Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

A randomised controlled trial of the analgesia nociception index for intra-operative remifentanil dose and pain after gynaecological laparotomy.

We aimed to investigate the effect of the analgesia nociception index on postoperative pain. We randomly allocated 170 women scheduled for gynaecological laparotomy and analysed results from 159: in 80 women, remifentanil was infused to maintain analgesia nociception indices 50-70; and in 79 women, remifentanil was infused to maintain systolic blood pressure < 120% of baseline values. The primary outcome was the proportion of women with pain scores ≥ 5 (scale 0-10) within 40 min of admission to recovery. The proportion of women with pain scores ≥ 5 was 62/80 (78%) vs. 64/79 (81%), p = 0.73. Mean (SD) doses of fentanyl in recovery were 53.6 (26.9) µg vs. 54.8 (20.8) µg, p = 0.74. Intra-operative remifentanil doses were 0.124 (0.050) µg.kg-1 .min-1 vs. 0.129 (0.044) µg.kg-1 .min-1 , p = 0.55.

Videolaryngoscopy vs. flexible fibrescopy for tracheal intubation in patients with cervical spine immobilisation: a randomised controlled trial.

In patients with cervical spine immobilisation, tracheal intubation devices other than a direct laryngoscope are frequently used to facilitate tracheal intubation and avoid related complications. In this randomised controlled trial, we compared videolaryngoscopic and fibrescopic tracheal intubation in patients with a cervical collar. Tracheal intubation was performed using either a videolaryngoscope with a non-channelled Macintosh blade (n = 166) or a flexible fibrescope (n = 164) in patients having elective cervical spine surgery whose neck was immobilised with a cervical collar to simulate a difficult airway. The primary outcome was the first attempt success rate of tracheal intubation. Secondary outcomes were the overall success rate of tracheal intubation; time to tracheal intubation; use of additional airway manoeuvres; and incidence and severity of tracheal intubation-related airway complications. First attempt success rate was higher in the videolaryngoscope group than in the fibrescope group (164/166 (98.8%) vs. 149/164 (90.9%), p = 0.003). Tracheal intubation was successful within three attempts in all patients. Median (IQR [range]) time to tracheal intubation was shorter (50.0 (41.0-72.0 [25.0-170.0]) s vs. 81.0 (65.0-107.0 [24.0-178.0]) s, p < 0.001) and additional airway manoeuvres were less frequent (30/166 (18.1%) vs. 91/164 (55.5%), p < 0.001) in the videolaryngoscope group compared with the fibrescope group. The incidence and severity of intubation-related airway complications were not different between the two groups. When performing tracheal intubation in patients with a cervical collar, videolaryngoscopy with a non-channelled Macintosh blade was superior to flexible fibrescopy.

Supraclavicular versus infraclavicular approach for ultrasound-guided right subclavian venous catheterisation: a randomised controlled non-inferiority trial.

Infraclavicular and supraclavicular approaches are used for subclavian venous catheterisation. We hypothesised that the supraclavicular approach is non-inferior to the infraclavicular approach in terms of safety during ultrasound-guided right subclavian venous catheterisation. We randomly allocated 401 neurosurgical patients undergoing ultrasound-guided right subclavian venous catheterisation into supraclavicular (n = 200) and infraclavicular (n = 201) groups. We assessed catheterisation-related complications (primary outcome measure) including catheter misplacement and mechanical complications (arterial puncture, haematoma formation, pneumothorax and haemothorax). We also recorded catheterisation success rates and time required for venous puncture and catheterisation. The number (proportion) of patients with catheterisation-related complications was six (3.0%) in the supraclavicular group and 27 (13.4%) in the infraclavicular group, mean difference (95%CI) -10.4% (-15.7 to -5.1%), p < 0.001, with a significant difference also seen for catheter misplacement. Except for a shorter time (median (IQR [range]) required for venous puncture in the supraclavicular group, being 9 (6-20 [2-138]) vs. 13 (8-20 [3-99]) s, the incidence of mechanical complications and other catheterisation characteristics were similar between the two groups. We recommend the supraclavicular approach for ultrasound-guided right subclavian venous catheterisation.

Metastability of Liquid Water Freezing into Ice VII under Dynamic Compression.

The ubiquitous nature and unusual properties of water have motivated many studies on its metastability under temperature- or pressure-induced phase transformations. Here, nanosecond compression by a high-power laser is used to create the nonequilibrium conditions where liquid water persists well into the stable region of ice VII. Through our experiments, as well as a complementary theoretical-computational analysis based on classical nucleation theory, we report that the metastability limit of liquid water under nearly isentropic compression from ambient conditions is at least 8 GPa, higher than the 7 GPa previously reported for lower loading rates.

Probing the Symmetry Energy with the Spectral Pion Ratio.

Many neutron star properties, such as the proton fraction, reflect the symmetry energy contributions to the equation of state that dominate when neutron and proton densities differ strongly. To constrain these contributions at suprasaturation densities, we measure the spectra of charged pions produced by colliding rare isotope tin (Sn) beams with isotopically enriched Sn targets. Using ratios of the charged pion spectra measured at high transverse momenta, we deduce the slope of the symmetry energy to be 42

Precision hormone therapy: identification of positive responders.

Since the introduction of menopausal hormone therapy (MHT) in the 1940s, randomized clinical trials and observational studies have been performed to determine the benefits and risks of MHT. However, MHT therapeutic impact remains under debate as multiple factors including genetic biomarkers and medical history contribute to inter-individual variations in neurodegenerative diseases. Herein, we review the characteristics of women who participated in clinical studies and methodological approaches for study analyses to assess the critical variables influencing an association between MHT and risk of neurodegenerative diseases. Outcomes of the review indicated that: (1) observational studies assessed outcomes of MHT in symptomatic women whereas MHT clinical trials were conducted in asymptomatic postmenopausal women not treated for menopausal symptoms, (2) in asymptomatic postmenopausal women, late MHT intervention was of no benefit, (3) different MHT treatments and regimens between observational studies and clinical trials may impact outcomes, and (4) observational studies may provide greater predictive validity for long-term neurological health outcomes as MHT was introduced in symptomatic women and administered over a long period of time. Going forward, achieving precision hormone therapy will require a priori identification of symptomatic women appropriate for MHT and the type and dose of MHT appropriate for their genetic profile and health risks.

Incidence of oral anticoagulant interruption among stroke patients with atrial fibrillation and subsequent stroke.

BACKGROUND AND PURPOSE: We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial fibrillation. METHODS: The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K-ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence. RESULTS: Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance [103 episodes (31.3%)] followed by extracranial bleeding [96 episodes (29.2%)]. Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2 DS2 -VASc score were not significantly different between patients with and without recurrent stroke. CONCLUSIONS: A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.

Vaginal compared with intramuscular progestogen for preventing preterm birth in high-risk pregnant women (VICTORIA study): a multicentre, open-label randomised trial and meta-analysis.

OBJECTIVE: To compare the efficacy of two types of progestogen therapy for preventing preterm birth (PTB) and to review the relevant literature. DESIGN: A multicentre, randomised, open-label, equivalence trial and a meta-analysis. SETTING: Tertiary referral hospitals in South Korea. POPULATION: Pregnant women with a history of spontaneous PTB or short cervical length (<25 mm). METHODS: Eligible women were screened and randomised at 16-22 weeks of gestation to receive either 200 mg of vaginal micronised progesterone daily (vaginal group) or an intramuscular injection of 250 mg 17α-hydroxyprogesterone caproate weekly (IM group). Stratified randomisation was carried out according to participating centres and indications for progestogen therapy. This trial was registered at ClinicalTrials.gov (NCT02304237). MAIN OUTCOME MEASURE: Preterm birth (PTB) before 37 weeks of gestation. RESULTS: A total of 266 women were randomly assigned and a total of 247 women (119 and 128 women in the vaginal and IM groups, respectively) were available for the intention-to-treat analysis. Risks of PTB before 37 weeks of gestation did not significantly differ between the two groups (22.7 versus 25.8%, P = 0.571). The difference in PTB risk between the two groups was 3.1% (95% CI -7.6 to 13.8%), which was within the equivalence margin of 15%. The meta-analysis results showed no significant differences in the risk of PTB between the vaginal and IM progestogen treatments. CONCLUSION: Compared with vaginal progesterone, treatment with intramuscular progestin might increase the risk of PTB before 37 weeks of gestation by as much as 13.8%, or reduce the risk by as much as 7.6%, in women with a history of spontaneous PTB or with short cervical length. TWEETABLE ABSTRACT: Vaginal and intramuscular progestogen showed equivalent efficacy for preventing preterm birth before 37 weeks of gestation.

A new aortoiliac calcification scoring system to predict grade C anastomotic leak following rectal cancer surgery.

BACKGROUND: Aortoiliac calcification may be a surrogate marker of decreased visceral perfusion causing anastomotic leak (AL). The aim of this study was to evaluate the predictive role of aortoiliac calcification for AL after rectal cancer surgery. METHODS: We enrolled patients with primary rectal cancer who had restorative resection at our institution between January 2013 and December 2015. An aortoiliac calcification score was calculated as the sum of calcification scores at the infrarenal aorta (0: no, 1: ≤ 3 cm, 2: > 3 cm) and the common iliac arteries (0: no, 1: unilateral, 2: bilateral). AL was classified into three grades: grade A, requiring no intervention; grade B, requiring therapeutic intervention without re-laparotomy; and grade C, requiring re-laparotomy. Clinicopathological characteristics were analyzed to identify risk factors for AL. RESULTS: There were 583 patients. Three-hundred forty-five (59.2%) had an aortoiliac calcification score ≥ 3, and 37 (6.3%) patients experienced AL, in 30 cases (5.1%) grade C AL. Patients with an aortoiliac calcification score ≥ 3 had a higher incidence of grade C AL (6.7% vs. 2.9%, p = 0.045). Multivariate logistic regression analysis revealed that an aortoiliac calcification score ≥ 3 was an independent risk factor for grade C AL (odds ratio = 2.669, 95% confidence interval 1.066-6.686, p = 0.036). CONCLUSIONS: Aortoiliac calcification may be considered a risk factor for grade C AL after rectal cancer surgery.

Search for K_{L}→π

A search for the rare decay K_{L}→π^{0}νν[over ¯] was performed. With the data collected in 2015, corresponding to 2.2×10^{19} protons on target, a single event sensitivity of (1.30±0.01_{stat}±0.14_{syst})×10^{-9} was achieved and no candidate events were observed. We set an upper limit of 3.0×10^{-9} for the branching fraction of K_{L}→π^{0}νν[over ¯] at the 90% confidence level (C.L.), which improved the previous limit by almost an order of magnitude. An upper limit for K_{L}→π^{0}X^{0} was also set as 2.4×10^{-9} at the 90% C.L., where X^{0} is an invisible boson with a mass of 135 MeV/c^{2}.

What influences use of dental services by the Korean disabled people? The role of perceived barriers in dental care system.

OBJECTIVE: To identify the perceived barriers to dental care for disabled people in South Korea using the revised Andersen's model of access to health care. BASIC RESEARCH DESIGN: Cross-sectional analytic interview study. PARTICIPANTS: Korean people with a disability residing in residential facilities, or those at home who attend vocational rehabilitation facilities, special schools, or welfare facilities, were sampled from Seoul and non-Seoul areas in 2016 and were interviewed face-to-face. In total, 456 disabled Koreans, or their primary caregivers participated. RESULTS: Household income, disability duration and perceived barriers in the dental care system were perceived to impact on dental care utilisation, while the need for dental care services did not significantly explain the use of dental care by disabled people in South Korea. Those with low household incomes were less likely to use dental care services, compared to people with moderate and high household incomes. As disability duration increased, disabled people were more likely to use dental services. Those who perceived the barriers to dental care as higher were less likely to use dental services. CONCLUSION: These data suggest that policies are needed to support disabled people with low household incomes. Lowering barriers in the dental care system may encourage people with disabilities to access timely and adequate dental services.

Global transcriptome analysis identifies weight regain-induced activation of adaptive immune responses in white adipose tissue of mice.

OBJECTIVE: Studies have indicated that weight regain following weight loss predisposes obese individuals to metabolic disorders; however, the molecular mechanism of this potential adverse effect of weight regain is not fully understood. Here we investigated global transcriptome changes and the immune response in mouse white adipose tissue caused by weight regain. DESIGN: We established a diet switch protocol to compare the effects of weight regain with those of weight gain without precedent weight loss, weight loss maintenance and chow diet. We conducted a time course analysis of global transcriptome changes in gonadal white adipose tissue (gWAT) during the weight fluctuation. Co-expression network analysis was used to identify functional modules associated with the weigh regain phenotype. Immune cell populations in gWAT were characterized by flow-cytometric immunophenotyping. Metabolic phenotypes were monitored by histological analysis of adipose tissue and liver, and blood-chemistry and body weight/composition analyses. RESULTS: In total, 952 genes were differentially expressed in the gWAT in the weight regain vs the weight gain group. Upregulated genes were associated with immune response and leukocyte activation. Co-expression network analysis showed that genes involved in major histocompatibility complex I and II-mediated antigen presentation and T-cell activation function were upregulated. Consistent with the transcriptome analysis results, flow cytometry demonstrated significant increases in subsets of T cells and proinflammatory M1 macrophages in the gWAT in the weight regain as compared to the weight gain group. In addition, upregulation of adaptive immune responses was associated with high incidence of adipocyte death and upregulation of high mobility group box 1, a well-known component of damage-associated molecular patterns. CONCLUSIONS: Our global transcriptome analysis identified weight regain-induced activation of adaptive immune responses in mouse white adipose tissue. Results suggest that activation of adipocyte death-associated adaptive immunity in adipose tissue may contribute to unfavorable metabolic effects of weight regain following weight loss.

A direct role for hepatitis B virus X protein in inducing mitochondrial membrane permeabilization.

Hepatitis B virus X protein (HBx) acts as a multifunctional protein that regulates intracellular signalling pathways during HBV infection. It has mainly been studied in terms of its interaction with cellular proteins. Here, we show that HBx induces membrane permeabilization independently of the mitochondrial permeability transition pore complex. We generated mitochondrial outer membrane-mimic liposomes to observe the direct effects of HBx on membranes. We found that HBx induced membrane permeabilization, and the region comprising the transmembrane domain and the mitochondrial-targeting sequence was sufficient for this process. Membrane permeabilization was inhibited by nonselective channel blockers or by N-(n-nonyl)deoxynojirimycin (NN-DNJ), a viroporin inhibitor. Moreover, NN-DNJ inhibited HBx-induced mitochondrial depolarization in Huh-7 cells. Based on the results of this study, we can postulate that the HBx protein itself is sufficient to induce mitochondrial membrane permeabilization. Our finding provides important information for a strategy of HBx targeting during HBV treatment.

Delayed viral suppression during antiviral therapy is associated with increased hepatocellular carcinoma rates in HBeAg-positive high viral load chronic hepatitis B.

The treatment option in chronic hepatitis B (CHB) patients with persistent low-level viremia despite entecavir or tenofovir monotherapy is unclear. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B e antigen (HBeAg)-positive high viral load CHB patients, according to the time needed to achieve complete viral suppression. A total of 325 HBeAg-positive CHB patients with high viral load who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were divided into 2 groups with 4 separate criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3 or 4 years of therapy initiation. The outcomes were development of HCC and cirrhosis. The cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03-19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24-9.23; P = .018), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04-3.66; P = .037) or 2 years (HR, 2.44; 95% CI, 1.41-4.22; P = .001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2 years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development.

Entecavir and tenofovir reduce hepatitis B virus-related hepatocellular carcinoma recurrence more effectively than other antivirals.

Nucleos(t)ide analogues (NAs) have been shown to decrease the risk of hepatocellular carcinoma (HCC) recurrence. This study evaluated whether high-potency NAs (entecavir and tenofovir disoproxil fumarate [TDF]) reduce the risk of tumour recurrence more potently than low-potency NAs after curative treatment of hepatitis B virus (HBV)-related HCC. This study included 607 consecutive HBV-related HCC patients treated with surgical resection or radiofrequency ablation. The patients were categorized into three groups according to antiviral treatment: group A (no antiviral; n = 261), group B (low-potency NA; n = 90) and group C (high-potency NA; n = 256). The primary end-point was recurrence-free survival (RFS). During the duration of follow-up, the median RFS was 29.4, 25.1, and 88.2 months in groups A, B and C, respectively (P < .001, log-rank test). The multivariate Cox analysis indicated that group C had a significantly longer RFS than both group A (adjusted hazard ratio [HR] = 0.39, P < .001) and group B (adjusted HR = 0.47, P < .001). When baseline characteristics were balanced using inverse probability weighting, group C still had a significantly longer RFS than group A (adjusted HR = 0.46, P < .001) and group B (adjusted HR = 0.59, P = .007). Group C had significantly lower risk of viral breakthrough than group B (HR = 0.19, P < .001). Viral breakthrough was an independent risk factor for shorter RFS among groups B and C (adjusted HR = 2.03, P = .007, time-dependent Cox analysis). Antiviral agents with high genetic barrier to resistance (entecavir and TDF) reduced the risk of HCC recurrence compared with other antivirals and no antiviral treatment, especially in patients with high baseline viral load.

Comparison of overall survival between antiviral-induced viral suppression and inactive phase chronic hepatitis B patients.

Nucleot(s)ide analogues (NAs) reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. However, the risk of HCC is reportedly higher for NA-treated patients than for patients in the inactive CHB phase. This study aimed to compare the long-term outcomes of CHB patients with NA-induced viral suppression and those of patients with inactive CHB. This retrospective study involved 1118 consecutive CHB patients whose HBV DNA level was continuously <2000 IU/mL during follow-up with/without antiviral agents. The patients were classified into inactive CHB (n = 373) or NA groups (n = 745). The primary endpoint was overall survival. Secondary endpoints included development of HCC and other liver-related events. The median duration of follow-up was 41.0 (interquartile range = 26.5-55.0) months. The difference in overall survival between the NA group vs. the inactive CHB group was not significant (hazard ratio [HR] = 0.78; 95% confidence interval [CI] = 0.33-1.85; P = .57). The NA group showed a significantly higher risk of HCC (HR = 3.44; 95% CI = 1.82-6.52; P < .01), but comparable risk for non-HCC liver-related events (HR = 1.02; 95% CI = 0.66-1.59; P = .93), compared with the inactive CHB group. Among patients with cirrhosis, the NA group showed a significantly lower risk of death (HR = 0.31; 95% CI = 0.097-0.998; P = .05) and non-HCC liver-related events (HR = 0.51; 95% CI = 0.31-0.83; P < .01), but a slightly higher risk of HCC (HR = 2.39; 95% CI = 0.85-6.75; P = .09), compared to the inactive CHB group. The overall survival of untreated patients with inactive CHB and of CHB patients achieving viral suppression with NA was comparable. However, NA treatment of cirrhotic patients was significantly associated with longer overall survival and lower risk of liver-related events.

Tunable quad-band transmission response, based on single-layer metamaterials.

We investigated the electromagnetically induced transparency (EIT)-like effects in planar metamaterials (MMs) at microwave (GHz) frequencies. The specific MMs that were used in this study consist of cut-wire resonator/ring resonator, which achieved the dual EIT-like effects in a single-layer through the bright- and quasi-dark-mode coupling and the lattice mode coupling. In addition, by varying the distance between the two resonators, the quad-band EIT spectral response in the microwave region was obtained, and the group refractive index at the EIT-like resonance of proposed design reached up to 4,000. This study provides the design approach to the multispectral EIT-like effects and might suggest potential applications in a variety of fields, for example, low-loss slow-light device, multiple switching sensor, and other sensing devices.

Longitudinal cortical thinning and cognitive decline in patients with early- versus late-stage subcortical vascular mild cognitive impairment.

BACKGROUND AND PURPOSE: Biomarker changes in cognitively impaired patients with small vessel disease are largely unknown. The rate of amyloid/lacune progression, cortical thinning and cognitive decline were evaluated in subcortical vascular mild cognitive impairment (svMCI) patients. METHODS: Seventy-two svMCI patients were divided into early stage (ES-svMCI, n = 39) and late stage (LS-svMCI, n = 33) according to their Clinical Dementia Rating Sum of Boxes score. Patients were annually followed up with neuropsychological tests and brain magnetic resonance imaging for 3 years, and underwent a second [11 C] Pittsburgh compound B (PiB) positron emission tomography scan within a mean interval of 32.4 months. RESULTS: There was no difference in the rate of increase in PiB uptake or lacune number between the ES-svMCI and LS-svMCI. However, LS-svMCI showed more rapid cortical thinning and cognitive decline than did the ES-svMCI. CONCLUSIONS: We suggest that, whilst the rate of change in pathological burden did not differ between ES-svMCI and LS-svMCI, cortical thinning and cognitive decline progressed more rapidly in the LS-svMCI.

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.