TAT38 and TAT38 mimics potently inhibit adipogenesis by repressing C/EBPα, PPARγ, Pi-PPARγ, and SREBP1 expression.

Antiretroviral therapy-naive people living with HIV possess less fat than people without HIV. Previously, we found that HIV-1 transactivator of transcription (TAT) decreases fat in ob/ob mice. The TAT38 (a.a. 20-57) is important in the inhibition of adipogenesis and contains three functional domains: Cys-ZF domain (a.a. 20-35 TACTNCYCAKCCFQVC), core-domain (a.a. 36-46, FITKALGISYG), and protein transduction domain (PTD)(a.a. 47-57, RAKRRQRRR). Interestingly, the TAT38 region interacts with the Cyclin T1 of the P-TEFb complex, of which expression increases during adipogenesis. The X-ray crystallographic structure of the complex showed that the Cys-ZF and the core domain bind to the Cyclin T1 via hydrophobic interactions. To prepare TAT38 mimics with structural and functional similarities to TAT38, we replaced the core domain with a hydrophobic aliphatic amino acid (from carbon numbers 5 to 8). The TAT38 mimics with 6-hexanoic amino acid (TAT38 Ahx (C6)) and 7-heptanoic amino acid (TAT38 Ahp (C7)) inhibited adipogenesis of 3T3-L1 potently, reduced cellular triglyceride content, and decreased body weight of diet-induced obese (DIO) mice by 10.4-11 % in two weeks. The TAT38 and the TAT38 mimics potently repressed the adipogenic transcription factors genes, C/EBPα, PPARγ, and SREBP1. Also, they inhibit the phosphorylation of PPARγ. The TAT peptides may be promising candidates for development into a drug against obesity or diabetes.

FDG PET/CT Maximum Tumor Dissemination to Predict Recurrence in Patients with Diffuse Large B‑Cell Lymphoma / 대한핵의학회잡지

Purpose@#We investigated the prognostic value of maximum tumor dissemination (Dmax), the distance between malignant lesions that were farthest apart, as assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and other clinical factors in patients with diffuse large B-cell lymphoma (DLBCL).We investigated the prognostic value of maximum tumor dissemination (Dmax), the distance between malignant lesions that were farthest apart, as assessed by fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and other clinical factors in patients with diffuse large B-cell lymphoma (DLBCL). @*Methods@#Patients who underwent FDG PET/CT for initial staging and treatment response evaluation of DLBCL were reviewed retrospectively. Baseline Dmax, maximum standardized uptake value, total summation of all metabolic tumor volumes (tMTV), and total summation of all total lesion glycolysis (tTLG) were measured. The treatment response was evaluated at the interim and end of first-line treatment (EOT) using the Deauville score (DS). FDG PET/CT parameters and other clinical factors including sex, age, serum lactate dehydrogenase (LDH) level, stage, performance status, and the International Prognostic Index (IPI) were analyzed to identify factors prognostic of the time to progression (TTP) and disease-specific survival (DSS). @*Results@#A total of 63 patients were included. Univariate survival analysis identified Dmax (> 275 mm), tMTV (> 180 mL), tTLG (> 1300), interim DS (≥ 4), and EOT DS (≥ 4) as significant predictors of poor TTP. Serum LDH level (> 640 IU/L), IPI (≥ 4), tMTV (> 180 mL), tTLG (> 1300), interim DS (≥ 4), and EOT DS (≥ 4) were significant predictors of DSS. After multivariate survival analysis, Dmax (P = 0.008) and EOT DS (P = 0.005) were independent predictors of TTP. EOT DS was an independent predictor of DSS (P = 0.029). @*Conclusions@#Dmax at the time of diagnosis and the EOT response assessed by FDG PET/CT provide useful prognostic information additive to the IPI in patients with DLBCL.

Integrin/TGF-Beta1 inhibitor GLPG-0187 blocks SARS-CoV-2 Delta and Omicron pseudovirus infection of airway epithelial cells which could attenuate disease severity

As COVID-19 continues to pose major risk for vulnerable populations including the elderly, immunocompromised, patients with cancer, and those with contraindications to vaccination, novel treatment strategies are urgently needed. SARS-CoV-2 infects target cells via RGD-binding integrins either independently or as a co-receptor with surface receptor angiotensin-converting enzyme 2 (ACE2). We used pan-integrin inhibitor GLPG-0187 to demonstrate blockade of SARS-CoV-2 pseudovirus infection of target cells. Omicron pseudovirus infected normal human small airway epithelial (HSAE) cells significantly less than D614G or Delta variant pseudovirus, and GLPG-0187 effectively blocked SARS-CoV-2 pseudovirus infection in a dose-dependent manner across multiple viral variants. GLPG-0187 inhibited Omicron and Delta pseudovirus infection of HSAE cells more significantly than other variants. Pre-treatment of HSAE cells with MEK inhibitor (MEKi) VS-6766 enhanced inhibition of pseudovirus infection by GLPG-0187. Because integrins activate TGF-{beta} signaling, we compared plasma levels of active and total TGF-{beta} in COVID-19+ patients. Plasma TGF-{beta}1 levels correlated with age, race, and number of medications upon presentation with COVID-19, but not with sex. Total plasma TGF-{beta}1 levels correlated with activated TGF-{beta}1 levels. In our preclinical studies, Omicron infects lower airway lung cells less efficiently than other COVID-19 variants. Moreover, inhibition of integrin signaling prevents SARS-CoV-2 Delta and Omicron pseudovirus infectivity, and may mitigate COVID-19 severity through decreased TGF-{beta}1 activation. This therapeutic strategy may be further explored through clinical testing in vulnerable and unvaccinated populations.

LRRC15 is an inhibitory receptor blocking SARS-CoV-2 spike-mediated entry in trans

SARS-CoV-2 infection is mediated by the entry receptor ACE2. Although attachment factors and co-receptors facilitating entry are extensively studied, cellular entry factors inhibiting viral entry are largely unknown. Using a surfaceome CRISPR activation screen, we identified human LRRC15 as an inhibitory receptor for SARS-CoV-2 entry. LRRC15 directly binds to the receptor-binding domain (RBD) of spike protein with a moderate affinity and inhibits spike-mediated entry. Analysis of human lung single cell RNA sequencing dataset reveals that expression of LRRC15 is primarily detected in fibroblasts and particularly enriched in pathological fibroblasts in COVID-19 patients. ACE2 and LRRC15 are not co-expressed in the same cell types in the lung. Strikingly, expression of LRRC15 in ACE2-negative cells blocks spike-mediated viral entry in ACE2+ cell in trans, suggesting a protective role of LRRC15 in a physiological context. Therefore, LRRC15 represents an inhibitory receptor for SARS-CoV-2 regulating viral entry in trans.

Factors Associated with Medication Beliefs in Patients with Parkinson’s Disease: A Cross-Sectional Study

Objective@#Medication beliefs are a significant determinant of medication adherence in chronic illness. This study aimed to identify demographic, clinical, and medication-related factors associated with medication beliefs in patients with Parkinson’s disease (PD). @*Methods@#We used a descriptive cross-sectional design with a convenience sample of 173 PD patients who had been taking antiparkinson drugs for more than one year. @*Results@#The subjects who believed PD medication was more necessary had more severe illness, younger age of onset, longer illness duration, and longer duration of levodopa therapy. They had higher levels of non-motor symptoms and depression, number of medication uses, number of drugs, and levodopa equivalent dose, and they reported fluctuation of motor symptoms and dyskinesia. The subjects who used catechol-O-methyltransferase (COMT) inhibitors, dopamine agonists, amantadine, and monoamine oxidase-B (MAO-B) inhibitors had significantly higher necessity scores than those who did not use them. The subjects who had higher concerns about PD medications had higher levels of non-motor symptoms and depression. The subjects using amantadine and anticholinergics had significantly higher concern scores than those who did not use them. Positive necessity-concerns differentials were associated with severe illness, the presence of motor fluctuation and dyskinesia, and the use of COMT inhibitors. Based on stepwise multiple regression, the most significant factors influencing necessity beliefs were severe illness, followed by depression and motor fluctuation. @*Conclusion@#Severe illness, higher levels of depression, and motor fluctuation are independent factors influencing patients’ beliefs regarding medication necessity. Therefore, these characteristics should be considered in medication belief assessment and interventions for PD patients.

Factors Associated with Medication Beliefs in Patients with Parkinson’s Disease: A Cross-Sectional Study

Objective@#Medication beliefs are a significant determinant of medication adherence in chronic illness. This study aimed to identify demographic, clinical, and medication-related factors associated with medication beliefs in patients with Parkinson’s disease (PD). @*Methods@#We used a descriptive cross-sectional design with a convenience sample of 173 PD patients who had been taking antiparkinson drugs for more than one year. @*Results@#The subjects who believed PD medication was more necessary had more severe illness, younger age of onset, longer illness duration, and longer duration of levodopa therapy. They had higher levels of non-motor symptoms and depression, number of medication uses, number of drugs, and levodopa equivalent dose, and they reported fluctuation of motor symptoms and dyskinesia. The subjects who used catechol-O-methyltransferase (COMT) inhibitors, dopamine agonists, amantadine, and monoamine oxidase-B (MAO-B) inhibitors had significantly higher necessity scores than those who did not use them. The subjects who had higher concerns about PD medications had higher levels of non-motor symptoms and depression. The subjects using amantadine and anticholinergics had significantly higher concern scores than those who did not use them. Positive necessity-concerns differentials were associated with severe illness, the presence of motor fluctuation and dyskinesia, and the use of COMT inhibitors. Based on stepwise multiple regression, the most significant factors influencing necessity beliefs were severe illness, followed by depression and motor fluctuation. @*Conclusion@#Severe illness, higher levels of depression, and motor fluctuation are independent factors influencing patients’ beliefs regarding medication necessity. Therefore, these characteristics should be considered in medication belief assessment and interventions for PD patients.

Lentinula edodes extract inhibits matrix metalloproteinase expression and increases typeⅠprocollagen expression via the p38 MAPK/c-Fos signaling pathway in ultraviolet A and B-irradiated HaCaT keratinocytes

Objective:To determine the effect of Lentinula edodes extract on ultraviolet (UV) A and UVB-induced changes in matrix metalloproteinase (MMP) and typeⅠprocollagen expression using human immortalized HaCaT keratinocytes. Methods:Lentinula edodes ethanol extract (LEE) was obtained by extraction with 80％ ethanol for 4 h at 80 ℃. Effect of LEE on UV-induced alteration on the expression and production of MMPs and typeⅠprocollagen in keratinocytes was investigated using ELISA, RT-PCR, and Western blotting assay. To determine the underlying mechanism of LEE-mediated effects, mitogen-activated protein kinase (MAPK) and activator protein 1 signaling pathways were analysed by Western blotting assay. Results:LEE significantly inhibited the expression of MMP-1 and MMP-9 and increased the expression of typeⅠprocollagen in UVA and UVB-irradiated HaCaT keratinocytes. The phosphorylation levels of p38 were significantly inhibited by LEE whereas it did not affect c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation. Suppression of p38 phosphorylation was also accompanied by downregulation of UVA and UVB-induced increase in c-Fos. Conclusions:LEE effectively inhibits the expression of MMP-1 and MMP-9 and increases typeⅠprocollagen production through the p38 MAPK/c-Fos signaling pathway in UVA and UVB-irradiated HaCaT keratinocytes. This findings suggest that Lentinula edodes may be developed as a cosmetic material to suppress UV exposure-mediated skin aging.

Natural Killer cell activation, reduced ACE2, TMPRSS2, cytokines G-CSF, M-CSF and SARS-CoV-2-S pseudovirus infectivity by MEK inhibitor treatment of human cells

COVID-19 affects vulnerable populations including elderly individuals and patients with cancer. Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells. ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity. We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells. In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi. In serum-deprived and stimulated cells treated with remdesivir and MEKi we observed correlations between pRB, pERK, and ACE2 expression further supporting role of proliferative state and MAPK pathway in ACE2 regulation. We show elevated cytokines in COVID-19-(+) patient plasma (N=9) versus control (N=11). TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir. We observed MEKi stimulation of NK-cell killing of target-cells, without suppressing TRAIL-mediated cytotoxicity. Pseudotyped SARS-CoV-2 virus with a lentiviral core and SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope infected human bronchial epithelial cells, small airway epithelial cells, or lung cancer cells and MEKi suppressed infectivity of the pseudovirus. We show a drug class-effect with MEKi to stimulate NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells. MEKi may attenuate SARS-CoV-2 infection to allow immune responses and antiviral agents to control disease progression.

Hypoxia-induced RelA/p65 derepresses SLC16A3 (MCT4) by downregulating ZBTB7A.

Overexpressed Solute Carrier Family 16 Member 3 (SLC16A3, also called MCT4) plays a critical role in hypoxic cancer cell growth and proliferation, by expelling glycolysis-derived lactate across the plasma membrane. However, how SLC16A3 expression is regulated, under hypoxic conditions, is poorly understood. FBI-1, encoded by ZBTB7A, is a proto-oncoprotein. Interestingly, under hypoxic conditions, expression of SLC16A3, and hypoxia-inducible factor-1 (HIF-1), increased gradually, while FBI-1 expression decreased, suggesting a negative correlation between SLC16A3/HIF-1 and FBI-1 expression. Consequently, we hypothesized that FBI-1 might regulate SLC16A3 and/or HIF-1 expression. Transient transfection and transcription assays of SLC16A3 promoter reporter fusion constructs, oligonucleotide-pulldowns, and ChIP assays, showed that HIF-1α activates SLC16A3 by binding to a hypoxia-response element (HRE), while ectopic FBI-1 potently repressed SLC16A3, by binding to both FBI-1-response elements (FREs) and HREs, during hypoxia. Further evidence for this model was downregulation of ZBTB7A, correlated with SLC16A3 upregulation, in hypoxic colon cancer cells. We also investigated how FBI-1 expression is downregulated during hypoxia. The 5'-upstream regulatory region of ZBTB7A contains two NF-κB-binding sites and two HREs. Interestingly, hypoxia activated NF-κB (RelA/p65) and also increased its nuclear translocation. NF-κB repressed ZBTB7A by binding NF-κB-binding elements, and downregulated the repressor FBI-1, thereby increasing SLC16A3 transcription. While transcriptional repression of SLC16A3 by FBI-1 inhibited lactate efflux, repression of ZBTB7A and activation of lactate efflux by NF-κB, increased colon cancer cell growth and proliferation.

Epigenetic Regulation of Dlg1, via Kaiso, Alters Mitotic Spindle Polarity and Promotes Intestinal Tumorigenesis.

Both alterations to the epigenome and loss of polarity have been linked to cancer initiation, progression, and metastasis. It has previously been demonstrated that loss of the epigenetic reader protein Kaiso suppresses intestinal tumorigenesis in the Apc+/min mouse model, in which altered polarity plays a key role. Thus, we investigated the link between Kaiso deficiency, polarity, and suppression of intestinal tumorigenesis. We used Kaiso-deficient mice to conditionally delete Apc within the intestinal epithelia and demonstrated upregulation of the spindle polarity genes Dlg1 and Dlgap1. To understand the role of Dlg1, we generated Villin-creApc+/minDlg1flx/flx Kaiso-/y mice to analyze gene expression, survival, tumor burden, and spindle orientation. In vivo analysis of the Dlg1-deficient intestine revealed improper orientation of mitotic spindles and a decreased rate of cellular migration. Loss of Dlg1 decreased survival in Apc+/min mice, validating its role as a tumor suppressor in the intestine. Significantly, the increased survival of Apc+/minKaisoy/- mice was shown to be dependent on Dlg1 expression. Taken together, these data indicate that maintenance of spindle polarity in the intestinal crypt requires appropriate regulation of Dlg1 expression. As Dlg1 loss leads to incorrect spindle orientation and a delay in cells transiting the intestinal crypt. We propose that the delayed exit from the crypt increase the window in which spontaneous mutations can become fixed, producing a "tumor-permissive" environment, without an increase in mutation rate. IMPLICATIONS: Loss of mitotic spindle polarity delays the exit of cells from the intestinal crypt and promotes a tumorigenic environment.

Radioembolization for the Treatment of Primary and Metastatic Liver Cancers / 대한핵의학회잡지

Radioembolization using ⁹⁰Y microspheres (glass or resin) has been introduced as an effective intraarterial therapy for unresectable primary and metastatic liver cancers. Although the basic therapeutic effect of chemoembolization results from ischemia, the therapeutic efficacy of radioembolization comes from radiation. Furthermore, compared with surgical resection and local ablation therapy, radioembolization is available with less limitation on the sites or number of liver cancers. The radioisotope ⁹⁰Y is a β-radiation emitter without γ-radiation, with the emission of secondary bremsstrahlung photons and small numbers of positrons. Administration of ⁹⁰Y microspheres into the hepatic artery can deliver a high dose of radiation selectively to the target tumor with limited radiation exposure to the surrounding normal parenchyma, and has low systemic toxicity. In general, radioembolization has been considered for patients with unresectable primary or metastatic liver-only or liver-dominant cancers with no ascites or other clinical signs of liver failure, life expectancy of > 12 weeks, and good performance status. Here, we review the current radioactive compounds, pretreatment assessment, and indications for radioembolization in patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases from colorectal cancer.

Radioembolization for the Treatment of Primary and Metastatic Liver Cancers / 대한핵의학회잡지

Radioembolization using ⁹⁰Y microspheres (glass or resin) has been introduced as an effective intraarterial therapy for unresectable primary and metastatic liver cancers. Although the basic therapeutic effect of chemoembolization results from ischemia, the therapeutic efficacy of radioembolization comes from radiation. Furthermore, compared with surgical resection and local ablation therapy, radioembolization is available with less limitation on the sites or number of liver cancers. The radioisotope ⁹⁰Y is a β-radiation emitter without γ-radiation, with the emission of secondary bremsstrahlung photons and small numbers of positrons. Administration of ⁹⁰Y microspheres into the hepatic artery can deliver a high dose of radiation selectively to the target tumor with limited radiation exposure to the surrounding normal parenchyma, and has low systemic toxicity. In general, radioembolization has been considered for patients with unresectable primary or metastatic liver-only or liver-dominant cancers with no ascites or other clinical signs of liver failure, life expectancy of > 12 weeks, and good performance status. Here, we review the current radioactive compounds, pretreatment assessment, and indications for radioembolization in patients with hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and liver metastases from colorectal cancer.

Factors associated with postpartum health problems among married women of reproductive age in the Democratic Republic of the Congo: a cross-sectional study in Kenge City

Maternal mortality is attracting attention worldwide, but maternal health problems after delivery have received less attention. Most studies focus on prenatal maternal health problems. We aimed to identify factors associated with postpartum health problems among married women of reproductive age in Democratic Republic of the Congo. We employed a cross-sectional study design and randomly enrolled 700 married women of reproductive age in Kenge city. Data collection instrument was developed using the UNICEF Multiple Indicator Cluster Survey. T-test, chi-square test, and binary logistic regression analysis were performed using the SPSS version 24.0. Significant risk factors associated with postpartum health problems were initial postnatal care period; within 24 hours (Odds Ratio [OR]=2.197, 95% confidence interval [CI]: [1.156­4.174], p=.016); within 7 days (OR=1.972, 95% CI: [1.102­3.528, p=.022]; within 14 days (OR=2.124, 95% CI: [1.082­4.172], p=.029) among reproductive health and health service utilization characteristics. Health education by RECO (Relais Cmunataure) was associated with postpartum health problems including PCIME (Prise en Charge Integree des Maladies de l'Enfant; OR=1.845, 95% CI: [1.038­3.282], p=.037); hand washing (OR=1.897, 95% CI: [1.060­3.396], p=.031); malaria (OR=2.003, 95% CI: [1.192­3.366], p=.009) among Maternal and Child Health intervention characteristics. In conclusion, it is necessary to develop and promote health policies and educational programs focusing on PNC service within 24 hours, PNC services within 7 days, PCIME, hand washing, prevention of malaria

Apoptotic cells trigger the ABCA1/STAT6 pathway leading to PPAR-γ expression and activation in macrophages.

The signal transducer and activator of transcription 6 (STAT6) transcription factor activates peroxisome proliferator-activated receptor gamma (PPAR-γ)-regulated gene expression in immune cells. We investigated proximal membrane signaling that was initiated in macrophages after exposure to apoptotic cells that led to enhanced PPAR-γ expression and activity, using specific siRNAs for ABCA1, STAT6, and PPAR-γ, or their antagonists. The interactions between mouse bone marrow-derived macrophages or RAW 264.7 cells and apoptotic Jurkat cells, but not viable cells, resulted in the induction of STAT6 phosphorylation as well as PPAR-γ expression and activation. Knockdown of ATP-binding cassette transporter A1 (ABCA1) after the transfection of macrophages with ABCA1-specific siRNAs reduced apoptotic cell-induced STAT6 phosphorylation as well as PPAR-γ mRNA and protein expression. ABCA1 knockdown also reduced apoptotic cell-induced liver X receptor α (LXR-α) mRNA and protein expression. Moreover, inhibition of STAT6 with specific siRNAs or the pharmacological inhibitor AS1517499AS reversed the induction of PPAR-γ, LXR-α, and ABCA1 by apoptotic Jurkat cells. PPAR-γ-specific siRNAs or the PPAR-γ antagonist GW9662 inhibited apoptotic cell-induced increases in LXR-α and ABCA1 mRNA and protein levels. Thus, these results indicate that apoptotic cells trigger the ABCA1/STAT6 pathway, leading to the activation of the PPAR-γ/LXR-α/ABCA1 pathway in macrophages.

A STAT6 Inhibitor AS1517499 Reduces Preventive Effects of Apoptotic Cell Instillation on Bleomycin-Induced Lung Fibrosis by Suppressing PPARγ.

BACKGROUND/AIMS: The signal transducer and activator of transcription 6 (STAT6) transcription factor mediates PPARγ-regulated gene expression in macrophages. However, it remains largely unknown how proximal membrane signaling events initiated by apoptotic cell recognition upregulate PPARγ expression and activate the lung homeostatic program. METHODS: The STAT6 inhibitor AS1517499 was used to determine the role of STAT6 in mediating PPARγ activity, anti-inflammatory effects, and anti-fibrotic effects induced by apoptotic cell instillation after bleomycin treatment into C57BL/6 mice. Bronchoalveolar lavage fluid, alveolar macrophages and lungs were harvested at days 2, 7, and 14 and then analyzed by real-time PCR, immunoblotting, ELISA, immunocytochemistry and immunohistochemistry assays. RESULTS: Our data demonstrate that apoptotic cell instillation after bleomycin results in prolonged enhancement of STAT6 phosphorylation in alveolar macrophages and lung. Co-administration of the STAT6 inhibitor, AS1517499, reversed the enhanced PPARγ expression and activity induced by apoptotic cell instillation after bleomycin treatment. By reducing the expression of PPARγ target genes, including CD36, macrophage mannose receptor, and arginase 1, AS1517499 inhibited efferocytosis and restored pro-inflammatory cytokine expression, neutrophil recruitment, protein levels, hydroxyproline content, and expression of fibrosis markers, including type 1 collagen α2, fibronectin, and α-smooth muscle actin. STAT6 inhibition reversed the expression profile of hepatocyte growth factor and interleukin-10. CONCLUSION: These results indicate that prolonged STAT6 activation following one-time apoptotic cell instillation facilitates continuous PPARγ activation, resulting in the resolution of bleomycin-induced lung inflammation and fibrosis.

Evaluation of Hot Nodules of Thyroid Gland Using Tc-99m Pertechnetate: a Novel Approach Using Quantitative Single-Photon Emission Computed Tomography/Computed Tomography / 대한핵의학회잡지

Planar scintigraphy using Tc-99mpertechnetate is useful for snapshot evaluation of hot thyroid nodules, which are pathologically follicular adenoma and seldom, if ever, malignant. The autonomy of the hot nodules has been demonstrated by the presence of thyroid-stimulating hormone-dependent extra-nodular thyroid tissue besides the hot nodules. Here, we present two cases of hot thyroid nodules in patients who underwent quantitative single-photon emission computed tomography/computed tomography (SPECT/CT). In addition to the nodules, contralateral normal thyroid parenchyma was evaluated based on standardized uptake values. One patient had a traditional follicular adenoma suppressing other thyroid tissue, whereas the other patient seemed to have a nodule erupting from underlying hyperfunctioning, not suppressed, thyroid tissue. This novel approach using quantitative SPECT/CT unveils a new pathology of hot thyroid nodule that does not suppress, but coincides with hyperfunctioning thyroid tissue.

Evaluation of Hot Nodules of Thyroid Gland Using Tc-99m Pertechnetate: a Novel Approach Using Quantitative Single-Photon Emission Computed Tomography/Computed Tomography / 대한핵의학회잡지

Planar scintigraphy using Tc-99mpertechnetate is useful for snapshot evaluation of hot thyroid nodules, which are pathologically follicular adenoma and seldom, if ever, malignant. The autonomy of the hot nodules has been demonstrated by the presence of thyroid-stimulating hormone-dependent extra-nodular thyroid tissue besides the hot nodules. Here, we present two cases of hot thyroid nodules in patients who underwent quantitative single-photon emission computed tomography/computed tomography (SPECT/CT). In addition to the nodules, contralateral normal thyroid parenchyma was evaluated based on standardized uptake values. One patient had a traditional follicular adenoma suppressing other thyroid tissue, whereas the other patient seemed to have a nodule erupting from underlying hyperfunctioning, not suppressed, thyroid tissue. This novel approach using quantitative SPECT/CT unveils a new pathology of hot thyroid nodule that does not suppress, but coincides with hyperfunctioning thyroid tissue.

Nefopam does not influence onset and recovery profiles of rocuronium-induced neuromuscular block: a prospective, double-blinded, randomized, controlled study

BACKGROUND: We investigated the hypothesis that pretreatment with nefopam 20 mg would influence the onset and recovery profiles of rocuronium-induced neuromuscular block. METHODS: After Institutional Review Board approval, 134 patients, aged between 20–65 years, belonging to the American Society of Anesthesiologists physical status classification I or II, were randomly allocated to receive either 0.9% normal saline (control group) or nefopam 20 mg (nefopam group), infused over one hour before induction of anesthesia. Anesthesia was induced with remifentanil and propofol, followed by endotracheal intubation with rocuronium 0.6 mg/kg. We recorded the lag time, onset time, clinical duration, recovery index, recovery time, and total recovery time. RESULTS: We included 111 patients in the final analysis. The lag time, onset time, clinical duration, recovery index, recovery time, and total recovery time of the nefopam group (n = 57) were not significantly different compared with that of the control group (n = 54). CONCLUSIONS: Pretreatment with nefopam 20 mg one hour before induction of anesthesia does not have a significant influence on the onset and recovery profiles of rocuronium-induced neuromuscular block.

Utility of Quantitative Parameters from Single-Photon Emission Computed Tomography/Computed Tomography in Patients with Destructive Thyroiditis

OBJECTIVE: Quantitative parameters from Tc-99m pertechnetate single-photon emission computed tomography/computed tomography (SPECT/CT) are emerging as novel diagnostic markers for functional thyroid diseases. We intended to assess the utility of SPECT/CT parameters in patients with destructive thyroiditis. MATERIALS AND METHODS: Thirty-five destructive thyroiditis patients (7 males and 28 females; mean age, 47.3 ± 13.0 years) and 20 euthyroid patients (6 males and 14 females; mean age, 45.0 ± 14.8 years) who underwent Tc-99m pertechnetate quantitative SPECT/CT were retrospectively enrolled. Quantitative parameters from the SPECT/CT (%uptake, standardized uptake value [SUV], thyroid volume, and functional thyroid mass [SUVmean × thyroid volume]) and thyroid hormone levels were investigated to assess correlations and predict the prognosis for destructive thyroiditis. The occurrence of hypothyroidism was the outcome for prognosis. RESULTS: All the SPECT/CT quantitative parameters were significantly lower in the 35 destructive thyroiditis patients compared to the 20 euthyroid patients using the same SPECT/CT scanner and protocol (p < 0.001 for all parameters). T3 and free T4 did not correlate with any SPECT/CT parameters, but thyroid-stimulating hormone (TSH) significantly correlated with %uptake (p = 0.004), SUVmean (p < 0.001), SUVmax (p = 0.002), and functional thyroid mass (p < 0.001). Of the 35 destructive thyroiditis patients, 16 progressed to hypothyroidism. On univariate and multivariate analyses, only T3 levels were associated with the later occurrence of hypothyroidism (p = 0.002, exp(β) = 1.022, 95% confidence interval: 1.008 – 1.035). CONCLUSION: Novel quantitative SPECT/CT parameters could discriminate patients with destructive thyroiditis from euthyroid patients, suggesting the robustness of the quantitative SPECT/CT approach. However, disease progression of destructive thyroiditis could not be predicted using the parameters, as these only correlated with TSH, but not with T3, the sole predictor of the later occurrence of hypothyroidism.

Awareness about past diagnosis and treatment history: nationwide survey of childhood cancer survivors and their parents.

OBJECTIVE: To assess the awareness of past medical history and long-term care issues of childhood cancer survivors (CCS) in Korea. METHODS: A nationwide survey was conducted on CCS and their parents in 10 regional cancer centers in Korea. Answers regarding cancer diagnosis and treatment history were compared with the treatment summary and categorized into three ('specific,' 'general,' and 'no') or two ('yes' and 'no') groups. RESULTS: Out of 343 contacts, 293 dyads completed the survey, and 281 dyads were analyzed. Awareness of cancer diagnosis was mostly specific for parents (76.5%) and CCS (35.2%). Awareness of anti-cancer treatment exposure was mostly general (84.6% for surgery, 67.9% for chemotherapy, and 53.9% for hematopoietic stem cell transplantation) rather than specific. In particular, more than half of the parents were not aware of the exposure to cardiotoxic agents (72.9%) or radiation therapy (56.3%). Providing information about long-term side effects and prevention of secondary cancer was significantly correlated only with more concern and more follow-up visits (P ≤ 0.001, respectively), without correlation with more specific awareness of exposure to cardiotoxic agents or radiation. CONCLUSION(S): Most of the parents of CCS were not aware of treatment-related risk factors necessary for long-term care. Providing information was significantly correlated with more concern and more follow-up visits, without improving corresponding knowledge about their past medical history. Effort aimed towards improving awareness about risk factors, the manner of providing information, and the patient referral system within which we use this information is warranted.