Trabecular Bone Score and Central Quantitative Computed Tomography for the Prediction of Vertebral Fragility Fractures in Postmenopausal Women

Background@#We aimed to investigate whether densitometry results and volumetric bone mineral density (vBMD) can predict vertebral fragility fractures (VFF) in postmenopausal women. @*Methods@#We enrolled 271 postmenopausal women aged >45 years who visited our hospital for health check-ups between September 2016 and September 2017. The lumbar spine (LS) and femoral neck (FN) densitometry results and trabecular bone score (TBS) were calculated using dual energy X-ray absorptiometry. vBMD was assessed using central quantitative computed tomography (cQCT). Baseline and follow-up X-ray images were reviewed to evaluate thoracolumbar vertebral compression fractures (CFs), according to the Genant criteria. @*Results@#At baseline, 76 patients (28.0%) had CF. Additional or progressive fractures were noted in 26 participants (9.6%) with a median follow-up of 19.5 months. The median TBS and cQCT were significantly higher in participants without baseline CF than those with baseline CF (p<0.001). During the follow-up, Kaplan–Meier analysis showed that T-scores of the LS and FN <-2.5, degraded microarchitecture based on the TBS (≤1.200), and vBMD <80 mg/cm3 was significantly associated with future osteoporotic CF. The final multivariate Cox regression analysis showed that baseline CF and low TBS and vBMD were significant risk factors for future VFF. @*Conclusions@#Participants with baseline CF and degraded microarchitecture had higher CF predisposition. Moreover, cQCT can predict future vertebral fractures.

Effectiveness of prophylactic calcium and vitamin D supplementation for preventing post-thyroidectomy hypocalcemia: a meta-analysis / 고신대학교의과대학학술지

Background@#Postsurgical hypocalcemia is the most common and troublesome consequence of thyroidectomy. We investigated the potential role of routine calcium or vitamin D supplementation in preventing postsurgical hypocalcemia. @*Methods@#We searched MEDLINE and Embase for English-language publications using the keywords “calcium,” “vitamin D,” and “thyroid cancer.” The primary outcome was any postoperative hypocalcemia, and the secondary outcome was symptomatic hypocalcemia. @*Results@#Four studies that included 381 patients were eligible for this meta-analysis. A random-effects model showed no significant difference in the occurrence of hypocalcemia between calcium/vitamin D treatment and placeboo treatment. However, the occurrence of symptomatic hypocalcemia was lower in patients with calcium/vitamin D treatment. In the combined results, preoperative calcium and vitamin D supplementation were associated with a reduced incidence of symptomatic hypocalcemia. @*Conclusions@#Our findings support the use of preoperative calcium and vitamin D supplementation in conjunction with routine postsurgical supplementation for patients after total thyroidectomy.

A New Murine Liver Fibrosis Model Induced by Polyhexamethylene Guanidine-Phosphate

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

Sleep and Neuroimaging / 대한핵의학회잡지

We spend about one-third of our lives either sleeping or attempting to sleep. Therefore, the socioeconomic implications of sleepdisorders may be higher than expected. However, the fundamental mechanisms and functions of sleep are not yet fully understood.Neuroimaging has been utilized to reveal the connectivity between sleep and the brain, which is associated with thephysiology of sleep. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) imagingstudies have become increasingly common in sleep research. Recently, significant progress has been made in understanding thephysiology of sleep through neuroimaging and the use of various radiopharmaceuticals, as the sleep–wake cycle is regulated bymultiple neurotransmitters, including dopamine, adenosine, glutamate, and others. In addition, the characteristics of rapid eye andnon-rapid eye movement sleep have been investigated by measuring cerebral glucose metabolism. The physiology of sleep hasbeen investigated using PET to study glymphatic function as a means to clear the amyloid burden. However, the basic mechanismsand functions of sleep are not yet fully understood. Further studies are needed to investigate the effects and consequencesof chronic sleep deprivation, and the relevance of sleep to other diseases.

Effect of Single-Nucleotide Polymorphisms on Decline of Dopamine Transporter Availability in Parkinson's Disease

BACKGROUND AND PURPOSE: We aimed to determine the association between the annual changes in dopamine transporter (DAT) availability as measured by 123I-ioflupane (123I-FP-CIT) single-photon-emission computed tomography and single-nucleotide polymorphisms (SNPs) known to be risk factors in Parkinson's disease (PD). METHODS: In total, 150 PD patients were included from the Parkinson's Progression Markers Initiative database. Specific SNPs that are associated with PD were selected for genotyping. SNPs that were not in Hardy-Weinberg equilibrium or whose minor allele frequency was less than 0.05 were excluded. Twenty-three SNPs met the inclusion criteria for this study. The Kruskal-Wallis test was used to compare annual percentage changes in DAT availability for three subgroups of SNP. RESULTS: None of the 23 SNPs exerted a statistically significant effect (p < 0.0022) on the decline of DAT availability in PD patients. However, we observed trends of association (p < 0.05) between three SNPs of two genes with the annual percentage change in DAT availability: 1) rs199347 on the putamen (p=0.0138), 2) rs356181 on the caudate nucleus (p=0.0105), and 3) rs3910105 on the caudate nucleus (p=0.0374). A post-hoc analysis revealed that DAT availability was reduced the most for 1) the putamen in the CC genotype of rs199347 (vs. CT, p=0.0199; vs. TT, p=0.0164), 2) the caudate nucleus in the TT genotype of rs356181 (vs. CC, p=0.0081), and 3) the caudate nucleus in the CC genotype of rs3910105 (vs. TT, p=0.0317). CONCLUSIONS: Significant trends in the associations between three SNPs and decline of DAT availability in PD patients have been discovered.

Effects of Thyrotropin Suppression on Bone Health in Menopausal Women with Total Thyroidectomy

BACKGROUND: This study examined the change in the trabecular bone score (TBS), areal bone mineral density (aBMD), and osteoporosis in postmenopausal women who underwent thyrotropin (TSH)-suppressive therapy for treating papillary thyroid cancer after a total thyroidectomy procedure. METHODS: We evaluated 36 postmenopausal women who received a total thyroidectomy for papillary thyroid cancer and were undergoing TSH suppressive therapy with levothyroxine. Postmenopausal women (n=94) matched for age and body mass index were recruited as healthy controls. The aBMD and TBS of the lumbar spine were compared between dual energy X-ray absorptiometry (DXA) at baseline and at follow-up after an average of 4.92 years. RESULTS: There was no significant difference in the rate of diagnoses of osteoporosis, osteopenia, or normal bone status between the 2 groups during the baseline DXA evaluation. However, the TBS was significantly lower whereas aBMD did not show significant difference at the time of baseline DXA measurement (1st DXA, 1.343±0.098 vs. 1.372±0.06317, P < 0.001; 2nd DXA, 1.342±0.095 vs. 1.370±0.062, P < 0.001). The TBS and aBMD did not differ significantly between the initial and follow-up DXA images in both groups of TSH suppressive patients and controls. CONCLUSIONS: The average value of TBS and aBMD did not significantly change during the follow-up period. The TSH suppressive therapy was revealed as not a significant factor for the progressive deterioration of bone status during long term follow-up.

Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors / 대한핵의학회잡지

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.

Lu-177-Based Peptide Receptor Radionuclide Therapy for Advanced Neuroendocrine Tumors / 대한핵의학회잡지

Peptide receptor radionuclide therapy (PRRT) is a systemic cytotoxic radiation therapy using a compound of β-emitting radionuclide chelated to a peptide for the treatment of tumor with overexpressed specific cell receptor such as somatostatin receptor subtype 2 (SSTR2) of neuroendocrine tumor (NET). Surgical resection should be performed for the curative treatment for NETs when it is feasible; however, a multi-disciplinary approach is needed when locally advanced or metastasized disease. PRRT with lutetium-177 (Lu-177)-labeled somatostatin analogues, as a new treatment modality targeting metastatic or inoperable NETs expressing the SSTR2, have been developed and successfully used for the past two decades. As Lu-177 emits both β- and γ-radiation, it has the ability as a theragnostic agent for NETs compared with only β-emitting yttrium-90 labeled PRRT. Several recent studies reported that Lu-177 gave an overall positive response and improved the patients' quality of life. To fully exploit its potential, large comparative studies are needed for the assessment of distinct efficacies of Lu-177 labeled PRRT. Additionally, for extending the indications and developing new regimens of Lu-177-based PRRT, more dedicated clinical research is required.

IL-2-enhanced NK Cell Cytotoxicity is Regulated by Adiponectin from Hypothalamo-pituitary-adrenal Axis

BACKGROUND: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. METHODS: Signal sequence trap was used to find stress novel secretory protein from HPA-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. RESULTS: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. CONCLUSION: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

IL-2-enhanced NK Cell Cytotoxicity is Regulated by Adiponectin from Hypothalamo-pituitary-adrenal Axis

BACKGROUND: The Hypothalamo-Pituitary-Adrenal (HPA) axis is an important regulator for the body's stress response. As a primary stress responsive system, HPA-axis secretes various neurotransmitters, hormones, and cytokines, which regulates the immune system. Natural killer (NK) cell which is plays an important role in the innate immune response, is specially decreased their numbers and loose cytolytic activity in response to stress. However, the effect of HPA-axis secreted proteins on NK cell activity has not been defined. Herein, we studied the effect of adrenal secreted adiponectin on NK cell cytotoxicity. Adiponectin which is well-known metabolic control protein, plays important roles in various diseases, including hypertension, cardiovascular diseases, inflammatory disorders, and cancer. METHODS: Signal sequence trap was used to find stress novel secretory protein from HPA-axis. Selected adiponectin was treated mouse mature primary NK cells and then examined the effect of adiponectin to NK cell cytotoxicity and cytokine expression level. RESULTS: We found that adiponectin which is secreted from adrenal gland, suppress IL-2 induced NK cell cytotoxicity. And also investigated cytolytic cytokines are suppressed by adiponectin. CONCLUSION: These data suggest that adiponectin inhibites NK cell cytotoxicity via suppression of cytotoxicity related target gene.

3-Dimensional Analyses of Eye Motion in Oculopalatal Tremor

BACKGROUND: Oculopalatal tremor (OPT) is a delayed complication of damage to the dentato-rubro-olivary pathway (Guillain-Mollaret triangle) and subsequent hypertrophic olivary degeneration. Mixed torsional-vertical pendular nystagmus in OPT has been considered to signify unilateral brainstem damage while symmetrical vertical nystagmus has been regarded to indicate bilateral disease. However, 3-dimensional oculographic analysis of OPT has been sparse. METHODS: In 8 patients with OPT; binocular 3-dimensional analyses of ocular oscillations were performed by using a magnetic search coil technique. Lateralization of the lesions was determined by the imaged olivary hypertrophy in the MRI. RESULTS: One patient had conjugate vertical pendular nystagmus and four showed mixed torsional-vertical pendular nystagmus. Two patients showed mixed horizontal-torsional-vertical nystagmus. One patient had predominantly horizontal pendular nystagmus. MRI demonstrated increased signal or hypertrophy of the inferior olivary nucleus, unilateral in six and bilateral in two. Unilateral olivary changes were associated with mixed torsional-vertical nystagmus in three patients, mixed horizontal-torsional-vertical nystagmus in another two patients, and predominantly horizontal pendular nystagmus in the remaining one patient. Bilateral olivary changes were visible in one patient with conjugate vertical pendular nystagmus and in the other patient with mixed torsional-vertical nystagmus. Palatal tremor appeared to be symmetrical in all patients. CONCLUSIONS: Three-dimensional analyses of OPT indicate that conjugate vertical and mixed torsional-vertical pendular nystagmus do not correspond to the laterality of signal changes in the inferior olivary nucleus. Ocular oscillations often have all the vertical, horizontal and torsional components.