Impaired arterial responsiveness in untreated gout patients compared with healthy non-gout controls: association with serum urate and C-reactive protein

To determine whether arterial responsiveness is impaired among patients with gout, and whether arterial responsiveness inversely correlates with serum urate and inflammatory measures. This is a cross-sectional study of untreated gout subjects (n?=?34) and non-gout healthy controls (n?=?64). High-resolution dynamic ultrasound-measured flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) assessed endothelium-dependent and endothelium-independent arterial responsiveness respectively. Serum urate (sUA) and high-sensitivity C-reactive protein (hsCRP) were measured in the gout group, and correlated with FMD and NMD responses. Both FMD (2.20?±?0.53 vs 3.56?±?0.31, p?=?0.021) and NMD (16.69?±?1.54 vs 24.51?±?0.90, p?=?0.00002) were impaired in the gout versus control group. Stratification for individual comorbidities suggested that no single risk factor accounted for impaired FMD/NMD in the gout subjects. However, the degree of association between gout and FMD, but not NMD impairment, was dampened after multivariable adjustment (FMD unadjusted beta?=???1.36 (SE 0.58), p?=?0.02; adjusted beta?=???1.16 (SE 0.78), p?=?0.14 and NMD unadjusted beta?=???7.68 (SE 1.78), p?<?0.0001; adjusted beta?=???5.33 (SE 2.46), p?=?0.03). Within the gout group, there was an inverse correlation between FMD and sUA (R?=???0.5, p?=?0.003), and between FMD and hsCRP (R?=???0.42, p?=?0.017), but not between NMD and sUA or hsCRP. Compared with healthy controls, subjects with gout have reduced arterial function. Individual comorbidities are insufficient to account for differences between gout and control groups, but multiple comorbidities may collectively contribute to impairment in endothelium-dependent arterial responsiveness. Endothelial impairment is also related to sUA and hsCRP, markers of gout severity and inflammation respectively. Studies to determine whether gout therapy may improve arterial responsiveness are warranted.     

Intermittent and constant pain and physical function or performance in men and women with knee osteoarthritis: data from the osteoarthritis initiative

Severe constant and intermittent knee pain are associated with “unacceptable” symptoms in older adults with osteoarthritis (OA) [22]. We hypothesized that constant and intermittent pain would be independently related to physical function, with intermittent knee pain being a better predictor of future declines in physical function in early symptomatic knee OA. This study included men (n?=?189) and women (n?=?133) with radiographic, unilateral knee OA, observed using data from the Osteoarthritis Initiative (OAI). Pain types were measured using the Intermittent and Constant Osteoarthritis Pain (ICOAP) scale. Physical function was measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC-PF) and Knee Injury and Osteoarthritis Outcome Score (KOOS-FSR) and physical performance tests. High baseline intermittent (B?=?0.277; p?=?0.001) and constant (B?=?0.252; p?=?0.001) knee pain were related to poor WOMAC-PF. Increased constant (B?=?0.484; p?=?0.001) and intermittent (B?=?0.104; p?=?0.040) pain were related to 2-year decreased WOMAC-PF. High baseline intermittent knee pain predicted poor KOOS-FSR at year 2 (B?=??0.357; p?=?0.016). Increased constant pain was related to decreased chair stand test performance over 2 years in women (B?=?0.077; p?=?0.001). High baseline intermittent pain was related to poor performance on repeated chair stands (B?=?0.035; p?=?0.021), while baseline constant pain was related to poor 400-m walk performance in women (B?=?0.636; p?=?0.047). Intermittent and constant knee pain were independent factors in self-perceived physical function and were important predictors of future limitations in physical function. Identifying intermittent and constant pain in early symptomatic OA may allow patients to adopt strategies to prevent worsening pain and future declines in physical function.     

Expression of α-Defensins,CD20+ B-lymphocytes,and Intraepithelial CD3+ T-lymphocytes in the Intestinal Mucosa of Patients with Liver Cirrhosis: Emerging Mediators of Intestinal Barrier Function

Aim

The present study investigates the role of innate and adaptive immune system of intestinal mucosal barrier function in cirrhosis.

Methods

Forty patients with decompensated (n?=?40, group A), 27 with compensated cirrhosis (n?=?27, group B), and 27 controls (n?=?27, group C) were subjected to duodenal biopsy. Expression of α-defensins 5 and 6 at the intestinal crypts was evaluated by immunohistochemistry and immunofluorescence. Serum endotoxin, intestinal T-intraepithelial, and lamina propria B-lymphocytes were quantified.

Results

Cirrhotic patients presented higher endotoxin concentrations (p?<?0.0001) and diminished HD5 and HD6 expression compared to healthy controls (p?=?0.000287, p?=?0.000314, respectively). The diminished HD5 and HD6 expressions were also apparent among the decompensated patients compared to compensated group (p?=?0.025, p?=?0.041, respectively). HD5 and HD6 expressions were correlated with endotoxin levels (r?=?-0.790, p?<?0.0001, r?=???0.777, p?<?0.0001, respectively). Although intraepithelial T-lymphocytes were decreased in group A compared to group C (p?=?0.002), no notable alterations between groups B and C were observed. The B-lymphocytic infiltrate did not differ among the investigated groups.

Conclusions

These data demonstrate that decreased expression of antimicrobial peptides may be considered as a potential pathophysiological mechanism of intestinal barrier dysfunction in liver cirrhosis, while remodeling of gut-associated lymphoid tissue as an acquired immune response to bio-pathogens remains an open field to illuminate.

     

Patient characteristics and outcomes in adolescents and young adults with classical Philadelphia chromosome-negative myeloproliferative neoplasms

Little is known about the outcomes of Philadelphia-negative myeloproliferative neoplasms (MPNs) in adolescents and young adults (AYA). We reviewed all patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) treated at our institution from 1988 to 2016 who were aged 16 to 39 years (AYA) and described their outcomes in comparison to older MPN population. Of 2206 patients, 185 (8.3%) were identified as AYA: 105 (57%) ET, 43 (23%) PV, and 37 (20%) MF. The median age was 33 years [range, 16–39], and median follow-up time 3 years [range, 0.04–25]. JAK2 allele burdens were significantly lower among AYA JAK2V617F-mutated patients in both PV (p?=?0.001) and MF (p?=?0.005). Seven percent of MPN AYA patients were diagnosed with a thrombotic event at, or prior to, diagnosis. Over the short median follow-up, 4 thrombotic (PV?=?1, MF?=?3) and 3 leukemia (ET?=?2, MF?=?1) events occurred. In multivariate analysis, AYA did not predict for thrombotic or transformational events across three cohorts. In the MF cohort, there was a reduced frequency of negative prognostic variables of anemia (p?=?0.011) and leukocytosis (p?=?0.048) in AYA when compared with non-AYA. Overall survival was significantly superior in the AYA cohorts in all three MPN groups, namely MF (p?<?0.001), PV (p?<?0.001), and ET (p?=?0.002). Our findings suggest that MPN AYA patients exhibit an indolent clinical phenotype characterized by favorable survival outcomes.     

Association of plasma somatostatin with disease severity and progression in patients with autosomal dominant polycystic kidney disease

Background

Somatostatin (SST) inhibits intracellular cyclic adenosine monophosphate (cAMP) production and thus may modify cyst formation in autosomal dominant polycystic kidney disease (ADPKD). We investigated whether endogenous plasma SST concentration is associated with disease severity and progression in patients with ADPKD, and whether plasma SST concentrations change during treatment with a vasopressin V2 receptor antagonist or SST analogue.

Methods

In this observational study, fasting concentrations of SST were measured in 127 ADPKD patients (diagnosed upon the revised Ravine criteria) by ELISA. cAMP was measured in 24?h urine by Radio Immuno Assay. Kidney function was measured (mGFR) as ¹²⁵I-iothalamate clearance, and total kidney volume was measured by MRI volumetry and adjusted for height (htTKV). Disease progression was expressed as annual change in mGFR and htTKV. Additionally, baseline versus follow-up SST concentrations were compared in ADPKD patients during vasopressin V2 receptor antagonist (tolvaptan) (n?=?27) or SST analogue (lanreotide) treatment (n?=?25).

Results

In 127 ADPKD patients, 41?±?11?years, 44% female, eGFR 73?±?32?ml/min/1.73m², mGFR 75?±?32?ml/min/1.73m² and htTKV 826 (521–1297) ml/m, SST concentration was 48.5 (34.3–77.8) pg/ml. At baseline, SST was associated with urinary cAMP, mGFR and htTKV (p?=?0.02, p?=?0.004 and p?=?0.02, respectively), but these associations lost significance after adjustment for age and sex or protein intake (p?=?0.09, p?=?0.06 and p?=?0.15 respectively). Baseline SST was not associated with annual change in mGFR, or htTKV during follow-up (st. β?=???0.02, p?=?0.87 and st. β?=???0.07, p?=?0.54 respectively). During treatment with tolvaptan SST levels remained stable 38.2 (23.8–70.7) pg/mL vs. 39.8 (31.2–58.5) pg/mL, p?=?0.85), whereas SST levels decreased significantly during treatment with lanreotide (42.5 (33.2–55.0) pg/ml vs. 29.3 (24.8–37.6), p?=?0.008).

Conclusions

Fasting plasma SST concentration is not associated with disease severity or progression in patients with ADPKD. Treatment with lanreotide caused a decrease in SST concentration. These data suggest that plasma SST cannot be used as a biomarker to assess prognosis in ADPKD, but leave the possibility open that change in SST concentration during lanreotide treatment may reflect therapy efficacy.

     

Platelet hyperaggregability in patients with atrial fibrillation

Objective

Atrial fibrillation (AF) is a condition where platelet hyperaggregability is commonly present. We examined potential physiological bases for platelet hyperaggregability in a cohort of patients with acute and chronic AF. In particular, we sought to identify the impact of inflammation [myeloperoxidase (MPO) and C-reactive protein (CRP)] and impaired nitric oxide (NO) signaling.

Methods

Clinical and biochemical determinants of adenosine diphosphate (ADP)-induced platelet aggregation were sought in patients (n?=?106) hospitalized with AF via univariate and multivariate analysis.

Results

Hyper-responsiveness of platelets to ADP was directly (r?=?0.254, p?<?0.01) correlated with plasma concentrations of thrombospondin-1 (TSP-1), a matricellular protein that impairs NO responses and contributes to development of oxidative stress. In turn, plasma TSP-1 concentrations were directly correlated with MPO concentrations (r?=?0.221, p?<?0.05), while MPO concentrations correlated with those of asymmetric dimethylarginine (ADMA, r?=?0.220, p?<?0.05), and its structural isomer symmetric dimethylarginine (SDMA, r?=?0.192, p?=?0.05). Multivariate analysis identified TSP-1 (β?=?0.276, p?<?0.05) concentrations, as well as female sex (β?=?0.199, p?<?0.05), as direct correlates of platelet aggregability, and SDMA concentrations (β?=???0.292, p?<?0.05) as an inverse correlate.

Conclusion

We conclude that platelet hyperaggregability, where present in the context of AF, may be engendered by impaired availability of NO, as well as via MPO-related inflammatory activation.

     

Atherogenic index of plasma: a useful marker for subclinical atherosclerosis in ankylosing spondylitis

Ankylosing spondylitis (AS) is associated with an increased risk of atherosclerotic cardiovascular disease (ACD). The atherogenic index of plasma (AIP), which is the logarithmic transformation of the plasma triglyceride (TG) level to the high-density lipoprotein level (HDL) ratio, has been suggested to be a novel marker in the identification of atherosclerosis risk. Therefore, this study aims to determine if the AIP can act as an accurate marker for the detection of subclinical atherosclerosis. Fifty-two male patients with AS and 52 age-, gender-, and body mass index (BMI)-matched healthy control subjects were included in the study. For each patient, AIP and total cholesterol (TC)/HDL values were calculated and carotid artery intima-media thickness (cIMT) was measured. The mean (SD) cIMT and median (range) AIP values for AS patients were higher than that of the healthy control subjects (0.60?±?0.18 vs. 0.51?±?0.10, p?=?0.003 and 0.23 [??0.32 to 0.85] vs. 0.09 [??0.53 to 0.49], p?=?0.007, respectively). A positive correlation was found between the patients’ cIMT and AIP values (r?=?0.307, p?=?0.002) and TC/HDL values (r?=?0.241, p?=?0.014). Regression analysis revealed an independent association between the subclinical atherosclerosis and AIP (beta [β]?=?0.309, p?=?0.002). There were no independent correlations between subclinical atherosclerosis and TC (β?=?0.245, p?=?0.065), TG (β?=?0.185, p?=?0.515), HDL (β?=?0.198, p?=?0.231), TC/HDL (β?=?0.032, p?=?0.862), and low-density lipoprotein (LDL) (β?=?0.151, p?=?0.246). A strong and independent correlation exists between AIP and cIMT values. Therefore, the AIP could serve as a better marker than the TC/HDL ratio for the detection of subclinical atherosclerosis in AS patients.     

Serum BAFF in Indian patients with IIM: a retrospective study reveals novel clinico-phenotypic associations in children and adults

We studied the serum levels of B cell survival factors BAFF and APRIL in patients with idiopathic inflammatory myositis (IIM) and their relation with clinical and autoantibodies. Seventy-five patients (51 females and 24 males) with IIM (Bohan and Peter’s criteria 1975) and 25 healthy adults were analyzed for BAFF, APRIL and IL-17 by ELISA, and myositis-specific and associated antibodies (MSA and MAA) using line immunoblot assay. Of the 75 patients, 59 were adults, 42 had Dermatomyositis (DM), and 17 had Polymyositis. Median disease duration was 5 (3–12) months. BAFF levels were higher in IIM than healthy controls [p?=?0.001], and in children with jDM than adults [p?=?0.026]. BAFF levels were higher in adults with arthritis [p?=?0.018], weight loss [p?=?0.007], and PAH [p?=?0.004]. Among the various MSAs, lowest levels were seen in those with anti-SRP [p?=?0.043]. Median follow-up duration was 145 patient years. Twelve patients relapsed, while nine were in drug-free remission. BAFF were similar between these groups. Serum APRIL levels were elevated in limited number of patients with myositis, and the levels did not differ amongst the clinico-serologic phenotypes. IL-17 levels were higher in individuals positive for anti-SRP [p?=?0.028]. Serum BAFF levels are elevated in IIM, more so in children. BAFF levels may be useful as biomarker for PAH and arthritis. Anti-SRP positivity is associated with elevated IL-17 levels suggesting role in pathogenesis.     

The role of gender in the active attitude toward treatment and health among older patients in primary health care—self-assessed health status and sociodemographic factors as moderators

Background

Active attitude toward treatment and health (ATH) leads to improved cooperation and better health outcomes in patients. Supporting it in the population of older adults is a growing need in primary care. Recognising the role of gender, health and other sociodemographic factors can help to distinguish patients who need the most assistance in activation from general practitioners (GPs). The objective of the study was to investigate gender differences in ATH as well as the moderating role of self-assessed health (SAH) and selected sociodemographic factors (age, education, financial status, marital status).

Methods

A cross-sectional, multicentre study among 4936 primary care older patients (aged 50+) was conducted. The PRACTA-Attitude toward Treatment and Health questionnaire (PRACTA-ATH) was used to measure the cognitive, emotional (positive and negative affect), and motivational dimensions of ATH. Patients were approached before and after their visits in the primary health-care facilities randomly selected in Central Poland.

Results

Generalised linear models (GENLIN) revealed the main effects of gender, SAH, and sociodemographic characteristics, such as financial status, marital status and education. Interaction effects of gender and age (Wald’s χ²?=?24.767, p?<?0.001 for ATH Global), as well as gender and SAH (Wald’s χ²?=?16.712, p?<?0.002 for ATH Global) on ATH were found. The most assistance in regard to ATH was required by men aged 50–74 and men declaring good self-assessed health. Generally, women declared a more active attitude than men, showing more knowledge (M?=?5.40, SD?=?0.07 and M?=?5.21, SD?=?0.07, for women and men, respectively, p?=?0.046), positive emotion (M?=?5.55, SD?=?0.06 and M?=?5.33, SD =0.06, for women and men, respectively, p?=?0.015) and motivation to be involved in their health issues (M?=?5.71, SD?=?0.07 and M?=?5.39, SD?=?0.07, for women and men, respectively, p?=?0.001). The level of negative emotions related to health was not significantly different between genders (p?=?0.971).

Conclusions

The need to create health promoting programmes taking account of particular gender differences in older adults emerges. In regard to clinical practice, building a sense of efficacy and individual responsibility for health, providing information about the means of health promotion and prevention, and recognising health-related cognitions, is recommended especially for men who feel well and are less advanced in age (50–74).

     

Association between arterial stiffness,disease activity and functional impairment in ankylosing spondylitis patients: a cross-sectional study

Cardiovascular risk is an important factor for increased morbidity and mortality in patients with ankylosing spondylitis. The aim of this study is to assess arterial stiffness in relation to the disease activity and functional limitation in patients with ankylosing spondylitis. Twenty-four patients (mean age 45.8?±?11.7 years) suffering of ankylosing spondylitis (disease duration 11.1?±?5.1 years) and 24 gender and age-matched healthy controls were included in the study. Clinical, biological, and functional status of ankylosing spondylitis patients was recorded. Arterial stiffness was assessed by measuring pulse wave velocity (PWV) and pulse wave analysis (PWA) was performed using applanation tonometry. We found significant differences between ankylosing spondylitis patients and healthy controls in regard to PWV (p?=?0.047), aortic augmentation pressure—AP (p?=?0.028), augmentation index—AIx (p?=?0.038) and aortic augmentation index adjusted for heart rate—AIx75 (p?=?0.011). PWV and AIx75 were significantly associated with the disease functioning score—BASFI (p?=?0.012, r?=?0.504; p?=?0.041, r?=?0.421). Aortic AP and augmentation indexes (AIx and AIx75) were all associated to ASDAS score (p?=?0.028, r?=?0.448; p?=?0.005, r?=?0.549; p?=?0.025, r?=?0.455). Our study showed that ankylosing spondylitis patients have a higher arterial stiffness than the age-matched controls, leading to an increased cardiovascular risk. We found that arterial stiffness is positively associated with disease activity and functional impairment. Chronic spondiloarthropaties should be screened for arterial stiffness, even in the absence of traditional cardiovascular risk factors, in order to benefit from primary prevention measures.     

Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis

Systemic sclerosis (SSc) is an autoimmune disease which may lead to malnutrition. Previous studies have defined it with different criteria. No thorough evaluations of sarcopenia in SSc are available. The aim of the present study was to assess the prevalence and the potential association of malnutrition and sarcopenia in a large cohort of SSc cases. A total of 141 SSc consecutive outpatients were enrolled. Body composition was analyzed by densitometry. Malnutrition was defined according to recently published ESPEN criteria, whereas sarcopenia was diagnosed in patients with reduced skeletal muscle index. Malnutrition was diagnosed in 9.2% of patients (95% CI, 4.4–14.0%). Malnourished patients had worse gastrointestinal symptoms according to UCLA SCTC GIT 2.0 questionnaire (p?=?0.007), lower physical activity (p?=?0.028), longer disease duration (p?=?0.019), worse predicted DLCO/VA and FVC (p?=?0.009, respectively), worse disease severity according to Medsger severity score (p?<?0.001), lower hemoglobin (p?=?0.023), and fat-free mass (p?<?0.001) and were more often sarcopenic (p?<?0.001). In multivariate analysis, only FVC (p?=?0.006) and disease severity (p?=?0.003), in particular for the lungs (p?=?0.013), were confirmed to be worse in malnourished patients. Sarcopenia was diagnosed in 29\140 patients (20.7%; 95% CI, 14.0–27.4%); 11\29 were also malnourished. In multivariate analysis, sarcopenic patients had longer disease duration (p?=?0.049), worse DLCO/VA (p?=?0.002), and lung (p?=?0.006) and skin (p?=?0.014) involvement. In SSc, malnutrition defined with ESPEN criteria was found to be lower than previously reported. Sarcopenia was found to be somewhat common. Lung involvement was significantly associated with nutritional status and may not be explained only by muscle weakness.     

Temporal trajectory of quality of life and its predictors in recipients of hematopoietic stem cell transplantation

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p?<?0.001), followed by recovery over 6 months. The conditioning regimen for SCT showed no correlation with HRQOL at T2 (p?=?0.283) or T3 (p?=?0.799), with no significant difference in HRQOL between allogeneic and autologous SCT recipients at T2 (p?=?0.829) or T3 (p?=?0.824). Depression (p?=?0.042), pain (p?=?0.023), and appetite loss (p?=?0.004) negatively influenced HRQOL at T1, whereas only pain (p?=?0.048) remained an important factor at T2. Six months after SCT, the two most frequent symptoms, fatigue and financial problems, became major factors (p?=?0.004 and p?=?0.005, respectively). Depression began to play an important role in HRQOL again at T3 (p?=?0.040). These findings demonstrate that SCT recipients need both psychological and medical support to achieve a better HRQOL after SCT.     

CPAP therapy induces favorable short-term changes in epicardial fat thickness and vascular and metabolic markers in apparently healthy subjects with obstructive sleep apnea-hypopnea syndrome (OSAHS)

Background

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is an independent risk factor for hypertension, coronary artery disease, and diabetes mellitus. Epicardial fat has been recently recognized as a new risk factor and active participant on cardiometabolic risk. The aim of this study was to assess an independent relationship between sleep apnea severity, metabolic and vascular markers, and epicardial fat, at baseline and after 3 months of continuous positive airway pressure (CPAP) therapy.

Materials and method

Our study group consisted of 48 patients with suspected OSAHS and no prior history of cardiovascular disease or diabetes mellitus. All patients underwent full overnight polysomnography. Thickness of epicardial and visceral adipose tissue, brachial artery flow-mediated dilation (FMD), carotid intima media thickness (cIMT), pulse wave velocity (PWV), plasma C-reactive protein (CRP) levels, fasting glucose levels, HbA1c, homeostatic model assessment of insulin resistance index (HOMA), and lipid profile were measured at baseline and after 3 months of CPAP use in patients with moderate to severe OSAHS.

Results

In OSAHS patients (Apnea-hypopnea index (AHI) ≥15/h, N?=?28), epicardial fat correlated with fasting glucose (rho?=?0.406, p?=?0.04) and HOMA (rho?=?0.525, p?=?0.049) but was not associated with visceral fat (rho?=?0.126, p?=?0.595). Epicardial adipose tissue (EAT) (p?=?0.022) increased across AHI severity along with PWV (p?=?0.045) and carotid intima media thickness (IMT) (p?=?0.034) while FMD (p?=?0.017) decreased. Therapy with CPAP reduced both epicardial (p?<?0.001) and visceral fat (p?=?0.001). Alterations in epicardial fat across the follow-up were associated with changes in PWV (p?=?0.026) and HOMA (p?=?0.037) independently of major confounders.

Conclusions

Epicardial fat thickness was associated with OSA severity and may be an additional marker of cardiovascular risk as well as of future diabetes in these patients. CPAP therapy reduced epicardial fat, suggesting its potentially beneficial role in reducing cardiometabolic risk in OSA patients.

     

Association between susceptibility to rheumatoid arthritis and <Emphasis Type="Italic">PADI4</Emphasis> polymorphisms: a meta-analysis

The objective of the study was to determine by meta-analysis whether polymorphisms of the gene encoding peptidylarginine deiminase 4 (PADI4) are associated with susceptibility to rheumatoid arthritis (RA). A literature review was conducted to identify data sets that described analyses of genetic association between PADI4 polymorphisms and RA. Data sets were collated and a meta-analysis was performed, with a specific focus on associations within Caucasian and Asian populations. A total of 15,947 RA cases and 22,696 controls that were taken from 28 studies in 24 papers were included in this study. Meta-analysis showed a significant association between allele 2 of the PADI4_94 polymorphism and RA in the overall population (odds ratio [OR]?=?1.155, 95 % confidence interval [CI]?=?1.069–1.249, p?=?2.7?×?10^?5). Stratification by ethnicity revealed an association between PADI4_94 allele 2 and RA in Asians (OR?=?1.273, 95 % CI?=?1.193–1.359, p?<?1.0?×?10^?9), but not in Caucasians (OR?=?1.024, 95 % CI?=?0.973–1.078, p?=?0.358). However, meta-analysis using homozygote contrast showed an association between PADI4_94 allele 2 and RA in both Asians (OR?=?2.311, 95 % CI?=?1.1.858–2.875, p?<?1.0?×?10^?9) and Caucasians (OR?=?1.523, 95 % CI?=?1.157–2.004, p?=?0.008). Meta-analysis also revealed an association between allele 2 of the PADI4_104 polymorphism and RA in both Asians (OR?=?1.547, 95 % CI?=?1.247–1.919, p?=?7.1?×?10^?6) and Caucasians (OR?=?1.096, 95 % CI?=?1.025–1.172, p?=?0.008). Finally, meta-analysis showed an association between allele 2 of the PADI4_92 polymorphism and RA in Asians (OR?=?1.263, 95 % CI?=?1.153–1.384, p?=?5.8?×?10^?8), but not in Caucasians (OR?=?1.123, 95 % CI?=?0.980–1.287, p?=?0.095). Meta-analysis indicated no association between allele 2 of either the PADI4_90 or PADI4_89 polymorphisms and RA in Asians. This meta-analysis revealed that the PADI4_94 and PADI_104 polymorphisms are associated with susceptibility to RA in Asians and Caucasians, and that the PADI4_92 polymorphism is associated with susceptibility to RA in Asians, but not in Caucasians.     

Healthcare-Associated Pneumonia and Hospital-Acquired Pneumonia: Bacterial Aetiology,Antibiotic Resistance and Treatment Outcomes: A Study From North India

Background

Data regarding the comparative profiling of HCAP and HAP from developing countries like India are scant. We set out to address the microbial aetiology, antibiotic resistance and treatment outcomes in patients with HCAP and HAP.

Methods

318 consenting patients with HCAP (n?=?165, aged 16–90 years; median 60 years; 97 males) or HAP (n?=?153; aged 16–85 years; median 45 years; 92 males) presenting to a tertiary care hospital in North India from 2013 to 2015 were prospectively recruited for the study. Data on patient characteristics, microbial aetiology, APACHE II scores, treatment outcomes and mortality were studied. Clinical outcomes were compared with various possible predictors employing logistic regression analysis.

Results

Patients in HCAP had more comorbidity. Escherichia coli (30, 18%) and Acinetobacter baumannii (62, 41%) were the most commonly isolated bacteria in HCAP and HAP, respectively. Multidrug-resistant bacteria were isolated more frequently in HCAP, only because the incidence of extensively drug-resistant bacteria was markedly high in HAP (p?=?0.00). The mean APACHE II score was lower in HCAP (17.55?±?6.406, range 30) compared to HAP (19.74?±?8.843, range 37; p?=?0.013). The length of stay?≥?5 days (p?=?0.036) and in-hospital mortality was higher in HAP group (p?=?0.002). The most reliable predictors of in-hospital mortality in HCAP and HAP were APACHE II score?≥?17 (OR?=?14, p?=?0.00; HAP: OR?=?10.8, p?=?0.00), and septic shock (OR?=?4.5, p?=?0.00; HAP: OR?=?6.9, p?=?0.00).

Conclusion

The patient characteristics in HCAP, treatment outcomes, bacterial aetiology, and a higher incidence of antibiotic-resistant bacteria, suggest that HCAP although not as severe as HAP, can be grouped as a separate third entity.

     

Gadolinium-enhanced MRI features of acute gouty arthritis on top of chronic gouty involvement in different joints

The aims of the current study are to describe gadolinium-enhanced MRI features of an acute flare of established gouty arthritis in different joints and to examine a possible association between serum uric acid and MRI signs indicative of ongoing inflammation and/or structural joint damage as well as association with disease characteristics and laboratory findings. Twenty-seven male patients with established chronic gout agreed to participate, mean age 47.6 years, and mean disease duration in months 43.2 (±31.8). For all patients, detailed demographic, disease characteristics, and laboratory findings were obtained and correlated with MRI findings. In 27 patients with established gout, a total of 50 MRI studies were performed of the following joints: feet joints (n?=?23), ankles (n?=?18), knees (n?=?5), and hand and wrist joints (n?=?4). MRI revealed capsular thickening in 19 patients, bone marrow edema (BME) in 15, soft tissue edema (STE) in 20, joint effusion in 21, bone erosions in 17, cartilaginous erosions in 4, and tenosynovitis in 9 cases. In 17 cases, tophaceous lesions were found. Post contrast MRI showed synovial thickening in seven cases. Positive correlations were observed between serum uric acid levels and the following MRI findings: capsular thickening (r?=?0.552, p?=?0.003), BME (r?=?0.668, p?≤?0.0001), STE (r?=?0.559, p?=?0.002), and tenosynovitis (r?=?0.513, p?=?0.006). Using MRI in chronic gout, important features can be detected like BME, minute cartilaginous erosions, and hypertrophic synovial inflammation in post contrast MR images. Serum uric acid (SUA) was positively correlated with capsular thickening, BME, STE, and tenosynovitis.     

Clinical patterns,epidemiology and risk factors of community-acquired urinary tract infection caused by extended-spectrum beta-lactamase producers: a prospective hospital case-control study

Purpose

To assess incidence rate, risk factors and susceptibility patterns associated with extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae in community-acquired urinary tract infections (CA-UTIs).

Methods

A prospective, case-control study was conducted at a tertiary teaching hospital from Jan 2015 to Dec 2016. The results of microbiology cultures were initially screened to include only patients with positive E. coli or K. pneumoniae urine cultures. Afterwards, clinical symptoms were assessed to confirm the UTI. To investigate the risk factors, patients with a positive urine culture for ESBL-producing isolates were assigned as cases, while patients with non-ESBL were assigned as controls.

Results

Out of 591 patients included in this study, 57.5% (n?=?340) were included in the control group and 42.5% (n?=?251) were in the case group. The incidence rate of ESBL-producing isolates was 3.465 cases per 1000-patient hospital admissions. Male gender (OR?=?1.856, 95% CI?=?1.192–2.889, p?=?0.006), pediatrics (OR?=?1.676, 95% CI?=?1.117–2.517, p?=?0.013), patients with comorbidity (OR?=?1.542, 95% CI?=?1.029–2.312, p?=?0.036) and UTI in the previous 12 months (OR?=?1.705, 95% CI?=?1.106–2.628, p?=?0.016) were independently associated with a higher risk of infection. The resistance rate for most commonly prescribed antibiotics was high.

Conclusions

Our results suggest that the incidence of ESBL producers among CA-UTIs is high. Male gender, pediatrics, comorbidity and UTI in the previous 12 months were associated with a higher risk for infection. Continuous surveillance and prudent antibiotic use by healthcare professionals are important factors for effective control of ESBL associated infections.

     

Physiological determinants of walking effort in older adults: should they be targets for physical activity intervention?

Older adults do not get enough physical activity increasing risk for chronic disease and loss of physical function. The purpose of this study was to determine whether neuromuscular, metabolic, and cardiorespiratory indicators of walking effort explain daily activity in community-dwelling older adults. Sixteen women and fourteen men, 78?±?8 years, performed a steady-state walk on a treadmill at 1.25 m s^?1 while muscle activation, heart rate, lactate, respiratory exchange ratio, oxygen consumption (VO₂), ventilation, and rating of perceived exertion (RPE) were recorded as markers of Walking Effort. Daily walking time, sitting/lying time, energy expenditure, and up-down transitions were recorded by accelerometers as markers of Daily Activity. Structural equation modeling was used to explore the relationship between the latent variables Walking Effort and Daily Activity controlling for age and BMI. Participants spent 9.4?±?1.9 h of the waking day sedentary and 1.9?±?0.6 h walking. In the structural equation model, the latent variable Walking Effort explained 64% of the variance in the Daily Activity latent variable (β?=?0.80, p?=?0.004). Walking Effort was identified by heart rate (β?=?0.64), ventilation (β?=?0.88), vastus lateralis activation (β?=?0.49), and lactate (β?=?0.58), all p?<?0.05, but not RPE or VO₂. Daily Activity was identified by stepping time (β?=?0.75) and up-down transitions (β?=?0.52), all p?<?0.05. Walking effort mediated the effects of age and BMI on older adults’ daily activity making physiological determinants of walking effort potential points of intervention.     

Association of HSD11B1 rs12086634 and HSD11B1 rs846910 gene polymorphisms with polycystic ovary syndrome in South Indian women

The 11beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme generates cortisol from cortisone for local glucocorticoid action in hepatocytes and adipocytes. Functional polymorphisms within 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) gene have shown an association with various factors including insulin resistance, diabetes, and obesity. In this study, we have assessed a candidate gene association study in order to examine the association of HSD11B1 gene polymorphisms with polycystic ovary syndrome (PCOS). A total of 200 women were investigated in this case-control study. DNA samples from PCOS women (n?=?100) and the age-matched control women (n?=?100) were analyzed. Genotyping of HSD11B1 rs12086634 and rs846910 variants was performed using tetra-primer amplification refractory mutation system (TETRA-ARMS) PCR. Odds ratio and 95% confidence interval were calculated to determine the association of HSD11B1 gene polymorphisms with polycystic ovary syndrome. The association analysis indicate that HSD11B1 rs12086634 showed positive association with polycystic ovary syndrome (OR?=?1.95; 95%CI?=?1.11–3.44, p?=?0.0195) and women with HSD11B1 rs12086634 TG genotype had significantly higher body mass index (28.05 kg/mt², p?=?0.001), higher waist circumference (89.68 cms, p?=?0.019), higher triglycerides (120.37 mg/dl, p?=?0.049), and lower HDL levels (45.56 mg/dl, p?=?0.004) compared to the women with HSD11B1 TT genotype. HSD11B1 rs846910 did not show any association with PCOS (OR?=?0.57; 95%CI?=?0.311–1.051, p?=?0.072). Our results suggest that HSD11B1 rs12086634 polymorphism is associated with PCOS and HSD11B1 rs846910 gene polymorphism is not associated with PCOS in South Indian women.     

Discordant association of the <Emphasis Type="Italic">CREBRF</Emphasis> rs373863828 A allele with increased BMI and protection from type 2 diabetes in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand

Aims/hypothesis

The A (minor) allele of CREBRF rs373863828 has been associated with increased BMI and reduced risk of type 2 diabetes in the Samoan populations of Samoa and American Samoa. Our aim was to test rs373863828 for associations with BMI and the odds of type 2 diabetes, gout and chronic kidney disease (CKD) in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand.

Methods

Linear and logistic regression models were used to analyse the association of the A allele of CREBRF rs373863828 with BMI, log-transformed BMI, waist circumference, type 2 diabetes, gout and CKD in 2286 adults. The primary analyses were adjusted for age, sex, the first four genome-wide principal components and (where appropriate) BMI, waist circumference and type 2 diabetes. The primary analysis was conducted in ancestrally defined groups and association effects were combined using meta-analysis.

Results

For the A allele of rs373863828, the effect size was 0.038 (95% CI 0.022, 0.055, p?=?4.8?×?10^?6) for log-transformed BMI, with OR 0.59 (95% CI 0.47, 0.73, p?=?1.9?×?10^?6) for type 2 diabetes. There was no evidence for an association of genotype with variance in BMI (p?=?0.13), and nor was there evidence for associations with serum urate (β?=?0.012 mmol/l, p_corrected?=?0.10), gout (OR 1.00, p?=?0.98) or CKD (OR 0.91, p?=?0.59).

Conclusions/interpretation

Our results in New Zealand Polynesian adults replicate, with very similar effect sizes, the association of the A allele of rs373863828 with higher BMI but lower odds of type 2 diabetes among Samoan adults living in Samoa and American Samoa.