Mitochondria-derived peptide SHLP2 regulates energy homeostasis through the activation of hypothalamic neurons.

Small humanin-like peptide 2 (SHLP2) is a mitochondrial-derived peptide implicated in several biological processes such as aging and oxidative stress. However, its functional role in the regulation of energy homeostasis remains unclear, and its corresponding receptor is not identified. Hereby, we demonstrate that both systemic and intracerebroventricular (ICV) administrations of SHLP2 protected the male mice from high-fat diet (HFD)-induced obesity and improved insulin sensitivity. In addition, the activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus (ARC) is involved in the suppression of food intake and the promotion of thermogenesis. Through high-throughput structural complementation screening, we discovered that SHLP2 binds to and activates chemokine receptor 7 (CXCR7). Taken together, our study not only reveals the therapeutic potential of SHLP2 in metabolic disorders but also provides important mechanistic insights into how it exerts its effects on energy homeostasis.

A Case of Adenomyosis Showing Size Reduction in a Follicular Lymphoma Patient Receiving Chemotherapy With R-Bendamustine.

ABSTRACT: We describe a case of adenomyosis that reduced in size in a patient with lymphoma on receiving chemotherapy. A 48-year-old woman with worsening left flank pain was diagnosed with follicular lymphoma. [ 18 F]FDG PET/CT revealed multiple hypermetabolic lymph nodes in the bilateral cervical, axillary, mediastinal, mesenteric, retroperitoneal, iliac, and inguinal regions. In addition, adenomyosis with mild hypermetabolism was demonstrated on [ 18 F]FDG PET/CT. The size and metabolism of adenomyosis decreased after chemotherapy with R-bendamustine; in addition, along with decrease in estradiol levels, the patient experienced amenorrhea and hot flushes. The patient was diagnosed with chemotherapy-induced early menopause.

Obesity mechanism after hypothalamic damage: Cohort analysis of neuroimaging, psychological, cognitive, and clinical phenotyping data.

Objective: The hypothalamus regulates energy homeostasis, and its damage results in severe obesity. We aimed to investigate the multifaceted characteristics of hypothalamic obesity. Methods: We performed multidimensional analyses of brain structure/function and psychological and behavioral phenotypes in 29 patients with hypothalamic damage (HD) (craniopharyngioma) and 31 controls (non-functional pituitary adenoma). Patients underwent structural and functional magnetic resonance imaging and completed self-reports and cognitive tasks. Results: Patients with HD showed significantly higher postoperative weight gain than controls. The HD group also showed significant hypothalamic damage and lower neural activation in the left caudate nucleus in response to food images. The HD group had significantly higher food inattention, lower satiety, and higher restrained eating behavior. Within the HD group, higher restrained eating behavior was significantly associated with lower activation in the bilateral fusiform gyrus. Conclusion: These results suggest that hypothalamic damage contributes to weight gain by altering the brain response, attention, satiety, and eating behaviors. The present study proposes novel neuro-psycho-behavioral mechanisms targeted for patients with hypothalamic obesity.

Objective analysis of facial bone fracture CT images using curvature measurement in a surface mesh model.

The human facial skeleton consists of multiple segments and causes difficulty during analytic processes. We developed image analysis software to quantify the amount of injury and validate the smooth curvature of the surface after facial bone reduction surgery. Three-dimensional computed tomography images of facial bone were obtained from 40 patients who had undergone open reduction surgery to treat unilateral zygomaticomaxillary fractures. Analytic software was developed based on the discrete curvature of a triangular mesh model. The discrete curvature values were compared before and after surgery using two regions of interest. For the inferior orbital rim, the weighted average of curvature changed from 0.543 ± 0.034 to 0.458 ± 0.042. For the anterior maxilla, the weighted average of curvature changed from 0.596 ± 0.02 to 0.481 ± 0.031, showing a significant decrement (P < 0.05). The curvature was further compared with the unaffected side using the Bray-Curtis similarity index (BCSI). The BCSI of the inferior orbital rim changed from 0.802 ± 0.041 to 0.904 ± 0.015, and that for the anterior maxilla changed from 0.797 ± 0.029 to 0.84 ± 0.025, demonstrating increased similarity (P < 0.05). In computational biology, adequate analytic software is crucial. The newly developed software demonstrated significant differentiation between pre- and postoperative curvature values. Modification of formulas and software will lead to further advancements.

Assessment of Instability in Thoracolumbar Burst Fractures Using a New Bone Scan Scoring System.

Background and Objectives: Unstable thoracolumbar burst fractures require surgical management as they can result in neurological deficits if left untreated. This study aimed to evaluate whether a new bone scan scoring system could accurately assess instability in thoracolumbar burst fractures. Materials and Methods: Fifty-two patients with thoracolumbar burst fractures who underwent bone scans and magnetic resonance imaging prior to surgery between January 2015 and August 2017 at Ulsan University Hospital were selected for inclusion. Instability was determined by clinical assessment and imaging, and the Thoracolumbar Injury Classification and Severity score was determined. Bone scans were visually evaluated using a new bone scan scoring system. Bone scan findings of vertebral body (BB) and posterior column (BP) were scored separately and were summed to produce BTS {BTS (total score) = BB (body score, 5 points) + BP (posterior score, 2 points)}. The diagnostic performance of the scoring system for identifying unstable then thoracolumbar burst fractures were assessed. Results: Of the 52 thoracolumbar burst fractures, 34 (65.4%) were unstable and 31 (59.6%) had a Thoracolumbar Injury Classification and Severity score ≥ 5. The diagnostic performance of using BTS ≥ 4 to identify unstable thoracolumbar burst fractures and those with a Thoracolumbar Injury Classification and Severity score ≥ 5 was as follows: sensitivity, 61.8% and 58.1%; specificity, 94.4% and 81.0%; positive predictive value, 95.5% and 81.8%; and negative predictive value, 56.7% and 56.7%, respectively. Conclusions: The proposed bone scan scoring system has a high specificity and positive predictive value for identifying thoracolumbar burst fractures that are unstable or have a Thoracolumbar Injury Classification and Severity score ≥ 5. This scoring system may help to inform decisions regarding surgical management.

Determinants of Short-Term Weight Gain Following Surgical Treatment for Craniopharyngioma in Adults.

OBJECTIVE: Craniopharyngiomas (CPs) are associated with hypothalamic damage that causes hypothalamic obesity, however, the mechanisms underlying CP-related postoperative weight gain remain debatable. This study aimed to elucidate whether the major determinant of postoperative weight gain in patients with CP is hypothalamic injury or steroid replacement therapy. METHODS: We included 48 adult patients with CP (age ≥18 years) who underwent transsphenoidal surgery between 2010 and 2018 in a single tertiary center, and whose body weight was measured pre- and postoperatively (<120 days after the surgery). We recruited 144 age- and body mass index-matched patients with non-functioning pituitary adenoma (NFPA) as controls. RESULTS: Patients with CP experienced greater postoperative weight gain than patients with NFPA (3.0±5.1 vs. 0.1±3.6 kg, p<0.001). The prevalence of postoperative steroid use was significantly higher in patients with CP than in those with NFPA (89.6% vs. 34.0%, p<0.001). Steroid replacement therapy and CP were associated with postoperative weight gain after adjusting for covariates in overall patients (p=0.032 and 0.007, respectively). In subgroup analysis with postoperative steroid users, weight gain was significantly greater in patients with CP (n=43, 0.96±0.25 kg/month) than in patients with NFPA (n=49, 0.26±0.23 kg/month) even after adjusting for the daily steroid dose (p=0.048). CONCLUSION: Patients with CP experience greater postoperative weight gain than those with NFPA. Hypothalamic damage itself as well as steroid replacement may contribute to the postoperative weight gain in patients with CP.

χ-separation: Magnetic susceptibility source separation toward iron and myelin mapping in the brain.

Obtaining a histological fingerprint from the in-vivo brain has been a long-standing target of magnetic resonance imaging (MRI). In particular, non-invasive imaging of iron and myelin, which are involved in normal brain functions and are histopathological hallmarks in neurodegenerative diseases, has practical utilities in neuroscience and medicine. Here, we propose a biophysical model that describes the individual contribution of paramagnetic (e.g., iron) and diamagnetic (e.g., myelin) susceptibility sources to the frequency shift and transverse relaxation of MRI signals. Using this model, we develop a method, χ-separation, that generates the voxel-wise distributions of the two sources. The method is validated using computer simulation and phantom experiments, and applied to ex-vivo and in-vivo brains. The results delineate the well-known histological features of iron and myelin in the specimen, healthy volunteers, and multiple sclerosis patients. This new technology may serve as a practical tool for exploring the microstructural information of the brain.

Integrative analysis of genetic and clinical risk factors for bone loss in a Korean population.

PURPOSE: The relative contribution of genetic and clinical factors for bone loss is not well known. This study aimed to investigate the annualized percentage change in total hip bone mineral density (BMD) and the genetic and clinical risk factors for bone loss in a Korean prospective cohort study over a 6-year period. METHODS: We included 645 men aged ≥50 years and 683 postmenopausal women who had repeated BMD testing between 2007 and 2014. The association between covariates and annualized percentage change in hip BMD was analyzed through the multivariate linear regression analysis. A total of 2614 single-nucleotide polymorphisms (SNPs) from 23 known BMD-related candidate genes and genome-wise association study were investigated. RESULTS: Hip bone loss increased more rapidly in women than in men with advancing age. Hip bone loss in men increased with lean mass (LM) loss (%/year) (P < 0.001) and current smoking (P = 0.024) and decreased with increasing waist circumference (WC) (P < 0.001), alcohol consumption (P = 0.049), and increase in red blood cell counts (P = 0.031). Decreasing WC (P = 0.009), LM loss (%/year) (P < 0.001), and years since menopause ≤ 3 years (P = 0.003) significantly correlated with hip bone loss in women aged 45-59 years. Hip bone loss in women aged ≥60 years increased with advancing age (P = 0.012), alcohol consumption (P = 0.028), LM loss (%/year) (P = 0.031), and fat mass loss (%/year) (P < 0.001) and decreased with increasing WC (P = 0.025). LRP5 rs498830 (ß = 0.127, P = 0.007) and TNFSF11 rs7325635 (ß = 0.146, P = 0.001) were the top SNPs related to hip bone loss in men and postmenopausal women, respectively. However, none of the SNPs were associated with hip bone loss after Benjamini-Hochberg adjustment. CONCLUSION: In this study, decreasing WC and LM were significant risk factors for hip bone loss in both men and women. Those factors were also identified that had sex-specific or age-specific effects on hip bone loss. None of the SNPs were associated with hip bone loss after multiple testing adjustments. The understanding of the modifiable factors contributing to bone loss has been broadened, and this may have implications such as in developing individualized preventive strategy. Further studies are needed to better predict the risk for bone loss in men and women.

Clinical effectiveness of liraglutide on weight loss in South Koreans: First real-world retrospective data on Saxenda in Asia.

ABSTRACT: Among Asian countries, South Korea was the first to approve liraglutide as a treatment for obesity. Thus, the clinical effectiveness of liraglutide has not been studied in Asian populations.In this study, we retrospectively analyzed obese patients [body mass index (BMI) >27 kg/m2] who were treated with liraglutide between March 2018 and March 2019 in a single clinic. Weight, BMI, HbA1c, and clinical data were collected before liraglutide treatment. Changes in body weight and composition and their relationships with clinical variables were examined at re-prescription dates within 30, 60, 90, and 180 days.A total of 169 subjects were studied. The average age was 41.5 years, and 42% of the subjects were male. The average weight was 85.2 kg, and the average BMI was 30.8 kg/m2. Weight reduction was significant (-5.5 ±â€Š3.4 kg, 30 days: -3.2 ±â€Š1.8 kg, 60 days: -4.5 ±â€Š2.3 kg, 90 days: -6.3 ±â€Š2.6 kg, 180 days: -7.8 ±â€Š3.5 kg) during the follow-up period and increased with longer treatment time (P < .001). The percentages of subjects that showed ≥ 5% and ≥ 10% body weight reduction were 62.1% and 17.2%, respectively. In the body composition analysis, skeletal muscle weight loss was -3.56 ±â€Š29.7%, which was significantly smaller than fat weight loss of -11.06 ±â€Š10.4% (P = .03). Weight loss was not significantly related to age, sex, baseline BMI, baseline HbA1c, smoking status, alcohol consumption, coffee intake.In conclusion, Liraglutide treatment led to meaningful weight loss in South Korean patients, and fat mass reduction was prominent during treatment. Furthermore, liraglutide showed greater clinical effectiveness with longer treatment time.

Clinical Implication of Individually Tailored Segmentation Method for Distorted Hypothalamus in Craniopharyngioma.

Objective: Several attempts have been done to capture damaged hypothalamus (HT) using volumetric measurements to predict the development of hypothalamic obesity in patients with craniopharyngioma (CP). This study was to develop a novel method of HT volume measurement and examine the associations between postoperative HT volume and clinical parameters in patients with CP. Methods: We included 78 patients with adult-onset CP who underwent surgical resection. Postoperative HT volume was measured using T1- and T2-weighted magnetic resonance imaging (MRI) with a slice thickness of 3 mm, and corrected for temporal lobe volume. We collected data on pre- and postoperative body weights, which were measured at the time of HT volume measurements. Results: The corrected postoperative HT volume measured using T1- and T2-weighted images was significantly correlated (r=0.51 [95% confidence interval (CI) 0.32 to 0.67], P<0.01). However, HT volume was overestimated using T1-weighted images owing to obscured MR signal of the thalamus in patients with severe HT damage. Therefore, we used T2-weighted images to evaluate its clinical implications in 72 patients with available medical data. Postoperative HT volume was negatively associated with preoperative body weight and preoperative tumor volume (r=-0.25 [95% CI -0.45 to -0.04], P=0.04 and r=-0.26 [95% CI -0.40 to -0.15], P=0.03, respectively). In the subgroup analysis of CP patients who underwent primary surgery (n=56), pre- and postoperative body weights were negatively associated with HT volume (r=-0.30 [95% CI -0.53 to -0.03], P=0.03 and r=-0.29 [95% CI -0.53 to -0.02], P=0.03, respectively). Conclusions: Adult-onset CP patients showed negative associations between postoperative HT volume and preoperative/postoperative body weight using a new method of HT volume measurement based on T2-weighted images.

Early-Phase SPECT/CT for Diagnosing Osteomyelitis: A Retrospective Pilot Study.

OBJECTIVE: The aim of this pilot study was to investigate the potential of early-phase single-photon emission computed tomography (SPECT)/computed tomography (CT) using technetium-99m methyl diphosphonate (99mTc-MDP) for diagnosing osteomyelitis (OM). MATERIALS AND METHODS: Twenty-one patients with suspected OM were enrolled retrospectively. Three-phase bone scan (TPBS), early-phase SPECT/CT (immediately after blood pool planar imaging), and delayed-phase SPECT/CT (immediately after delayed planar imaging) were performed. The final diagnoses were established through surgery or clinical follow-up for over 6 months. We compared three diagnostic criteria based on (I) TPBS alone, (II) combined TPBS and delayed-phase SPECT/CT, and (III) early-phase SPECT/CT alone. RESULTS: OM was diagnosed in 11 of 21 patients (nine surgically and two clinically). Of the 11 OM patients, criterion-I, criterion-II, and criterion-III were positive in six, seven, and 10 patients, respectively. Of the 10 non-OM patients, criterion-I, criterion-II, and criterion-III were negative in five, five, and seven patients, respectively. The sensitivity/specificity/accuracy of criterion-I, criterion-II, and criterion-III for diagnosing OM were 54.5%/50.0%/55.0%, 63.6%/50.0%/57.1%, and 90.9%/70.0%/87.5%, respectively. CONCLUSION: This pilot study demonstrated the potential of using the early-phase SPECT/CT to diagnose OM. Based on the results, prospective studies with a larger sample size should be conducted to confirm the efficacy of early-phase SPECT/CT.

Antagonistic interaction between central glucagon-like Peptide-1 and oxytocin on diet-induced obesity mice.

Glucagon-like peptide-1 (GLP-1), whose agonists are widely prescribed, is a peptide proven effective in reducing obesity. Similarly, oxytocin (OXT) is a peptide known to increase satiety and help reduce body weight. In the present study, we aimed to examine the metabolic effects of co-administration of GLP-1 and OXT in diet-induced obesity (DIO) mice to elucidate their functions and interactions in the central nervous system. To this end, 40 DIO mice were subjected to stereotaxic surgery for the installation of an osmotic minipump and intracerebroventricular administration of GLP-1, OXT, or both. Initially, it was anticipated that co-administration of these anorexigenic peptides would be as effective as, if not more than, either GLP-1 or OXT alone in providing metabolic benefits to the obese mice. Interestingly, co-administration of OXT and GLP-1 offset the reductions in body weight and food intake promoted by either peptide alone. Co-administration also negated the decrease in fat and increase in lean mass produced by either peptide alone. Moreover, co-administration showed an equivalent calorimetric benefit as either peptide alone. Therefore, these results suggest antagonistic, rather than synergistic or additive, effects of centrally administered GLP-1 and OXT that attenuate the metabolic benefits of either peptide.

Glucagon-Like Peptide-1 Receptor Agonist Differentially Affects Brain Activation in Response to Visual Food Cues in Lean and Obese Individuals with Type 2 Diabetes Mellitus.

BACKGROUND: To investigate the effects of a glucagon-like peptide-1 receptor agonist on functional brain activation in lean and obese individuals with type 2 diabetes mellitus (T2DM) in response to visual food cues. METHODS: In a randomized, single-blinded, crossover study, 15 lean and 14 obese individuals with T2DM were administered lixisenatide or normal saline subcutaneously with a 1-week washout period. We evaluated brain activation in response to pictures of high-calorie food, low-calorie food, and nonfood using functional magnetic resonance imaging and measured appetite and caloric intake in participants who were given access to an ad libitum buffet. RESULTS: Obese individuals with T2DM showed significantly greater activation of the hypothalamus, pineal gland, parietal cortex (high-calorie food vs. low-calorie food, P<0.05), orbitofrontal cortex (high-calorie food vs. nonfood, P<0.05), and visual cortex (food vs. nonfood, P<0.05) than lean individuals with T2DM. Lixisenatide injection significantly reduced the functional activation of the fusiform gyrus and lateral ventricle in obese individuals with T2DM compared with that in lean individuals with T2DM (nonfood vs. high-calorie food, P<0.05). In addition, in individuals who decreased their caloric intake after lixisenatide injection, there were significant interaction effects between group and treatment in the posterior cingulate, medial frontal cortex (high-calorie food vs. low-calorie food, P<0.05), hypothalamus, orbitofrontal cortex, and temporal lobe (food vs. nonfood, P<0.05). CONCLUSION: Brain responses to visual food cues were different in lean and obese individuals with T2DM. In addition, acute administration of lixisenatide differentially affected functional brain activation in these individuals, especially in those who decreased their caloric intake after lixisenatide injection.

Chemogenetic manipulation of parasympathetic neurons (DMV) regulates feeding behavior and energy metabolism.

Parasympathetic nervous system (PNS) innervates with several peripheral organs such as liver, pancreas and regulates energy metabolism. However, the direct role of PNS on food intake has been poorly understood. In the present study, we investigated the role of parasympathetic nervous system in regulation of feeding by chemogenetic methods. Adeno associated virus carrying DREADD (designer receptors exclusively activated by designer drugs) infused into the target brain region by stereotaxic surgery. The stimulatory hM3Dq or inhibitory hM4Di DREADD was over-expressed in selective population of dorsal motor nucleus of the vagus (DMV) neurons by Cre-recombinase-dependent manners. Activation of parasympathetic neuron by intraperitoneal injection of the M3-muscarinic receptor ligand clozapine-N-oxide (CNO) (1 mg/kg) suppressed food intake and resulted in body weight loss in ChAT-Cre mice. Parasympathetic neurons activation resulted in improved glucose tolerance while inhibition of the neurons resulted in impaired glucose tolerance. Stimulation of parasympathetic nervous system by injection of CNO (1 mg/kg) increased oxygen consumption and energy expenditure. Within the hypothalamus, in the arcuate nucleus (ARC) changed AGRP/POMC neurons. These results suggest that direct activation of parasympathetic nervous system decreases food intake and body weight with improved glucose tolerance.

Genetic analysis of parathyroid and pancreatic tumors in a patient with multiple endocrine neoplasia type 1 using whole-exome sequencing.

BACKGROUND: Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant hereditary disorder characterized by the presence of endocrine tumors affecting the parathyroid, pancreas, and pituitary. A heterozygous germline inactivating mutation in the MEN1 gene (first hit) may be followed by somatic loss of the remaining normal copy or somatic mutations in the MEN1 gene (second hit). Whole-exome sequencing has been successfully used to elucidate the mutations associated with the different types of tumors. CASE PRESENTATION: We performed whole-exome sequencing (WES) on three parathyroid tumors, one pancreatic insulinoma, and a blood sample taken from the same patient with MEN1 to study tumor heterogeneity in MEN1 originating from different tumors. We identified a novel frame-shift deletion (c.1382_1383delAG, p.E461GfsX69) in the MEN1 gene using WES, which was confirmed by Sanger sequencing. WES and the SNP array revealed somatic LOH on chromosome 11 in parathyroid tumors (left upper, left lower, and right upper parathyroid). However, we did not detect a somatic MEN1 gene mutation or LOH in the pancreatic insulinoma. WES revealed two somatic functional variants outside the MEN1 gene in the pancreatic insulinoma. CONCLUSIONS: This study revealed heterogeneity among tumors in the same patient with MEN1, suggesting that different tumor-specific tumorigenic mechanisms may contribute to the pathogenesis of MEN1 tumors. The present study supports the clinical applicability of the WES strategy to research on multiple tumor samples and blood.

Central administration of GLP-1 and GIP decreases feeding in mice.

Glucagon-like peptide-1 amide (GLP-1) and gastric inhibitory polypeptide (GIP) are incretin hormones regulating energy metabolism. GLP-1 and GIP combination is suggested as a promising therapeutic strategy for treatment of obesity and diabetes. However, the neuronal mechanisms are not yet investigated. In the present study, we investigated the role of central GLP-1 and GIP in regulation of body weight homeostasis. The effect of GLP-1 with GIP on food intake, body weight, locomotor activity were determined following intracerebroventricular (ICV) administration of GLP-1 and/or GIP in mice. ICV administration of low dose GLP-1 (0.3 nmol) and GIP (1 and 3 nmol) did not change food intake. However, ICV administration of higher doses GLP-1 (1 and 3 nmol) and GIP (6 nmol) significantly decreased food intake and body weight. To investigate the synergic effect of ICV GLP-1 and GIP, subeffective dose GLP-1 (0.3 nmol) and subeffective dose GIP (1 nmol) were chosen for further co-administration study. ICV co-administration of GLP-1 and GIP significantly decreased food intake, body weight and drinking. ICV co-administration of GLP-1 and GIP significantly increased neuronal activation and pro-opiomelanocortin (POMC) expression in hypothalamic arcuate nucleus. The neuronal activation and POMC expression were observed in two distinct neuronal populations. These results provide neuronal mechanisms supporting the development of GLP-1 and GIP combination therapeutics for treatment of obesity and diabetes.

Association between metformin use and mortality in patients with type 2 diabetes mellitus and localized resectable pancreatic cancer: a nationwide population-based study in korea.

BACKGROUND: Preclinical studies support an antitumor effect of metformin. However, clinical studies have conflicting results and metformin's effect remains controversial. The aim of this study was to evaluate metformin's effect on clinical outcomes in diabetic patients with pancreatic cancer treated with curative resection. RESULTS: A total of 764 patients underwent curative resection, met none of the exclusion criteria, and were prescribed oral hypoglycemic agents. The cancer-specific survival (5-year, 31.9% vs. 22.2%, p < 0.001) was significantly higher in the 530 metformin users than in the 234 diabetic metformin non-users. After multivariable adjustments, metformin users had significantly lower cancer-specific mortality as compared with metformin non-users (hazard ratio, 0.727; 95% confidence interval, 0.611-0.868). Cubic spline regression analysis demonstrated significantly decreased cancer-specific mortality with increasing dose of metformin (p = 0.0047). MATERIALS AND METHODS: Data were provided from the Korea Central Cancer Registry and the National Health Insurance Service in the Republic of Korea. The study cohort consisted of 28,862 patients newly diagnosed with pancreatic cancer between 2005 and 2011. Metformin exposure was determined from prescription information from 6 months before the first diagnosis of pancreatic cancer to last follow-up. The main outcome was cancer-specific survival. CONCLUSIONS: This large study indicates that metformin might decrease cancer-specific mortality rates in localized resectable pancreatic cancer patients with pre-existing diabetes, independently of other factors, with a dose-response relationship.

Association of Metformin Use With Cancer-Specific Mortality in Hepatocellular Carcinoma After Curative Resection: A Nationwide Population-Based Study.

Many preclinical reports and retrospective population studies have shown an anticancer effect of metformin in patients with several types of cancer and comorbid type 2 diabetes mellitus (T2DM). In this work, the anticancer effect of metformin was assessed in hepatocellular carcinoma (HCC) patients with T2DM who underwent curative resection.A population-based retrospective cohort design was used. Data were obtained from the National Health Insurance Service and Korea Center Cancer Registry in the Republic of Korea, identifying 5494 patients with newly diagnosed HCC who underwent curative resection between 2005 and 2011. Crude and adjusted hazard ratios (HRs) were calculated using Cox proportional hazard models to estimate effects. In the sensitivity analysis, we excluded patients who started metformin or other oral hypoglycemic agents (OHAs) after HCC diagnosis to control for immortal time bias.From the patient cohort, 751 diabetic patients who were prescribed an OHA were analyzed for HCC-specific mortality and retreatment upon recurrence, comparing 533 patients treated with metformin to 218 patients treated without metformin. In the fully adjusted analyses, metformin users showed a significantly lower risk of HCC-specific mortality (HR 0.38, 95% confidence interval [CI] 0.30-0.49) and retreatment events (HR 0.41, 95% CI 0.33-0.52) compared with metformin nonusers. Risks for HCC-specific mortality were consistently lower among metformin-using groups, excluding patients who started metformin or OHAs after diagnosis.In this large population-based cohort of patients with comorbid HCC and T2DM, treated with curative hepatic resection, metformin use was associated with improvement of HCC-specific mortality and reduced occurrence of retreatment events.

Incidence of permanent hypocalcaemia after total thyroidectomy with or without central neck dissection for thyroid carcinoma: a nationwide claim study.

OBJECTIVE: Permanent hypocalcaemia is the most common and serious complication after total thyroidectomy (TT). This study examined the impact of central neck dissection (CND) and institutional volume on rates of permanent hypocalcaemia by analysing data held in the nationwide claim database of South Korea. DESIGN: Data from patients who underwent TT due to thyroid carcinoma from 2007-2013 were obtained from the Health Insurance Review and Assessment Service database. Of these, patients prescribed more than 1000 mg of elemental calcium for more than 288 days during the first 360 days postsurgery were defined as having permanent hypocalcaemia. RESULTS: In total, 192 333 patients (32 988 male and 159 345 female) were eligible for analysis. Of these, 52 707 (27·4%) underwent TT alone and 139 626 (72·6%) underwent TT plus CND. The incidence of permanent hypocalcaemia was greater in the TT plus CND group than in the TT alone group (5·4% vs 4·6%, P < 0·001). The age- and sex-adjusted risk for permanent hypocalcaemia in the TT plus CND group was 1·20 (P < 0·001). CND did not raise the rates of permanent hypocalcaemia in institutes with a low volume of annual cases (<200), whereas permanent hypocalcaemia was more common in the TT plus CND group than in the TT alone group (3·5% vs 2·9%, P = 0·002) in institutes with a large volume of annual cases (≥800). CONCLUSIONS: TT plus CND was associated with a greater risk of permanent hypocalcaemia than TT alone. Surgeons should consider the risk of permanent hypocalcaemia when deciding whether to perform CND.

Osteoporotic Fracture Risk Assessment Using Bone Mineral Density in Korean: A Community-based Cohort Study.

BACKGROUND: Fracture-risk assessment tool (FRAX) using just clinical risk factors of osteoporosis has been developed to estimate individual risk of osteoporotic fractures. We developed prediction model of fracture risk using bone mineral density (BMD) as well as clinical risk factors in Korean, and assessed the validity of the final model. METHODS: To develop and validate an osteoporotic FRAX, a total of 768 Korean men and women aged 50 to 90 years were followed for 7 years in a community-based cohort study. BMD as well as clinical risk factors for osteoporotic fracture including age, sex, body mass index, history of fragility fracture, family history of fracture, smoking status, alcohol intake, use of oral glucocorticoid, rheumatoid arthritis, and other causes of secondary osteoporosis were assessed biannually. RESULTS: During the follow-up period, 86 osteoporotic fractures identified (36 in men and 50 in women). The developed prediction models showed high discriminatory power and had goodness of fit. CONCLUSIONS: The developed a Korean specific prediction model for osteoporotic fractures can be easily used as a screening tool to identify individual with high risk of osteoporotic fracture. Further studies for validation are required to confirm the clinical feasibility in general Korean population.