube (blood vessel-like) formation and new blood vessel formation and assessed by histology. RESULTS: The MAC-EVs was positive for ALIX and negative for calnexin, with a round shape and an average size of 189 ± 65.1 nm. WB and qRT-PCR results revealed that VEGF, Wnt3a and miR-130a were more abundant in the MAC-EVs than cells. MAC-EVs treatment resulted in increased endothelial cellular proliferation, migration, and tube formation in vitro. In vivo assay results revealed that MAC-EVs increased the formation of new and larger blood vessels in the Matrigel plug of mice compared to the formation in the control group. CONCLUSION: Our results suggest that MAC-EVs have the potential to induce angiogenesis in vitro and in vivo, could serve as a pro-angiogenic alternative for ischemic diseases.

Brain F-18 FDG and F-18 FP-CIT PET/CT Findings of c.856_860delCTCTA Mutation McLeod Syndrome.

McLeod syndrome is a rare X-linked recessive genetic disorder that is caused by mutations of the XK gene. It is one of the core neuroacanthocytosis syndromes. We report the case of a 67-year-old man who presented to Kyungpook National University Hospital in the Republic of Korea with progressive worsening of generalized chorea and dystonia. He had no recognized family history of neurologic illness. A peripheral blood smear showed increased acanthocytes. His serum creatine kinase levels were 894 U/L. A brain MRI showed atrophy of the bilateral striatal nuclei. An F-18 F-N-(3-fluoropropyl)-2ß-carboxymethoxy-3ß-(4-iodophenyl) nortropane PET/CT showed moderately decreased dopamine transporter uptake in the putamen and severely decreased uptake in the caudate nucleus. An F-18 fludeoxyglucose PET/CT demonstrated markedly decreased metabolism at the caudate nucleus and the putamen. Whole exome sequencing revealed hemizygous pathogenic mutations of the XK gene (c.856_860delCTCTA;p.Leu286TyrfsTer16). We believe that these findings provide useful information regarding the clinical features of individuals with McLeod syndrome.

Clinical Course of Asymptomatic and Mildly Symptomatic Patients with Coronavirus Disease Admitted to Community Treatment Centers, South Korea.

We evaluated the clinical course of asymptomatic and mildly symptomatic patients with laboratory-confirmed coronavirus disease (COVID-19) admitted to community treatment centers (CTCs) for isolation in South Korea. Of 632 patients, 75 (11.9%) had symptoms at admission, 186 (29.4%) were asymptomatic at admission but developed symptoms during their stay, and 371 (58.7%) remained asymptomatic during their entire clinical course. Nineteen (3.0%) patients were transferred to hospitals, but 94.3% (573/613) of the remaining patients were discharged from CTCs upon virologic remission. The mean virologic remission period was 20.1 days (SD + 7.7 days). Nearly 20% of patients remained in the CTCs for 4 weeks after diagnosis. The virologic remission period was longer in symptomatic patients than in asymptomatic patients. In mildly symptomatic patients, the mean duration from symptom onset to virologic remission was 11.7 days (SD + 8.2 days). These data could help in planning for isolation centers and formulating self-isolation guidelines.

PROGNOSTIC VALUE OF LYMPH NODE UPTAKE ON PRETREATMENT F-18 FDG PET/CT IN PATIENTS WITH N1B PAPILLARY THYROID CARCINOMA.

Objective: The aim of this study was to investigate the prognostic value of metabolic characteristics of metastatic lymph node (LN) using pretreatment F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for patients with papillary thyroid carcinoma (PTC) and metastatic lateral LN (N1b). Methods: Ninety-six PTC patients (female:male = 72:24; median age, 44.5 years) with pathologic N1b who underwent pretreatment FDG PET/CT, total thyroidectomy, and radioactive iodine ablation were retrospectively reviewed. To predict responses to initial therapy and recurrence, clinicopathologic factors and metabolic parameters were reviewed, such as sex, age, tumor size, extranodal extension, number and ratio of metastatic LNs, serum thyroglobulin, and maximum standardized uptake value (SUVmax). Results: Among the 96 PTC patients, 81 (84.4%) were classified into the acceptable response (58 excellent; 23 indeterminate) and 15 (15.6%) into the incomplete response (8 biochemical incomplete; 7 structural incomplete) by the 2015 American Thyroid Association management guideline for differentiated thyroid carcinoma. The multivariate analysis showed that SUVmax of N1b (P = .018), pre-ablation stimulated thyroglobulin level (P = .006), and the ratio of metastatic LNs (P = .018) were related to incomplete response. The cutoff value of each variable was determined by receiver operating characteristic analysis. Nine (9.4%) patients experienced recurrences (median follow-up: 50 months). The Kaplan-Meier analysis revealed that SUVmax of N1b (cutoff value: 2.3; P = .025) and ratio of metastatic LNs (cutoff value: 0.218; P = .037) were significant prognostic factors for recurrence. Conclusion: High SUVmax of N1b cervical LN on pretreatment FDG PET/CT could predict incomplete responses to initial therapy and recurrence in patients with N1b PTC. Abbreviations: ATA = American Thyroid Association; DTC = well-differentiated thyroid carcinoma; FDG = F-18 fluorodeoxyglucose; IQR = interquartile range; LN = lymph node; N1b = metastatic lateral cervical lymph node; PET/CT = positron emission tomography/computed tomography; PTC = papillary thyroid carcinoma; RAI = radioactive iodine; ROC = receiver operating characteristic; SUVmax = maximum standardized uptake value; Tg = thyroglobulin; USG = ultrasonography.

Can calcified pulmonary metastases detected by (18)F-FDG PET/CT suggest the primary tumor?

Many calcified nodules are encountered on the (18)F-FDG PET/CT scan and even though most of them are benign, the possibility of calcified pulmonary metastases (CPM) should be considered. The CT portion can often differentiate benign diseases due to their morphology. Measuring SUVmax is very important. Understanding the mechanism of calcification in malignant metastatic pulmonary lesions may be useful to suggest their origin.

Prediction for recurrence using F-18 FDG PET/CT in pathologic N0 lung adenocarcinoma after curative surgery.

BACKGROUND: The aim of this study was to investigate risk factors for recurrence in patients with lung adenocarcinoma (LAD) who were pathologically N0 (pN0) after curative surgical resection. METHODS: A total of 102 LAD patients (M/F = 55/47, mean age, 62.6 ± 9.4 years) diagnosed as pN0 after curative surgery were included in this study. Clinical, biochemical, radiologic, and pathologic findings were reviewed and analyzed for recurrence. Metabolic parameters [SUVmax, metabolic tumor volume (MTV), total lesion glycolysis (TLG)] on pretreatment F-18 FDG PET/CT were also obtained and analyzed for recurrence. RESULTS: Of 102 patients, 38 (37.3%) were found to experience recurrence for 33.6 ± 16.3 months. SUVmax, MTV, and TLG were significantly higher in patients with recurrence. The optimal cutoff values determined using a receiver-operating characteristic curve were 6.90 for SUVmax, 10.78 cm(3) for MTV, and 39.68 for TLG. Univariate analysis showed that tumor size, tumor marker, SUVmax, MTV, and TLG were prognostic factors for recurrence. In multivariate analyses, after adjusting for age, sex, tumor size, pathologic T stage, and tumor marker, high SUVmax, MTV, and TLG showed an association with an increased risk of recurrence. CONCLUSIONS: Metabolic parameters on pretreatment F-18 FDG PET/CT can predict recurrence in pN0 LAD patients who underwent curative surgery. Therefore, patients with high metabolic parameters on PET can be considered as candidates for adjuvant therapy to reduce recurrence and should be monitored carefully for early detection of possible recurrence.

Metabolic parameters using ¹8F-FDG PET/CT correlate with occult lymph node metastasis in squamous cell lung carcinoma.

PURPOSE: The aim of this study was to investigate predictability of occult lymph node metastasis (OLM) using metabolic parameters on pretreatment (18)F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET)/CT in squamous cell non-small cell lung carcinoma (SC-NSCLC) patients who were clinically node negative (cN0) before surgery. METHODS: A total of 63 cN0 SC-NSCLC patients (M/F = 61/2, mean age 64.1 ± 8.0) who underwent curative surgery with lymph node dissection were enrolled in this study. Metabolic tumor volume (MTV) of the primary tumor was obtained with a standardized uptake value (SUV) threshold of 2.5. Total lesion glycolysis (TLG) was calculated by multiplication of the MTV and its SUVmean. Metabolic parameters (SUVmax, MTV, and TLG) and clinicopathological factors were analyzed for OLM. RESULTS: Of 63 patients, 12 (19.0 %) had OLM. Significantly higher SUVmax, MTV, TLG, and pathological tumor size were observed in patients with OLM. The optimal cutoff values for prediction of OLM determined using a receiver-operating characteristic (ROC) curve were 8.8 for SUVmax, 18.9 cm(3) for MTV, 88.4 for TLG, and 2.8 cm for pathological tumor size. Univariate analysis showed correlation of SUVmax, MTV, and TLG with the rate of OLM. In multivariate analyses, high SUVmax and MTV showed an association with an increased risk of OLM, after adjusting for age, sex, pathological tumor size, T stage, and location. CONCLUSION: Metabolic parameters on pretreatment (18)F-FDG PET/CT were significant predictors for OLM in cN0 SC-NSCLC patients. Surgical planning can be tailored based on the parameters in order to reduce the risk of hidden residual lymph node metastases in patients.

Prognostic implication of intratumoral metabolic heterogeneity in invasive ductal carcinoma of the breast.

BACKGROUND: The purpose of this study was to evaluate the prognostic implication of findings of intratumoral metabolic heterogeneity on pretreatment (18)F-FDG PET/CT scans in patients with invasive ductal carcinoma (IDC) of the breast. METHODS: One hundred and twenty-three female IDC patients who underwent pretreatment 18F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) scans were retrospectively evaluated in this study. The heterogeneity factor (HF) defined as the derivative (dV/dT) of a volume threshold function from 40% to 80%, was computed for each primary tumor. Other metabolic PET parameters (maximum standardized uptake value [SUVmax], metabolic tumor volume [MTV], and total lesion glycolysis [TLG]) were measured. The HF was compared with clinicopathologic factors and other PET parameters. Univariate and multivariate analyses for the overall survival (OS) were performed. RESULTS: The HF ranged from 0.02 to 6.72 (mean, 0.35 ± 0.82) and significantly correlated with MTV (r = 0.955; p < 0.0001) and TLG (r = 0.354; p = 0.0001). The HF was significantly higher (implying more heterogeneity) in tumors with higher T and N stages. The optimal cut-off values for the OS determined using a receiver operating characteristic (ROC) curve were 0.34 for the HF, 5.6 for SUVmax, 8.55 cm(3) for MTV, and 14.43 for TLG. The OS rate among the 123 patients was 86.2%. T stage (1, 2 vs. 3, 4), N stage (0, 1 vs. 2, 3), M stage (0 vs. 1), ER status (+ vs. -), SUVmax (≤ 5.6 vs. > 5.6), MTV (≤ 8.55 cm(3) vs. > 8.55 cm(3)), TLG (≤ 14.43 vs. > 14.43), and HF (< 0.34 vs. ≥ 0.34) affected the OS on univariate analysis. After adjustment for the effects of TNM stage and ER status, the HF and MTV were significant predictors of OS. Among the PET parameters, the best prognostic factor for OS was the HF. CONCLUSIONS: Intratumoral metabolic heterogeneity correlated closely with the MTV and significantly affected the OS in IDC patients. The HF may act as a robust surrogate marker for the prediction of OS in IDC patients.

Clinical Values of Whole-Body Blood Pool Scans and SPECT for Evaluation of Congenital Vascular Malformation.

Purpose: This study examines the diagnostic potential of whole-body blood pool scintigraphy (WBBPS) using technetium-99 m-labeled red blood cells to detect congenital vascular malformations (CVMs). It aims to compare its efficacy with traditional imaging techniques such as magnetic resonance imaging (MRI) and ultrasonography (USG), emphasizing its potential advantages in terms of characterization of lesions and capacity for whole-body assessment. Methods: The efficacy of WBBPS and single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging in diagnosing CVMs, comparing them with USG and MRI results, was evaluated in this retrospective study. Of the 38 patients, 21 were evaluated using these diagnostic methods, with CVMs classified according to the International Society for the Study of Vascular Anomalies guidelines. Also, this study aimed to elucidate the characteristics between WBBPS, SPECT/CT, USG, or MRI findings and their consistency with the final diagnosis. Results: A total of 21 participants were included in this study, with an average age of 17.7 years old, with female predominance (57.1%). The most common diagnosis was vascular malformations (VMs) (71.4%), followed by combined vascular malformations (14.3%) and lymphatic malformations (9.5%). WBBPS demonstrated positive results in 95.2% of cases. Distinct imaging patterns for each condition were observed, with WBBPS being crucial in locating lesions. Conclusion: The study findings suggested that WBBPS with SPECT/CT could be helpful in detecting occult VM lesions and ruling out a lymphatic malformation diagnosis. Thus, it can be employed in the evaluation of CVMs.

Clinical Implications of Adding SPECT/CT to Radioiodine Whole-Body Scan in Patients With Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis.

PURPOSE: This study aimed to determine the usefulness of adding SPECT/CT to radioiodine whole-body scans (WBSs) for the treatment of differentiated thyroid cancer (DTC). PATIENTS AND METHODS: A systematic review and meta-analysis were performed following the PRISMA guidelines (PROSPERO registration: CRD42022341732) to compare the feasibility of conclusive readings and the frequency of changes in treatment plans in patients with DTC undergoing WBS + SPECT/CT versus WBS. MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles concerning thyroid cancer, radioactive iodine, and SPECT/CT or SPECT, published before August 16, 2023. Studies not comparing WBS + SPECT/CT with WBS, those lacking target outcomes, and those not involving human subjects were excluded. The risk of bias was assessed using the RoBANS 2.0 (Risk of Bias Assessment Tool for Nonrandomized Studies) tool. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system was used to evaluate the quality of evidence and strength of recommendations. RESULTS: A total of 30 studies (prospective n = 9, retrospective n = 21) were included in the meta-analyses. Adding SPECT/CT to WBS was shown to increase conclusive readings for cervical lesions, extracervical lesions, and all regions. Lesion-based analyses showed improvements of 14%, 20%, and 18%, respectively, whereas scan-based analyses showed improvements of 27%, 9%, and 34%. The addition of SPECT/CT to WBS led to changes in 30% of treatment plans after diagnostic scans and 9% of treatment plans after posttherapeutic scans. The quality of evidence and strength of recommendations were low. CONCLUSIONS: Compelling evidence demonstrates that the addition of SPECT/CT to WBS improves lesion localization, diagnostic performance, and therapy plan for patients with DTC.

Smart Nanoscale Extracellular Vesicles in the Brain: Unveiling their Biology, Diagnostic Potential, and Therapeutic Applications.

Information exchange is essential for the brain, where it communicates the physiological and pathological signals to the periphery and vice versa. Extracellular vesicles (EVs) are a heterogeneous group of membrane-bound cellular informants actively transferring informative calls to and from the brain via lipids, proteins, and nucleic acid cargos. In recent years, EVs have also been widely used to understand brain function, given their "cell-like" properties. On the one hand, the presence of neuron and astrocyte-derived EVs in biological fluids have been exploited as biomarkers to understand the mechanisms and progression of multiple neurological disorders; on the other, EVs have been used in designing targeted therapies due to their potential to cross the blood-brain-barrier (BBB). Despite the expanding literature on EVs in the context of central nervous system (CNS) physiology and related disorders, a comprehensive compilation of the existing knowledge still needs to be made available. In the current review, we provide a detailed insight into the multifaceted role of brain-derived extracellular vesicles (BDEVs) in the intricate regulation of brain physiology. Our focus extends to the significance of these EVs in a spectrum of disorders, including brain tumors, neurodegenerative conditions, neuropsychiatric diseases, autoimmune disorders, and others. Throughout the review, parallels are drawn for using EVs as biomarkers for various disorders, evaluating their utility in early detection and monitoring. Additionally, we discuss the promising prospects of utilizing EVs in targeted therapy while acknowledging the existing limitations and challenges associated with their applications in clinical scenarios. A foundational comprehension of the current state-of-the-art in EV research is essential for informing the design of future studies.

Efficacy of Empirical 131 I Radioiodine Therapy in Well-Differentiated Thyroid Carcinoma Patients With Thyroglobulin-Elevated Negative Iodine Scintigraphy Syndrome : A Systematic Review and Meta-analysis.

OBJECTIVES: This study aimed to perform a systematic review and meta-analysis on the efficacy of empirical high-dose radioiodine therapy in treating differentiated thyroid cancer patients with thyroglobulin (Tg)-elevated negative iodine scintigraphy (TENIS) syndrome. METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify relevant studies published until April 2022. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist and registered in an international prospective register of systematic reviews (PROSPERO). Meta-analyses of proportions and odds ratios were performed to assess the beneficial effect of empirical high-dose radioiodine therapy in patients with TENIS syndrome. Subgroup analysis was also performed according to the presence of micrometastasis or macrometastasis. RESULTS: We identified 14 studies including 690 patients who received empirical high-dose radioiodine therapy for TENIS syndrome. Those who had micrometastasis exhibited additional lesions not previously observed on diagnostic whole-body scan (prop = 0.64, 95% confidence interval [CI], 0.51-0.77) and had reduced serum Tg levels (prop = 0.69; 95% CI, 0.52-0.84) after empirical radioiodine treatment. No such findings were observed among patients with macrometastasis. Moreover, we found that the empirical radioiodine treatment group had lower serum Tg levels than did controls (odds ratio = 0.27; 95% CI, 0.09-0.87), which suggests a lower risk of disease progression. CONCLUSIONS: Our findings indicate that empirical high-dose radioiodine therapy promoted beneficial effects and could be recommended for patients with TENIS syndrome, especially those with micrometastasis.

Comparison of Recombinant Human Thyroid-Stimulating Hormone and Thyroid Hormone Withdrawal for 131 I Therapy in Patients With Intermediate- to High-Risk Thyroid Cancer : A Systematic Review and Meta-analysis.

BACKGROUND: This meta-analysis and systematic review aimed to evaluate the therapeutic efficacy and advantages associated with the use of recombinant human thyroid-stimulating hormone (rhTSH) for radioactive iodine (RAI) therapy in patients with intermediate- to high-risk differentiated thyroid cancer. PATIENTS AND METHODS: MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant articles reporting clinical outcomes of rhTSH compared with thyroid hormone withdrawal (THW) in patients with intermediate- to high-risk differentiated thyroid cancer published between January 2012 and June 2023. Meta-analyses were performed (PROSPERO registration number: CRD42022340915) to assess the success rate of radioiodine remnant ablation (RRA) in patients with intermediate to high risk and determine the disease control rate among patients with distant metastases, evaluated using the RECIST criteria. RESULTS: Thirteen studies involving 1858 patients were included in the meta-analysis. Pooled analyses revealed significantly higher overall RRA success rate in the rhTSH group compared with the THW group, with a risk ratio (RR) of 1.12 (95% confidence interval [CI], 1.01-1.25). However, in the subgroup analysis of high-risk patients, pooled analyses showed no significant differences in RRA success rate between the rhTSH group compared with the THW group with a pooled RR of 1.05 (95% CI, 0.88-1.24). In patients with distant metastases, there were no significant differences in the disease control rate between groups, with a pooled RR of 1.06 (95% CI, 0.78-1.44). CONCLUSIONS: rhTSH for RAI therapy is a practical option for RAI therapy in patients with intermediate- to high-risk thyroid cancer, including those with distant metastases.

Predictive factors for severe radiation-induced lung injury in patients with lung cancer and coexisting interstitial lung disease.

BACKGROUND AND PURPOSE: This study aimed to investigate the predictive factors of severe radiation-induced lung injury (RILI) in patients with lung cancer and coexisting interstitial lung disease (ILD) undergoing conventionally fractionated thoracic radiotherapy. MATERIALS AND METHODS: The study includes consecutive patients treated with thoracic radiotherapy for lung cancer at two tertiary centers between 2010 and 2021. RILI severity was graded using the National Cancer Institute Common Terminology Criteria version 5.0, with severe RILI defined as toxicity grade ≥4, and symptomatic RILI as grade ≥2. The absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and C-reactive protein were collected within 4 weeks before starting radiotherapy. Neutrophil-lymphocyte ratios (NLR) were calculated as ANC/ALC. The median follow-up was 9 (range, 6-114) months. RESULTS: Among 54 patients, 22 (40.7 %) had severe RILI. On multivariate logistic regression analysis, high pretreatment ANC (p = 0.030, OR = 4.313), pretreatment NLR (p = 0.007, OR = 5.784), and ILD severity (p = 0.027, OR = 2.416) were significant predictors of severe RILI. Dosimetric factors were not associated with severe RP. Overall survival was significantly worse for patients with severe RILI than those without, with 1-year cumulative overall survival rates of 7.4 % and 62.8 %, respectively. CONCLUSION: Pretreatment blood NLR, ANC, and ILD severity were associated with severe RILI. Overall survival was dismal for patients with severe RILI.