Long-term Cardiovascular Risks of Gonadotropin-releasing Hormone Agonists and Antagonists: A Population-based Cohort Study.

AIMS: Gonadotropin-releasing hormone (GnRH) agonists and antagonists, critical medications for prostate cancer (PCa) treatment, may differ in cardiovascular safety. This prospective cohort study aimed to compare the long-term cardiovascular risks between GnRH agonists and antagonists. MATERIALS AND METHODS: Patients with PCa receiving GnRH agonists or antagonists during 2013-2021 in Hong Kong were identified. Patients with <6 months' prescriptions, who were switching between drugs, had missing baseline prostate-specific antigen level or had a prior stroke or myocardial infarction were excluded. Patients were followed up until September 2021. The primary outcome was major adverse cardiovascular events (MACE) as in the PRONOUNCE trial (MACEPRONOUNCE), i.e. a composite of all-cause mortality, stroke and myocardial infarction. The secondary outcome was MACECVM, i.e. a composite of cardiovascular mortality, stroke and myocardial infarction. Inverse probability treatment weighting was used to balance covariates between groups. The Log-rank test was used to compare the cumulative freedom from the primary outcome between groups. RESULTS: In total, 2479 patients were analysed (162 GnRH antagonist users and 2317 agonist users; median age 75.0 years, interquartile range 68.0-81.6 years). Inverse probability treatment weighting achieved good covariate balance between groups. Over a median follow-up duration of 3.0 years (interquartile range 1.7-5.0 years), 1115 patients (45.0%) had MACEPRONOUNCE and 344 (13.9%) had MACECVM. GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.027). However, no differences were observed within 1 year of follow-up (MACEPRONOUNCE: Log-rank P = 0.308; MACECVM: Log-rank P = 0.357). Among patients without cardiovascular risk factors at baseline, GnRH agonist users had lower risks of MACEPRONOUNCE (Log-rank P < 0.001) and MACECVM (Log-rank P = 0.001), whereas no differences were observed in those with such risk factor(s) (MACEPRONOUNCE: Log-rank P = 0.569; MACECVM: Log-rank P = 0.615). CONCLUSIONS: GnRH antagonists may be associated with higher long-term, but not short-term, cardiovascular risks than agonists in Asian patients with PCa, particularly in those without known cardiovascular risk factors.

Live-streaming otolaryngology surgical procedures for virtual medical student rotations.

BACKGROUND: The coronavirus disease 2019 pandemic created challenges in surgical education that expedited the development of virtual learning. Virtual rotations have been one such solution. However, they require co-ordination and technological equipment to create a meaningful, interactive experience for students. METHODS: Various otolaryngology surgical procedures were live-streamed during a two-week virtual rotation for medical students. A mobile audiovisual cart comprising a computer mounted with a webcam and microphone/speaker were utilised to live-stream from four sources: video-assisted telescope operating monitor ('VITOM') exoscope, microscope, endoscope and room camera. A dedicated faculty member, who was not the operating surgeon, was present to facilitate students' understanding of the procedure. CONCLUSION: A wide breadth of otolaryngology surgical procedures were live-streamed via a mobile audiovisual computer, including views of the room, endoscopic views, microscopic views and open views via an exoscope (video-assisted telescope operating monitor). This virtual rotation set-up, along with the dedicated faculty facilitator, reduced the burden on the operating surgeon and enhanced students' learning experience.

[Melatonin Induces Apoptotic Cell Death in 3T3-L1 Preadipocytes].

Obesity is a major disease that causes significant complications. Inhibition of preadipocyte proliferation has the potential to prevent obesity and metabolic diseases. Melatonin is a pineal gland hormone that has various effects on cells and tissues. In this research, we investigated whether melatonin induces apoptosis in 3T3-L1 preadipocytes. 3T3-L1 preadipocytes were cultured until confluence and then treated with 0, 10, 100, and 1000 µM melatonin for 1, 3, and 5 days. A cell viability assay kit was used for determining cell viability. Cell death marker proteins were assessed by Western blot analysis using GAPDH for control. Apoptotic morphological changes with nuclei fragmentation were observed using DAPI staining. Melatonin treatment decreased the phosphorylated extracellular signal-regulated kinases (p-ERK) activation while increasing the activation of caspase-3, 8, and 9. Furthermore, melatonin not only increased Bcl-2-associated X protein (Bax) but decreased B-cell lymphoma 2 (Bcl-2) expression as dose increases from 0 to 1000 µM. The melatonin treatment also suppressed the growth of preadipocytes with increasing concentration. These effects were attenuated by luzindole, a melatonin receptor antagonist and U0126, an inhibitor of p-ERK activation. In conclusion, melatonin can induce apoptosis of 3T3-L1 preadipocytes via p-ERK decrease.

The proliferative phase endometrium in IVF/ICSI: an in-cycle molecular analysis predictive of the outcome following fresh embryo transfer.

STUDY QUESTION: Does an early proliferative phase endometrial biopsy harvested during ovarian stimulation harbour information predictive of the outcome following fresh embryo transfer (ET) in that same cycle? SUMMARY ANSWER: Transcriptome analysis of the whole-tissue endometrium did not reveal significant differential gene expression (DGE) in relation to the outcome; however, the secretome profile of isolated, cultured and in vitro decidualized endometrial stromal cells (EnSCs) varied significantly between patients who had a live birth compared to those with an implantation failure following fresh ET in the same cycle as the biopsy. WHAT IS KNOWN ALREADY: In the majority of endometrial receptivity research protocols, biopsies are harvested during the window of implantation (WOI). This, however, precludes ET in that same cycle, which is preferable as the endometrium has been shown to adapt over time. Endometrial biopsies taken during ovarian stimulation have been reported not to harm the chances of implantation, and in such biopsies DGE has been observed between women who achieve pregnancy versus those who do not. The impact of the endometrial proliferative phase on human embryo implantation remains unclear, but deserves further attention, especially since in luteal phase endometrial biopsies, a transcriptional signature predictive for repeated implantation failure has been associated with reduced cell proliferation, possibly indicating proliferative phase involvement. Isolation, culture and in vitro decidualization (IVD) of EnSCs is a frequently applied basic research technique to assess endometrial functioning, and a disordered EnSC secretome has previously been linked with failed implantation. STUDY DESIGN, SIZE, DURATION: This study was nested in a randomized controlled trial (RCT) investigating the effect of endometrial scratching during the early follicular phase of ovarian stimulation on clinical pregnancy rates after IVF/ICSI. Of the 96 endometrial biopsies available, after eliminating those without fresh ET and after extensive matching in order to minimize the risk of potential confounding, 18 samples were retained to study two clinical groups: nine biopsies of patients with a live birth versus nine biopsies of patients with an implantation failure, both following fresh ET performed in the same cycle as the biopsy. We studied the proliferative endometrium by analysing its transcriptome and by isolating, culturing and decidualizing EnSCs in vitro. We applied this latter technique for the first time on proliferative endometrial biopsies obtained during ovarian stimulation for in-cycle outcome prediction, in an attempt to overcome inter-cycle variability. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA-sequencing was performed for 18 individual whole-tissue endometrial biopsies on an Illumina HiSeq1500 machine. DGE was analysed three times using different approaches (DESeq2, EdgeR and the Wilcoxon rank-sum test, all in R). EnSC isolation and IVD was performed (for 2 and 4 days) for a subset of nine samples, after which media from undifferentiated and decidualized cultures were harvested, stored at -80°C and later assayed for 45 cytokines using a multiplex suspension bead immunoassay. The analysis was performed by partial least squares regression modelling. MAIN RESULTS AND THE ROLE OF CHANCE: After correction for multiple hypothesis testing, DGE analysis revealed no significant differences between endometrial samples from patients who had a live birth and those with an implantation failure following fresh ET. However secretome analysis after EnSC isolation and culture, showed two distinct clusters that clearly corresponded to the two clinical groups. Upon IVD, the secretome profiles shifted from that of undifferentiated cells but the difference between the two clinical groups remained yet were muted, suggesting convergence of cytokine profiles after decidualization. LIMITATIONS, REASONS FOR CAUTION: Caution is warranted due to the limited sample size of the study and the in vitro nature of the EnSC experiment. Validation on a larger scale is necessary, however, hard to fulfil given the very limited availability of in-cycle proliferative endometrial biopsies outside a RCT setting. WIDER IMPLICATIONS OF THE FINDINGS: These data support the hypothesis that the endometrium should be assessed not only during the WOI and that certain endometrial dysfunctionalities can probably be detected early in a cycle by making use of the proliferative phase. This insight opens new horizons for the development of endometrial tests, whether diagnostic or predictive of IVF/ICSI treatment outcome. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Fonds Wetenschappelijk Onderzoek (FWO, Flanders, Belgium, 11M9415N, 1 524 417N), Wetenschappelijk Fonds Willy Gepts (WFWG G160, Universitair Ziekenhuis Brussel, Belgium) and the National Medicine Research Council (NMRC/CG/M003/2017, Singapore). There are no conflicts of interests. TRIAL REGISTRATION NUMBER: NCT02061228.

Effects of hydrochlorothiazide on drainage volume and seroma formation in deep inferior epigastric perforator flap breast reconstruction: Randomized controlled trial.

BACKGROUND: Seroma is a recognized complication encountered at the reconstructed breast and donor site after abdominal-based breast reconstruction. Seroma is caused by lymphatic channel disruption and the formation of a large space between the deep fascia during flap elevation. Surgical techniques to preserve the lymphatics and secure the closure of the donor site can reduce seroma formation. This study investigated the safety and effectiveness of the diuretic hydrochlorothiazide at reducing interstitial fluid accumulation and seroma formation during deep inferior epigastric perforator (DIEP) flap breast reconstruction. METHODS: Sixty patients with breast cancer who underwent skin- or nipple-sparing mastectomy and DIEP flap reconstruction were enrolled between August 2016 and June 2017. The patients were randomly assigned to receive either 25 mg per day of hydrochlorothiazide from the second to the twentieth day after surgery (treatment) or no diuretic (control). The clinicopathological characteristics, drainage time, and drainage volume were statistically compared between the two groups. RESULTS: The average total drainage volume at the donor site was 291 mL in the treatment group and 434 mL in the control group (p = 0.003). The differences in body mass index and flap weight between the two groups were not statistically significant (p = 0.879 and p = 0.963, respectively). No hypotension or electrolyte imbalance was noted during the follow-up. CONCLUSIONS: Intake of 25 mg per day of hydrochlorothiazide tablets effectively reduced the total abdominal drainage volume and removal time of indwelling drains. However, the adverse effects should be further investigated in a large population and multiracial cohort before using hydrochlorothiazide for seroma prevention.

Association between CD40 polymorphisms and systemic lupus erythematosus and correlation between soluble CD40 and CD40 ligand levels in the disease: a meta-analysis.

OBJECTIVE: The aim of this study was to systematically review evidence regarding the association between CD40 polymorphisms and systemic lupus erythematosus and between soluble CD40 (sCD40) and CD40 ligand (sCD40L) levels and systemic lupus erythematosus. METHODS: We performed a meta-analysis on the association between CD40 rs4810495, rs1883832, and rs376545 polymorphisms and systemic lupus erythematosus risk and sCD40/sCD40L levels in patients with systemic lupus erythematosus and controls. RESULTS: Fourteen studies were included. Ethnicity-specific meta-analysis indicated a significant association between the T allele of CD40 rs4810485 polymorphism and systemic lupus erythematosus in Europeans (odds ratio = 0.715, 95% confidence interval = 0.641-0.832, p < 0.001) and a trend toward an association between the T allele and systemic lupus erythematosus in Asians (odds ratio = 1.255, 95% confidence interval = 0.978-1.810, p = 0.074). Furthermore, a significant association was reported between systemic lupus erythematosus and the C allele of CD40 rs1883832 polymorphism (odds ratio = 1.235, 95% confidence interval = 1.087-1.405, p = 0.001) and A allele of CD40 rs3765456 polymorphism and systemic lupus erythematosus in Asians (odds ratio = 1.184, 95% confidence interval = 1.040-1.348, p = 0.011). sCD40 and sCD40L levels were significantly higher in SLE than in controls (standardized mean difference = 1.564, 95% confidence interval = 0.256-2.872, p = 0.019 and standardized mean difference = 1.499, 95% confidence interval = 1.031-1.967, p < 0.001, respectively). Stratification based on ethnicity revealed higher sCD40L levels in the systemic lupus erythematosus group among European, Asian, North American, and Arab populations. CONCLUSIONS: Our meta-analyses found associations between CD40 rs4810495, rs1883832, and rs376545 polymorphisms and systemic lupus erythematosus susceptibility and significantly higher sCD40 and sCD40L levels in patients with systemic lupus erythematosus than in controls.

Routine chest CT for staging of gastric cancer.

BACKGROUND: International guidelines on clinical staging of gastric cancer recommend the use of chest CT for the detection of pulmonary metastases. This study assessed the clinical value of routine chest CT in the staging of gastric cancer. METHODS: This retrospective study included patients identified from the gastric cancer registry of Chang Gung Memorial Hospital, Linkou, Taiwan. All patients who underwent clinical staging between 2008 and 2014 were included. The pattern, site and number of metastases at initial presentation and after surgery with curative intent were evaluated. Pulmonary metastases were defined as multiple small round pulmonary nodules with a random distribution or of variable size. RESULTS: Some 1669 patients were included, of whom 478 (28·6 per cent) had metastatic disease at clinical presentation. The majority of metastases were to the peritoneum (75·7 per cent of patients) or liver (30·5 per cent), and only 27 patients (5·6 per cent) had pulmonary metastases at presentation, none of which were isolated to the lung. Of these 27 patients, 11 had primary lesions located at the cardia/fundus. In 19 patients the lung metastases were also detected on the staging chest X-ray. After surgery there were 196 cancer recurrences. Some 15 patients (7·6 per cent) had lung metastasis and this was not the only site of metastases in any patient. The prevalence of lung metastasis at presentation of the disease and after surgery was 1·6 and 1·5 per cent respectively. CONCLUSION: This study does not support the routine use of chest CT for staging of gastric cancer as isolated pulmonary metastasis in the absence of other metastatic sites could not be detected.

Phase lag entropy as a hypnotic depth indicator during propofol sedation.

Phase lag entropy, an electro-encephalography-based hypnotic depth indicator, calculates diversity in temporal patterns of phase relationship. We compared the performance of phase lag entropy with the bispectral index™ in 30 patients scheduled for elective surgery. We initiated a target-controlled infusion of propofol using the Schnider model, and assessed sedation levels using the Modified Observer's Assessment of Alertness/Sedation scale every 30 s with each stepwise increase in the effect-site propofol concentration. Phase lag entropy and bispectral index values were recorded. The correlation coefficient and prediction probability between phase lag entropy or bispectral index and the sedation level or effect-site propofol concentration were analysed. We calculated baseline variabilities of phase lag entropy and bispectral index. In addition, we applied a non-linear mixed-effects model to obtain the pharmacodynamic relationships among the effect-site propofol concentration, phase lag entropy or bispectral index and sedation level. As sedation increased, phase lag entropy and bispectral index both decreased. The prediction probability values of phase lag entropy and bispectral index for sedation levels were 0.697 and 0.700 (p = 0.261) and for the effect-site concentration of propofol were 0.646 and 0.630 (p = 0.091), respectively. Baseline variability in phase lag entropy and bispectral index was 3.3 and 5.7, respectively. The predicted propofol concentrations, using the Schnider pharmacokinetic model, producing a 50% probability of moderate and deep sedation were 1.96 and 3.01 µg.ml-1 , respectively. Phase lag entropy was found to be useful as a hypnotic depth indicator in patients receiving propofol sedation.

Overall and cause-specific mortality in giant cell arteritis : A meta-analysis.

OBJECTIVE: This study aimed to assess the all-cause and cause-specific standardized mortality ratios (SMRs) in patients with giant cell arteritis (GCA). METHODS: We surveyed studies examining all-cause and/or cause-specific SMRs in patients with GCA compared to the general population, using MEDLINE, EMBASE, Cochrane databases, and manual searches. We then performed a meta-analysis of all-cause, sex-specific, region-specific, and cause-specific SMRs in patients with GCA. RESULTS: In total, 8 reports including 1972 patients with GCA (including 877 patients who died) met the inclusion criteria. Compared with the general population, all-cause SMR was not increased in patients with GCA (SMR 1.081, 95% confidence interval [CI] 0.963-1.214, p = 0.184). Stratification by region showed no significant increase in all-cause SMR in Europe and USA. Sex-specific meta-analysis revealed that the pooled SMR was 1.046 (95%CI 0.834-1.314, p = 0.696) for women and 1.051 (95%CI 0.974-1.133, p = 0.204) for men. There were no sex-specific significant differences in SMR. The risk of mortality due to cardiovascular disease (CVD) was significantly increased (SMR 1.312, 95%CI 1.136-1.516, p < 0.001). However, there was no significant increase in the SMR for mortality due to cancer (SMR 0.833, 95%CI 0.613-1.132, p = 0.243). CONCLUSIONS: Patients with GCA do not show increased rates of death from all causes, regardless of sex, region, or malignancy. However, these patients are at an increased risk of death due to CVD.

Association of circulating resistin, leptin, adiponectin and visfatin levels with Behçet disease: a meta-analysis.

BACKGROUND: Behçet disease (BD) is a chronic inflammatory disease. Adipokines are synthesized in adipose tissue, and have been reported to play important roles in the pathogenesis of autoimmune and inflammatory diseases, including BD. AIM: To evaluate the relationship between circulating blood adipokine levels and BD. METHODS: We conducted a meta-analysis of papers reporting on serum/plasma resistin, leptin, adiponectin and visfatin levels in patients with BD and in healthy controls (HCs). We identified 82 relevant studies using electronic and manual search methods, and selected 16 studies for full-text review based on the title and abstract. Two of these were later excluded (one was a review, one had no data), leaving 14 articles that met the inclusion criteria for this meta-analysis. RESULTS: The 14 included studies assessed 637 patients with BD and 520 HCs. Compared with the HCs, the BD group had significantly higher levels of leptin [standardized mean difference (SMD) = 0.68, 95% CI 0.15-1.21, P = 0.01]. Levels of resistin (SMD = 0.51, 95% CI 0.92-0.918, P = 0.02) and adiponectin (SMD = 0.31, 95% CI 0.06-0.56, P = 0.02) were significantly higher in the BD group after adjustment for age, sex and body mass index (BMI), but not without such adjustment (resistin: (SMD = 0.38, 95% CI -0.18 to 0.93, P = 0.19; adiponectin: SMD = -0.59, 95% CI -2.23 to 1.06, P = 0.48). A significantly lower visfatin level was found in the BD group with adjustment (SMD = -1.70, 95% CI -2.14 to -1.25, P < 0.001) but not without adjustment (SMD = 0.31, 95% CI -0.21 to 0.82, P = 0.24). CONCLUSIONS: Our meta-analysis revealed significantly higher circulating resistin, leptin and adiponectin levels and lower visfatin levels in patients with BD than in HCs, indicating that adipokines probably play an important role in BD pathogenesis.

Anti-inflammatory and antioxidant properties of Schisandrin C promote mitochondrial biogenesis in human dental pulp cells.

AIM: To examine the properties of Schisandrin C as an anti-inflammatory and antioxidant compound, and whether its characteristics promote mitochondrial biogenesis in human dental pulp cells (HDPCs). METHODOLOGY: HDPCs were extracted from fresh third molars and cultured for experiments. Reactive oxidative stress (ROS) and nitric oxide (NO) formation were analysed by a Muse cell analyser. Western blotting and gelatin zymography were used to identify the presence of antioxidants, as well as anti-inflammatory and mitochondrial biogenesis with specific antibody. An unpaired Student's t-test was used for statistical analysis. RESULTS: Schisandrin C inhibited lipopolysaccharide-stimulated inflammatory molecules; interleukin 1 beta, tumour necrosis factor alpha, intracellular adhesion molecule-1, vascular cell adhesion molecule-1, matrix metalloproteinase-2 and -9, NO production, ROS formation, nuclear factor kappa B translocation (P < 0.05) through the mitogen-activated protein kinase pathway. Schisandrin C increased the expression of superoxide dismutase enzymes as well as haem oxygenase-1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha through the phosphorylated-protein kinase B (p-Akt) and nuclear factor erythroid 2-related factor-2 pathways (P < 0.05). The anti-inflammatory and antioxidant properties of Schisandrin C promoted mitochondrial biogenesis. CONCLUSIONS: Schisandrin C has the potential to reduce inflammation and oxidation and to promote mitochondrial biogenesis. Therefore, Schisandrin C may be considered for use as an anti-inflammatory compound for oral inflammation through mitochondrial biogenesis.

Relative efficacy and safety of apremilast, secukinumab, and ustekinumab for the treatment of psoriatic arthritis.

OBJECTIVE: To assess the relative efficacy and safety of apremilast, secukinumab, and ustekinumab at different doses in patients with active psoriatic arthritis (PsA). METHOD: A Bayesian network meta-analysis was conducted, which included randomized controlled trials (RCTs) that examined the efficacy and safety of apremilast 20 mg, apremilast 30 mg, secukinumab 75 mg, secukinumab 150 mg, secukinumab 300 mg, ustekinumab 45 mg, and ustekinumab 90 mg compared with placebo. RESULTS: Of the RCTs 8 comprising 3289 patients met the inclusion criteria. The American College of Rheumatology (ACR) 20 response rate was significantly higher in the secukinumab 300 mg group than in the placebo group (odds ratio OR, 7.55; 95% confidence interval CI, 3.18-17.63). Secukinumab 150 mg, secukinumab 75 mg, ustekinumab 90 mg, apremilast 30 mg, apremilast 20 mg, and ustekinumab 45 mg were also more efficacious than placebo. There were no significant differences in the efficacy between the interventions. A dose-response relationship among the same drug groups was observed. The number of serious adverse events was not significantly different among the apremilast, secukinumab, ustekinumab, and placebo groups. CONCLUSION: All drug treatments were more efficacious than placebo; however, there were no significant differences in the efficacy and safety between the drugs at the different doses.

The severity of periodontitis and metabolic syndrome in Korean population: The Dong-gu study.

OBJECTIVES: We assessed the association between periodontal disease status and metabolic syndrome (MetS) and its individual components in Korean adults over 50 years old. MATERIAL AND METHODS: In the Dong-gu study, 5078 men and women aged over 50 years were included. They underwent a questionnaire survey, physical assessment, biochemical assessment and periodontal assessment. The percentages of sites with periodontal probing depth ≥4 mm, and clinical attachment loss ≥4 mm were recorded for each participant. Periodontal disease was also classified by the Centers for Disease Control and Prevention/American Academy of Periodontology definition of periodontitis and the American Academy of Periodontology definition (1999). MetS was defined by the 2009 guidelines of the International Diabetes Federation. This study used multivariate negative binominal regression analysis to assess the association between the severity of periodontitis and MetS, after age, smoking habits, alcohol consumption and physical activity related factors were adjusted for. RESULTS: Prevalence of MetS was 32.3%, 36.2% and 45.9% among men with no or mild, moderate and severe periodontitis, respectively. The severity of periodontitis was positively associated with the prevalent MetS in men but not in women. In men, severe periodontitis showed a higher risk of MetS than those with no or mild periodontitis (relative risk 1.43, 95% confidence interval 1.17-1.73) after adjusting for confounders. Periodontal probing depth was positively associated with the prevalence of MetS in both genders. In the analysis separated by individual MetS components, periodontitis severity was positively associated with hypertriglyceridemia and low high-density lipoprotein cholesterol in men, while positively associated with low high-density lipoprotein cholesterol and abdominal obesity in women. CONCLUSION: Increasing the severity of periodontitis was associated with the risk of prevalent MetS in Korean adults. This result confirmed that periodontal inflammation might be a contributive factor of MetS.

Dietary total, animal, vegetable calcium and type 2 diabetes incidence among Korean adults: The Korean Multi-Rural Communities Cohort (MRCohort).

BACKGROUND AND AIMS: Although a possible mechanism for developing type 2 diabetes in relation to calcium intake has been suggested, there is currently little epidemiological evidence on the association between dietary calcium and type 2 diabetes (T2D). This study aimed to evaluate the prospective association between dietary calcium and T2D incidence among adults 40 years of age or over, from the Multi-rural Communities Cohort (MRCohort), South Korea. METHODS AND RESULTS: In total, 8313 participants (3033 men and 5280 women) who did not have diabetes at baseline were recruited between 2005 and 2013. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. During follow-up (31,570 person-years), 322 T2D cases were newly diagnosed. Dietary calcium (total and vegetable calcium) were inversely associated with the risk of T2D incidence among women (IRR = 0.61, 95% CI = 0.43-0.86, P for trend = 0.007 in third tertile of baseline total calcium intake comparing to the first tertile; IRR = 0.57, 95% CI = 0.39-0.84, P for trend = 0.006 for baseline vegetable calcium intake), not for men. The tendency of those inverse associations remained in both the normal fasting blood glucose group and the impaired fasting blood glucose group and were independent of obesity, smoking, and magnesium intake. CONCLUSIONS: Total and vegetable calcium may be inversely associated with T2D incidence among women, regardless of impaired fasting blood glucose group or normal group. The associations may be potentially dose-responsive. Moderate dietary calcium may be related to lower risk of T2D incidence comparing to low intake group among women.

Predictive performance of the modified Marsh and Schnider models for propofol in underweight patients undergoing general anaesthesia using target-controlled infusion.

BACKGROUND: : In our preliminary study, the modified Marsh (M-Marsh) model caused an inadvertent underdosing of propofol in underweight patients. However, the predictive performance of the M-Marsh and Schnider models incorporated in commercially available target-controlled infusion (TCI) pumps was not evaluated in underweight patients. METHODS: : Thirty underweight patients undergoing elective surgery were randomly allocated to receive propofol via TCI using the M-Marsh or Schnider models. The target effect-site concentrations (Ces) of propofol were, in order, 2.5, 3, 4, 5, 6 and 2 µg ml -1 . Arterial blood samples were obtained at least 7 min after achieving each pseudo-steady-state. RESULTS: A total of 172 plasma samples were used to determine the predictive performance of both models. The pooled median (95% confidence interval) biases and inaccuracies at a target Ce ≤ 3 µg ml -1 were -22.6 (-28.8 to -12.6) and 31.9 (24.8-36.8) for the M-Marsh model and 9.0 (1.7-16.4) and 28.5 (21.7-32.8) for the Schnider model, respectively. These values at Ce ≥ 4 µg ml -1 were -9.6 (-16.0 to -6.0) and 24.7 (21.1-27.9) for the M-Marsh model and 19.8 (12.9-25.7) and 36.2 (31.4-39.7) for the Schnider model, respectively. CONCLUSIONS: The pooled biases and inaccuracies of both models were clinically acceptable. However, the M-Marsh and Schnider models consistently produced negatively and positively biased predictions, respectively, in underweight patients. In particular, the M-Marsh model showed greater inaccuracy at target Ce ≤ 3 µg ml -1 and the Schnider model showed greater inaccuracy at target Ce ≥ 4 µg ml -1 . Therefore, it is necessary to develop a new pharmacokinetic model for propofol in underweight patients. CLINICAL TRIAL REGISTRATION: KCT0001502.

Metastatic carcinoma of the oral region: An analysis of 21 cases.

BACKGROUND: Metastatic carcinoma to the jaws and oral region are very rare, representing less than 1% of all oral tumors. Unfortunately, oral metastasis is usually manifestation of an advanced stage of primary cancer, and indicates widespread disease and poor prognosis. MATERIAL AND METHODS: In this retrospective study, a total of 2039 patients with history of oral malignant tumor between 1980 and 2012 at Seoul National University Dental Hospital were evaluated. We analyzed the dental and medical records, and histopathological database of 2039 patients to assess the prevalence of oral metastasis of carcinoma in terms of sex and age, as well as, the most common origin of primary cancer, and prevalent site and histopathological type of metastatic carcinoma. RESULTS: Among 2039 patients, 21 (1.03%) were finally diagnosed with metastatic carcinoma of the jaws and oral region. Among the 21 patients, only 11 had a working diagnosis as oral metastasis upon clinical evaluation before performing a biopsy. The mean age at the time of diagnosis with a metastatic carcinoma was 56.86, and there was a male preponderance. Metastatic carcinoma was more frequent in the jaws than in the soft tissue, especially in the mandible compared to the maxilla. The most frequent primary site was the lungs, followed by the liver and breasts. The predominant histopathological types were hepatocellular carcinoma and adenocarcinoma. Patient outcomes indicated a poor prognosis with the time from the appearance of the metastasis to death was only 12 months. CONCLUSIONS: According to these cases, oral metastases of carcinoma were exceedingly rare in Koreans. It can allow the clinicians take into account the possible presence of metastases and lead to early diagnosis.