Partial excision of schwannomatosis with fascicular invasion occurring in the ulnar nerve above the elbow: A 1-year follow-up study.

Although not as common as solitary lesions, multiple schwannomas do occur, even in single nerve lesions. We report a rare case of a 47-year-old female patient who presented with multiple schwannomas with inter-fascicular invasion in the ulnar nerve above the cubital tunnel. Preoperative MRI revealed a 10-cm multilobulated tubular mass along the ulnar nerve above the elbow joint. During excision under 4.5° loupe magnification, we separated three ovoid yellow-colored neurogenic tumors of different sizes, but there were still remaining lesions as it was difficult to completely separate lesions from the ulnar nerve due to the risk of iatrogenic nerve ulnar nerve injury. The operative wound was closed. Postoperative biopsy confirmed the diagnosis of the three schwannomas. During the follow-up, the patient recovered without neurological symptom or limitations in range of motion, and there were no neurological abnormalities. At 1year after surgery, small lesions remained in the most proximal part. However, the patient had no clinical symptoms and was satisfied with the surgical results. Although a long-term follow-up is necessary for this patient, we were able to obtain good clinical and radiological results.

Fracture Liaison Service and Its Role in Secondary Fracture Prevention in Malaysia: A Scoping Review

@#Introduction: Fragility fractures, which occur after a lowtrauma injury, increases with advancing age. Such fracture doubles the life-time risk of sustaining another fracture. This risk is highest in the immediate 18 months after the index fracture. However, most patients do not receive the appropriate risk assessment and intervention to reduce this risk. A coordinated model of care termed Fracture Liaison Service (FLS) has been reported to address this treatment gap. Materials and methods: This scoping review aims to explore the potential role and delivery of FLS services in Malaysia. Scientific and non-scientific sources relevant to FLS were identified from electronic bibliographic databases, specialist journals and relevant websites. Findings were categorised into themes and presented narratively. Results: FLS services remain concentrated in the Klang Valley. Even within FLS services, many do not have extensive coverage to risk assess all fracture patients. These services are multidisciplinary in nature where there are links between different departments, such as orthopaedics, osteoporosis expertise, bone densitometry, rehabilitation, falls services and primary care. FLS was able to increase the number of people undergoing fracture risk assessment and treatment. The importance of FLS was highlighted by local experts and stakeholders. Its implementation and delivery are supported by a number of national guidelines. Conclusion: FLS is central to our national efforts to reduce the impending fragility fracture crisis in the coming years. Continued effort is needed to increase coverage within FLS services and across the country. Training, awareness of the problem, research, and policy change will support this endeavour.

The Current and Future Challenges of Hip Fracture Management in Malaysia

@#By 2050, it is predicted that six million hip fractures will occur each year of which the majority will happen in Asia. Malaysia is not spared from this predicted rise and its rate of increase will be one of the highest in this region. Much of this is driven by our unprecedented growth in the number of older people. Characteristics of individuals with hip fractures in Malaysia mirror what has been reported in other countries. They will be older multimorbid people who were already at risk of falls and fractures. Outcomes were poor with at least a quarter do not survive beyond 12 months and in those that do survive have limitation in their mobility and activities of daily living. Reviewing how these fractures are managed and incorporating new models of care, such as orthogeriatric care, could address these poor outcomes. Experts have warned of the devastating impact of hip fracture in Malaysia and that prompt action is urgently required. Despite that, there remains no national agenda to highlight the need to improve musculoskeletal health in the country

New mesh-type phantoms and their dosimetric applications, including emergencies.

Committee 2 of the International Commission on Radiological Protection (ICRP) has constructed mesh-type adult reference computational phantoms by converting the voxel-type ICRP Publication 110 adult reference computational phantoms to a high-quality mesh format, and adding those tissues that were below the image resolution of the voxel phantoms and therefore not included in the Publication 110 phantoms. The new mesh phantoms include all the necessary source and target tissues for effective dose calculations, including the 8-40-µm-thick target layers of the alimentary and respiratory tract organs, thereby obviating the need for supplemental organ-specific stylised models (e.g. respiratory airways, alimentary tract organ walls and stem cell layers, lens of the eye, and skin basal layer). To see the impact of the new mesh-type reference phantoms, dose coefficients for some selected external and internal exposures were calculated and compared with the current reference values in ICRP Publications 116 and 133, which were calculated by employing the Publication 110 phantoms and the supplemental stylised models. The new mesh phantoms were also used to calculate dose coefficients for industrial radiography sources near the body, which can be used to estimate the organ doses of the worker who is accidentally exposed by an industrial radiography source; in these calculations, the mesh phantoms were deformed to reflect the size of the worker, and also to evaluate the effect of posture on dose coefficients.

Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma.

Background: Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic BRD3/4-NUT rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored. Patients and methods: We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence in situ hybridization and using individual fluorescence probes. Results: Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the BRD3/4-NUT oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple BRD3/4-NUT fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the BRD4-NUT rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%-75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells. Conclusion: Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.

Vandetanib in pretreated patients with advanced non-small cell lung cancer-harboring RET rearrangement: a phase II clinical trial.

Background: Chromosomal rearrangements involving RET, which are found in about 1% of non-small cell lung cancer (NSCLC), define a unique molecular subset. We performed this study to examine the efficacy and safety of vandetanib 300 mg daily in this patient population. Patients and methods: This study was a multi-center, open-label, phase II clinical trial. Patients were enrolled if they had metastatic or recurrent NSCLC with a RET rearrangement, which was confirmed by fluorescence in situ hybridization, had progressive disease against platinum-based doublet chemotherapy, and had a performance status of 0-2. The primary endpoint was the objective response rate. Results: A total of 18 patients were enrolled in this study between July 2013 and October 2015. Patients were aged 35-71 years; three had a performance status of 2, and the majority were a heavily pretreated population (≥ two different previous chemotherapy regimens in 72% of the patients). Among the 17 evaluable patients, three had a partial response (objective response rate = 18%) and eight had a stable disease (disease control rate = 65%). Among these patients, the partial response or disease stabilization was durable for more than 6 months in eight patients. Vandetanib also showed a progression-free survival of 4.5 months, and an overall survival of 11.6 months during a median follow-up duration of 14 months. The safety profile was comparable with previous studies of vandetanib. Most vandetanib-related adverse events were mild with prevalent hypertension and rash (in >70% of patients). Grade 3 toxicity included hypertension (n = 3), QT prolongation (2), and elevation of aminotransferases (1), and as a consequence the dose was reduced in four patients. There were no adverse events associated with grade 4 or 5 toxicity. Conclusion: Vandetanib is moderately active in pretreated patients with advanced NSCLC-harboring RET rearrangements.

Centrifugal microfluidic platform for single-cell level cardiomyocyte-based drug profiling and screening.

Drug screening and profiling is an important phase in drug discovery, development, and marketing. However, some profiling tests are not routinely done because of the needed additional technical skills and costly maintenance, which leads to cases of unexpected side effects or adverse drug reactions (ADRs). This study presents the design and operation of a microfluidic chip for single-cell level drug screening and profiling as an alternative platform for this purpose. Centrifugation was utilized to trap isolated single and groups of primary cultured neonatal rat cardiomyocytes in the same chip. In the off-spin operation of the chip, the cells can be observed under a microscope and movies of the beat motion can be recorded. The beat profiles of the cells were generated by image correlation analysis of the recorded video to study the contractile characteristics (beating rate, beating strength, and inter-beat duration). By utilizing this non-invasive tool, long term continuous monitoring, right after trapping, was made possible and cell growth and dynamics were successfully observed in the chip. Media and liquid replacement does not require further centrifugation but instead utilizes capillary flow only. The effect of carbachol (100 µM) and isoproterenol (4 µg mL(-1)) on single cells and groups of cells was demonstrated and the feature for immunostaining (ß-actin) applicability of the chip was revealed. Furthermore, these findings can be helpful for the headway of non-invasive profiling of cardiomyocytes and for future chip design and operation of high-throughput lab-on-a-chip devices.

The association of uterine cervical microbiota with an increased risk for cervical intraepithelial neoplasia in Korea.

Recent studies have suggested potential roles of the microbiome in cervicovaginal diseases. However, there has been no report on the cervical microbiome in cervical intraepithelial neoplasia (CIN). We aimed to identify the cervical microbiota of Korean women and assess the association between the cervical microbiota and CIN, and to determine the combined effect of the microbiota and human papillomavirus (HPV) on the risk of CIN. The cervical microbiota of 70 women with CIN and 50 control women was analysed using pyrosequencing based on the 16S rRNA gene. The associations between specific microbial patterns or abundance of specific microbiota and CIN risk were assessed using multivariate logistic regression, and the relative excess risk due to interaction (RERI) and the synergy index (S) were calculated. The phyla Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, Tenericutes, Fusobacteria and TM7 were predominant in the microbiota and four distinct community types were observed in all women. A high score of the pattern characterized by predominance of Atopobium vaginae, Gardnerella vaginalis and Lactobacillus iners with a minority of Lactobacillus crispatus had a higher CIN risk (OR 5.80, 95% CI 1.73-19.4) and abundance of A. vaginae had a higher CIN risk (OR 6.63, 95% CI 1.61-27.2). The synergistic effect of a high score of this microbial pattern and oncogenic HPV was observed (OR 34.1, 95% CI 4.95-284.5; RERI/S, 15.9/1.93). A predominance of A. vaginae, G. vaginalis and L. iners with a concomitant paucity of L. crispatus in the cervical microbiota was associated with CIN risk, suggesting that bacterial dysbiosis and its combination with oncogenic HPV may be a risk factor for cervical neoplasia.

Modulation of the host response by probiotic Lactobacillus brevis CD2 in experimental gingivitis.

OBJECTIVE: Probiotic Lactobacillus brevisCD2 (CD2) exerts anti-inflammatory properties by preventing nitric oxide synthesis. It is hypothesized that oral application of CD2 can inhibit naturally occurring gingival inflammation. MATERIALS AND METHODS: Thirty-four healthy adults were randomized to receive L. brevisCD2 lozenges or placebo, three times daily for 14 days. The subjects refrained from oral hygiene, the extent of which was determined at various time points. RESULTS: In both groups, bleeding on probing scores increased continuously throughout the study except on day 3. In the placebo group, scores increased significantly from 9.50 at baseline to 14.75 and 14.81 on days 10 and 14, respectively (P < 0.05). No significant change from baseline was observed in the CD2 group. However, scores were consistently higher with placebo, and significant intergroup differences were observed on day 10. Plaque and gingival indices increased from baseline in both treatment groups, but no intergroup differences were observed. Measurements of immune markers in gingival crevicular fluid revealed increased production of nitric oxide in the placebo group (P < 0.05). Prostaglandin E2 production decreased over time in both groups. CONCLUSION: Lactobacillus brevisCD2 may delay gingivitis development in this model by downregulating an inflammatory cascade.

Common Genetic Variant Association with Altered HLA Expression, Synergy with Pyrethroid Exposure, and Risk for Parkinson's Disease: An Observational and Case-Control Study.

BACKGROUND/OBJECTIVES: The common non-coding single nucleotide polymorphism (SNP) rs3129882 in HLA-DRA is associated with risk for idiopathic Parkinson's disease (PD). The location of the SNP in the major histocompatibility complex class II (MHC-II) locus implicates regulation of antigen presentation as a potential mechanism by which immune responses link genetic susceptibility to environmental factors in conferring lifetime risk for PD. METHODS: For immunophenotyping, blood cells from 81 subjects were analyzed by qRT-PCR and flow cytometry. A case-control study was performed on a separate cohort of 962 subjects to determine association of pesticide exposure and the SNP with risk of PD. RESULTS: Homozygosity for G at this SNP was associated with heightened baseline expression and inducibility of MHC class II molecules in B cells and monocytes from peripheral blood of healthy controls and PD patients. In addition, exposure to a commonly used class of insecticide, pyrethroids, synergized with the risk conferred by this SNP (OR = 2.48, p = 0.007), thereby identifying a novel gene-environment interaction that promotes risk for PD via alterations in immune responses. CONCLUSIONS: In sum, these novel findings suggest that the MHC-II locus may increase susceptibility to PD through presentation of pathogenic, immunodominant antigens and/or a shift toward a more pro-inflammatory CD4+ T cell response in response to specific environmental exposures, such as pyrethroid exposure through genetic or epigenetic mechanisms that modulate MHC-II gene expression.

Metabolic syndrome and sex-specific socio-economic disparities in childhood and adulthood: the Korea National Health and Nutrition Examination Surveys.

AIMS: To examine whether adulthood and/or childhood sex-specific socio-economic disparities are associated with metabolic syndrome and its components in a developed non-Western setting. METHODS: Based on the Fourth Korea National Health and Nutrition Examination Surveys, 14 888 people aged ≥ 20 years were analysed to evaluate the effect of adult and childhood socio-economic status on metabolic syndrome. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III guidelines. Logistic regression analyses were conducted to calculate the odds ratios for metabolic syndrome and each component of metabolic syndrome in later life. RESULTS: The age-standardized prevalence of metabolic syndrome was 26.6% for men and 21.3% for women. Compared with the highest level of education, men with the lowest education level were significantly less likely to have metabolic syndrome (odds ratio 0.76, 95% CI 0.60-0.96), whereas the opposite association was found in women (odds ratio 3.29, 95% CI 2.45-4.42). Men who were manual labourers and economically inactive had a lower prevalence of metabolic syndrome compared with those with non-manual jobs (odds ratio 0.82, 95% CI 0.69-0.98 and odds ratio 0.79, 95% CI 0.64-0.99, respectively), but the reverse association was observed in women (odds ratio 1.34, 95% CI 1.04-1.73 and odds ratio 1.40, 95% CI 1.09-1.81, respectively). A significant interaction between combined adulthood and childhood socio-economic status on the presence of metabolic syndrome was observed (P < 0.05). CONCLUSIONS: Our findings suggest that sex-specific socio-economic disparities in childhood and adulthood have differential effects on the prevalence of metabolic syndrome and its individual components in Korea.

Effect of inhalers on the development of haemoptysis in patients with non-cystic fibrosis bronchiectasis.

BACKGROUND: The association of inhaler use with haemoptysis has rarely been reported in patients with non-cystic fibrosis (CF) bronchiectasis. OBJECTIVE: To elucidate the effect of inhaler use on the development of haemoptysis in patients with non-CF bronchiectasis. METHODS: In a case-crossover study of 192 non-CF bronchiectasis patients with a history of haemoptysis and inhaler use, the risk of haemoptysis associated with the use of inhalers was elucidated. Two inhaled corticosteroids/long-acting ß2-agonists (ICS/LABA), one long-acting muscarinic antagonist and one short-acting ß2-agonist (SABA) were evaluated. The case and control periods were defined respectively as 030 and 180210 days before haemoptysis. RESULTS: The risk of haemoptysis during the case period was 3.51 times higher than during the control period with any use of inhalers (95%CI 1.966.28). The results of clinically significant haemoptysis showed good agreement with those of total events. These associations were consistent with the sensitivity analyses. In the sub-analysis according to inhaler type, ICS/LABA and SABA were significantly associated with an increased risk of haemoptysis (aOR 2.62, 95%CI 1.255.45; aOR 2.51, 95%CI 2.235.15). CONCLUSIONS: In patients with non-CF bronchiectasis, the use of inhalers, especially including 2-agonist, was associated with an increased risk of haemoptysis.

Osteoprotegerin, inflammation and dyslipidemia are associated with abdominal aortic calcification in non-diabetic patients on peritoneal dialysis.

BACKGROUND AND AIMS: Abdominal aortic calcification (AC) has been reported to be associated with cardiovascular disease (CVD) in hemodialysis patients but is rarely discussed in peritoneal dialysis (PD) patients. We examined the independent predictors and predictive power for survival of AC in prevalent PD patients. METHODS AND RESULTS: AC was detected by computed tomography (CT) and represented as the percentage of the total aortic cross-section area affected by AC (%AC). The predictors of %AC ≥ 15 were examined by multiple logistic regression analysis. Cox proportional hazard analysis was used to determine the hazard ratios associated with high %AC. A total of 183 PD patients were recruited to receive CT scans and divided into group 1 (%AC < 15, n = 97), group 2 (%AC ≥ 15, n = 41), and group 3 (diabetic patients, n = 45). Group 1 patients had lower osteoprotegerin (OPG) levels than group 2 patients (798 ± 378 vs. 1308 ± 1350 pg/mL, p < 0.05). The independent predictors for %AC ≥ 15 included the atherogenic index, OPG, and C-reactive protein (CRP). The age-adjusted hazard ratios associated with %AC ≥ 15 were 3.46 (p = 0.043) for mortality and 1.90 (p = 0.007) for hospitalization. CONCLUSIONS: %AC can predict mortality and morbidity in non-diabetic PD patients, and 15% is a good cut-off value for such predictions. There are complex associations among mineral metabolism, inflammation, and dyslipidemia in the pathogenesis of AC.

Antimicrobial efficacy of a human ß-defensin-3 peptide using an Enterococcus faecalis dentine infection model.

AIM: To assess the antibacterial efficacy of a human ß-defensin-3 (HBD3) peptide against Enterococcus faecalis biofilms. METHODOLOGY: Standardized human dentine blocks were infected with E. faecalis ATCC 29212 for 3 weeks. Aqueous calcium hydroxide paste (n = 12, CH), a 2% chlorhexidine gel (n = 12, CHX), an HBD3 peptide gel (n = 12) and saline (n = 12) were tested as experimental groups. A mismatched peptide gel group (n = 12, MP) and sterilized but noninoculated block group (n = 12) were included as controls. After 1 week of medication, the dentinal samples at the depth of 200 and 400 µm were collected from medicated canal lumens. Bacterial growth was assessed by spectrophotometric analysis of optical density (OD) after 72 h of incubation. Statistical analysis was performed with repeated-measures anova and Tukey's post hoc test. RESULTS: The HBD3 group was associated with significantly lower OD values (P < 0.05) than the CH or CHX groups at both depths. The CH group did not differ significantly from MP or Saline group at either depth (P > 0.05). There was no significant difference (P > 0.05) in the OD values of the inner (200 µm) and outer (400 µm) dentinal samples for any group. CONCLUSIONS: The HBD3 peptide inhibited the growth of E. faecalis biofilms in infected dentine blocks.

Silencing of Twist1 sensitizes NSCLC cells to cisplatin via AMPK-activated mTOR inhibition.

Twist1 is highly expressed in primary and metastatic non-small cell lung cancer (NSCLC), and thus acts as a critical target for lung cancer chemotherapy. In the current study, we investigated the underlying mechanism initiated by silencing of Twist1 that sensitizes NSCLC cells to cisplatin. Silencing of Twist1 triggered ATP depletion, leading to AMP-activated protein kinase (AMPK)-activated mammalian target of rapamycin (mTOR) inhibition in NSCLC cells. AMPK-induced mTOR inhibition, in turn, resulted in downregulation of ribosome protein S6 kinase 1 (S6K1) activity. Downregulation of mTOR/S6K1 reduced Mcl-1 protein expression, consequently promoting sensitization to cisplatin. Overexpression of Mcl-1 reduced PARP cleavage induced by cisplatin and Twist1 siRNA, suggesting that this sensitization is controlled through Mcl-1 expression. Interestingly, cells treated with Twist1 siRNA displayed upregulation of p21(Waf1/CIP1), and suppression of p21(Waf1/CIP1) with specific siRNA further enhanced the cell death response to cisplatin/Twist1 siRNA. In conclusion, silencing of Twist1 sensitizes lung cancer cells to cisplatin via stimulating AMPK-induced mTOR inhibition, leading to a reduction in Mcl-1 protein. To our knowledge, this is the first report to provide a rationale for the implication of cross-linking between Twist1 and mTOR signaling in resistance of NSCLC to anticancer drugs.

A biometric study of C-shaped root canal systems in mandibular second molars using cone-beam computed tomography.

AIM: To investigate the configuration of C-shaped canals in mandibular second molars, canal wall thickness and the orientation of the thinnest area at 1-mm intervals from the canal orifice to the apex by using cone-beam computed tomographic (CBCT) images. METHODOLOGY: Three-dimensional CBCT images of 92 Korean mandibular second molars having C-shaped root canals were analysed to determine their configuration using a modification of Melton's classification, as well as the thinnest walls and their location. Associations between configuration type and distance from the canal orifice to the apex, as well as associations between the directional orientation of the thinnest root wall and distance from the canal orifice to the apex, were assessed by Fisher's exact test. Because serial measurements of minimum wall thicknesses were correlated with individual teeth, a mixed-effects analysis was applied. RESULTS: The most common configuration types were Melton's type I in the coronal region and Melton's type III in the apical region. Mean thicknesses of the thinnest root canal walls were 1.39 ± 0.38, 0.85 ± 0.25 and 0.77 ± 0.20 mm in the coronal, middle and apical regions, respectively. The thicker the root canal walls at the orifice region, the greater the decrease in thickness towards the apical region (P < 0.05), with the linguo-central root area being the thinnest. The pattern of decreasing thickness from the orifice to the apex formed a nonlinear cubic curve. CONCLUSIONS: The most prevalent configuration types were Melton's type I (coronal region) and type III (apical region). The linguo-central root area was the thinnest in C-shaped root canals of Korean mandibular second molars. These anatomical variations should be considered during surgical or nonsurgical endodontic procedures.

A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation.

OBJECTIVES: In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. METHODS: A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. RESULTS: Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes with no changes in other ionic currents. CRP did not affect the expressions of type I alpha 1 (COL1A1), type III alpha 1 (COL3A1) and type 1 alpha 2 (COL1A2) procollagens in atrial fibroblasts. CONCLUSION: A CRP gene promoter triallelic polymorphism was associated with CRP gene promoter activity, determined the plasma level of CRP, and predicted the risk of AF. The mechanism of this may be via augmention of calcium influx by CRP in atrial myocytes, but not because of atrial fibrosis.

Carotid intima-media thickness in Chinese Type 2 diabetic subjects with or without microalbuminuria.

BACKGROUND: To examine the association of microalbuminuria (MAU) with the carotid intima-media thickness (CIMT) in Chinese Type 2 diabetic subjects. MATERIALS AND METHODS: Two hundred and thirty-nine patients (64±13 yr, 154 males) were divided into 2 groups: one with MAU (no.=119) or one without (no.=120). We recorded clinical and biochemical data as well as CIMT and ankle-brachial index (ABI). RESULTS: The patients with MAU had had diabetes mellitus (DM) longer, had higher blood pressure (BP). They also had lower estimated glomerular filtration rate (eGFR) and higher levels of circulating glucose, glycated hemoglobin, high sensitivity C-reactive protein than those without. Lower mean ABI was found in those with MAU, however, they did not have higher mean CIMT (0.72±0.15 vs 0.71±0.16 mm, p=0.525). In patients without MAU, CIMT correlated with age, DM duration, systolic BP, eGFR, albumin- to-creatinine ratio, and ABI. However, in those with MAU, CIMT correlated only with age and eGFR. Multivariate regression analysis revealed that mean CIMT correlated only with age for patients without MAU, but correlated with age and body mass index for those with MAU. Dividing the patients into 5 age groups, we found that the older the patient, the higher the mean CIMT with no group differences between those with and without MAU in both genders. However, patients with eGFR below 60 ml/min/1.73 m(2) had higher mean CIMT than those above (0.75±0.16 vs 0.69±0.14 mm, p=0.005). CONCLUSIONS: Type 2 diabetic patients with MAU were not associated with higher CIMT. Conversely, those with deterioration of renal function were more likely associated.

Differential association of proinflammatory cytokines with left ventricular diastolic dysfunction in subjects with and without continuous ambulatory peritoneal dialysis.

BACKGROUND AND AIMS: The association between inflammation and left ventricular (LV) diastolic dysfunction in continuous ambulatory peritoneal dialysis (CAPD) and non-CAPD patients is not established. The objective of this study was to test the above association and whether inflammation interacts with CAPD to increase LV diastolic dysfunction risks. METHODS AND RESULTS: 120 subjects with normal creatinine levels and 101 CAPD patients were recruited. Echocardiographic parameters were assessed in all patients. The participants were classified as having LV diastolic dysfunction by echocardiographic findings including mitral inflow E/A ratio < 1, deceleration time > 220 cm/s, or decreased peak annular early diastolic velocity in tissue Doppler imaging. Blood was sampled at the baseline for measurement of inflammation markers, including tissue necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Subjects with LV diastolic dysfunction had higher proinflammation cytokines levels in both groups. Inflamed markers correlated significantly with echocardiography parameters for LV diastolic dysfunction in patients receiving CAPD. In a multivariate regression analysis adjusting for all the factors associated with LV diastolic dysfunction, inflammation is still significantly associated with left ventricular diastolic dysfunction (TNF-alpha, OR: 2.6, 95% CI: 2.0-3.35, p < 0.001; IL-6, OR: 1.26, 95% CI: 1.25-1.26, p = 0.01). In addition, the interaction of CAPD and inflammation significantly contributed to the development of LV diastolic dysfunction (CAPD∗ TNF-α: OR: 1.45, 95% CI: 1.13-1.79, P = 0.004). CONCLUSION: We found inflammation plays a vital role for LV diastolic dysfunction especially in CAPD patients. A synergistic effect between CAPD and inflammation, especially TNF-α, would further aggravate LV diastolic dysfunction.