Analytical validation and investigation on reference intervals of aldosterone and renin in Chinese Han population by using fully automated chemiluminescence immunoassays

BackgroundThe aldosterone/renin ratio (ARR) is recommended to screen for primary aldosteronism (PA) in hypertension. We estimated fully automated chemiluminescence immunoassays (CLIA) for plasma aldosterone concentrations (PAC) and plasma direct renin concentrations (PRC) and investigated their reference intervals in Chinese Han population.MethodsPAC and PRC were measured on a fully automated analyzer (LIAISON XL, DiaSorin, Italy). Performance characteristics were estimated according to CLSI approved guidelines. 328 healthy individuals were selected for reference intervals investigation. Results simultaneously tested by CLIA and radioimmunoassays were reviewed from 123 patients with hypertension and/or adrenal space-occupying lesion. PAC/PRC ratio (ARR_prc) was compared to PAC/plasma renin activity (PRA) ratio (ARR_pra).ResultsWithin-laboratory imprecision was 5.6%–6.7% for PAC and 3.0%–3.3% for PRC. The LoQ was 72.2 pmol/L for PAC and 1.27 mIU/L for PRC. Linearity was excellent in the range of concentrations between 94 and 2708 pmol/L for PAC and 1.3–461.8 mIU/L for PRC. Interferences of hemoglobin, unconjugated bilirubin and lipaemia could be acceptable, but not of conjugated-bilirubin when renin and aldosterone at low concentrations. The central 95% reference intervals for males: PAC: 76–722 pmol/L, PRC: 3.3–92.7 mIU/L, ARR: 2.2–46.0 pmol/mIU; for females: PAC: 85–1010 pmol/L, PRC: 3.7–99.8 mIU/L, ARR: 3.6–68.4 pmol/mIU. Upper reference limits for ARR of younger and older men were lower than women. ARR_prc and ARR_pra showed almost perfect agreement (kappa = 0.815) for screening PA.ConclusionThe DiaSorin tests are valuable analytical options for PAC and PRC measurements. We recommend sex-specific and age-specific reference intervals of these items should be estimated.     

CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension

ObjectivesAldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure. Polymorphisms in aldosterone-synthase gene (CYP11B2) may associate with heterogeneous aldosterone production and hypertension. Hence, we investigated ? 344T/C, Iw/Ic polymorphisms of CYP11B2, plasma renin activity (PRA) and aldosterone concentration (PAC).Design and methodsConsecutive ethnically-matched 450 hypertensive patients and 360 controls were screened by PCR-RFLP for genotypes and haplotypes; PRA and PAC were measured.ResultsThe Iw/Ic polymorphism distribution differed significantly between the two groups (LRT χ² = 15.8, df = 2, P = 0.000). The mutant allele-Ic and genotype-Ic/Ic were overrepresented in patients (35% versus 27% and 13% versus 7%). Overrepresentation of T-Ic haplotype in patients was identified as risk haplotype (P = 0.000). Patients had significantly higher PAC and aldosterone-to-renin ratio (ARR; P  = 0.000), which was Ic-allele dependent.ConclusionsThe haplotype T-Ic associated with hypertension susceptibility. Correlation between Ic-allele and raised ARR likely serve in hypertension management.     

Progestin-dependent effect of oral contraceptives on plasma aldosterone/renin ratio

ObjectivesEstrogens in oral contraceptives (OC) may influence plasma aldosterone/plasma renin activity (ALD/PRA) and plasma aldosterone/plasma renin concentration (ALD/DRC) ratios, but the effect of progestins on these ratios has not been sufficiently studied so far.Design and methodsPRA (RIA, DiaSorin), DRC and ALD (IRMA, RIA, Beckman Coulter) were measured, then ALD/PRA and ALD/DRC were calculated in 86 healthy normotensive women (aged 27.3 ± 7.5 years), 63 using progestin-containing OC: either gestodene (GTD, n = 25), desogestrel (DSG, n = 22) or drospirenone (DRSP, n = 16). 23 OC-nonusers served as control.ResultsData are presented as median and lower and upper quartiles. PRA, DRC and ALD levels were higher (p < 0.001) in the DRSP group [3.1 (1.5 3.8) ng/mL/h, 25.2 (9.8 30.4) ng/L and 43.7 (28.0 61.6) ng/dL, respectively], than in the DSG [1.4 (1.1 2.1) ng/mL/h, 8.3 (6.8 12.3) ng/L and 11.5 (7.2 16.6) ng/dL], GTD [1.2 (0.8 2.2) ng/mL/h, 8.0 (4.8 10.5) ng/L, and 13.4 (7.7 22.1) ng/dL] and control [1.3 (0.7 1.6) ng/mL/h, 12.2 (7.5 21.7) ng/L, and 10.0 (4.4 14.7) ng/dL] groups. Cases of falsely elevated ALD/PRA and ALD/DRC ratios [7 (11%) and 12 cases (19%) respectively] were only found in OC users but not in the control group. In the DSG and GTD groups, but not in the DRSP group falsely elevated ALD/PRA occurred less frequently than falsely elevated ALD/DRC.ConclusionsIn OC-users falsely elevated ALD/PRA and especially ALD/DRC are a common finding, particularly when the OC contains DSG or GTD. Therefore, for OC-users method- and progestin-type specific cut-off levels should be established.     

Combining body mass index and serum potassium to urine potassium clearance ratio is an alternative method to predict primary aldosteronism

BackgroundThough aldosterone–renin ratio (ARR) is the current routine screening method for suspicious primary aldosteronism, we hypothesized that the simple formula combining body mass index (BMI) and serum potassium to urine potassium clearance (PUKC) ratio was comparable to ARR.MethodsRecords of patients who were referred to the National Taiwan University Hospital for investigation of primary aldosteronism from January 1995 through December 2007 were retrieved. Primary aldosteronism was diagnosed based on the modified 4-corners criteria, otherwise essential hypertension was diagnosed. In both groups, the PUKC/BMI ratio was determined as well as the ARR. Bland–Altman and mountain-plot analysis were used to validate the agreement between ARR and PUKC/BMI. Receiver operating characteristic (ROC) curves were used to compare the sensitivity and specificity of PUKC/BMI and ARR.ResultsThe records for urinary potassium were analyzed for 177 hypertensive patients (134 patients with primary aldosteronism). ROC curves showed comparable areas under the curves of both methods (95% CI: ? 0.029 to 0.183; p = 0.186). Bland–Altman analysis further supported the agreement between ARR and PUKC/BMI ratio.ConclusionsWe found that the screening power of PUKC/BMI was as good as that of conventional ARR. With the quick and extensive availability of the PUKC/BMI method and its equivalence to ARR, this screening strategy would be a good first-line tool for massive community-based primary aldosteronism surveys.     

液相色谱串联质谱法对原发性醛固酮增多症的诊断价值

目的： 探讨液相色谱串联质谱（LC-MS/MS）检测方法中的卡托普利试验（captopril test，CCT）和生理盐水输注试验（saline infusion test，SIT）对原发性醛固酮增多症（primary aldosteronism，PA）的诊断价值。方法： 选取2018年2月至2019年2月复旦大学附属中山医院内分泌科收治的高血压患者127例，其中111例患者行CCT试验，101例患者行SIT试验。通过LC-MS/MS方法检测患者试验前后血浆醛固酮浓度（PAC）、肾素活性及醛固酮/肾素活性比值（aldosterone/renin ratio，ARR）水平。以手术或螺内酯试验为诊断金标准，采用CCT和SIT的ROC曲线探讨2种试验的诊断指标和最佳诊断截断值。结果： PA患者57例，原发性高血压患者70例。CCT后醛固酮、ARR及醛固酮抑制率的AUC分别为0.876、0.902和0.751；ARR为6.5时，诊断PA的灵敏度为94.2%，特异度为78%；PAC为34.8 pg/mL时，诊断PA的灵敏度为75.5%，特异度为93.2%。SIT后醛固酮、ARR及醛固酮抑制率的AUC分别为0.881、0.823和0.652；PAC为24 pg/mL时，诊断PA的灵敏度为87.2%，特异度为78.8%。结论： CCT后ARR和PAC均可作为PA的诊断指标，诊断截断值为6.5和34.8 pg/mL；SIT试验后PAC为PA诊断指标，诊断截断值为24 pg/mL。     

Kidney impairment in primary aldosteronism

BackgroundKidney impairment is noted in primary aldosteronism (PA), and probably initiated by glomerular hyperfiltration.MethodsA prospectively defined survey was conducted on 602 patients who were suspected of PA in the multiple-center Taiwan Primary Aldosteronism Investigation (TAIPAI) database. Estimated glomerular filtration rate (eGFR) was calculated and followed up at 1 yr after treatment.ResultsThe diagnosis of PA was confirmed in 330 patients. Among them 17% of these patients had kidney impairment (eGFR < 60 ml/min/1.73 m²). Patients with PA had a higher prevalence of estimated hyperfiltration than those with essential hypertension (EH) (14.5% vs. 7.0%, p = 0.005). The eGFR independently predicted PA (OR, 1.017) in the propensity-adjusted multivariate logistic model. In PA, plasma renin activity and lower serum potassium (p = 0.018) was correlated with kidney impairment (p = 0.001), while this relationship was not significant in patients with EH. Either unilateral adrenalectomy or treatment of spironolactone for PA patients caused a decrease of eGFR (p < 0.001). Pre-operative hypokalemia (p = 0.013) and the long latency of hypertension (p = 0.016) could enhance the significant decrease of eGFR after adrenalectomy.ConclusionsPatients with aldosteronism had relative estimated hyperfiltration than patients with EH. Calculation of eGFR may increase the specificity in identifying patients with PA. Our findings demonstrate the correlation of serum potassium and renin with estimated hyperfiltration in PA and their relationship to kidney damage. These results provide a high priority for future renal protective strategies and methods for the early diagnosis and prompt treatment of PA.     

醛固酮与肾素活性比值对原发性醛固酮增多症的诊断价值

目的 评价醛固酮与肾素活性比值(ALD/PRA,ARR)对原发性醛固酮增多症(PA)的诊断价值.方法 回顾性收集44例PA、9例嗜铬细胞瘤、8例无功能性瘤、12例库欣综合征、4例肾动脉狭窄及13例原发性高血压患者的ALD、PRA结果,计算ARR,采用受试者操作特性(ROC)曲线评价各项指标的诊断价值.结果 卧位ALD ROC曲线下面积为0.947,临界值(cut-off值)为174.1 ng/L时,敏感度为86.4%,特异度为91.3%.立位ALDROC曲线下面积为0.889,cut-off值为209.8 ng/L时,敏感度为84.1%,特异度为87.0%.卧位ARR ROC曲线下面积为0.978,cut-off值为40.8 ng·dl-1/ng·ml-1·h-1时,敏感度为95.5%,特异度为95.7%;立位ARR ROC曲线下面积为0.981,cut-off值为35.26 ng·dl-1/ng·ml-1·h-1时,敏感度为95.5%,特异度为93.5%;联合立位ARR和立位ALD,其诊断价值明显优于单一指标,当立位ALD>275 ng/L,立位ARR ROC曲线下面积为0.989,cut-off值为23.73 ng·dl-1/ng·ml-1·h-1时,特异度为100%,敏感度为95.7%.结论 ARR诊断PA的价值高于ALD、PRA,立位ARR优于卧位,当联合立位AID>275ng/L,则诊断价值更大.     

The London Chest Activity of Daily Living scale cut-off point to discriminate functional status in patients with chronic obstructive pulmonary disease

ObjectiveTo determine the cut-off point for the London Chest Activity of Daily Living scale in order to better discriminate functional status. Secondarily, to determine which of the scores (total or %total) is better associated with clinical outcomes of a pulmonary rehabilitation program.MethodsSixty-one patients with chronic obstructive pulmonary disease performed the following tests: spirometry; Chronic Obstructive Pulmonary Disease Assessment Test; Saint George's Respiratory Questionnaire; modified Medical Research Council, the body-mass index, airflow obstruction, dyspnea, and exercise capacity index; six-minute walk test; physical activity in daily life assessment and London Chest Activity of Daily Living scale. Thirty-eight patients were evaluated pre- and post-pulmonary rehabilitation . The cut-off point was determined using the receiver operating characteristic curve with six-minute walk test (cut-off point: 82%pred), modified Medical Research Council (cut-off point: 2), level of physical (in)activity (cut-off point: 80 min per day in physical activity ≥3 metabolic equivalent of task) and presence/absence of severe physical inactivity (cut-off point: 4580 steps per day) as anchors.ResultsA cut-off point found for all anchors was 28%: modified Medical Research Council [sensitivity = 83%; specificity = 72%; area under the curve = 0.80]; level of physical (in)activity [sensitivity = 65%; specificity = 59%; area under the curve = 0.67] and classification of severe physical inactivity [sensitivity = 70%; specificity = 62%; area under the curve = 0.70]. The patients who scored ≤28% in %total score of London Chest Activity of Daily Living had lower modified Medical Research Council , Chronic Obstructive Pulmonary Disease Assessment Test, Saint George's Respiratory Questionnaire, body-mass index, airflow obstruction, dyspnea and exercise capacity index and sitting time than who scored >28%, and higher forced expiratory volume in the first second, time in physical activity ≥3 metabolic equivalent of task, steps per day and six-minute walk distance. The %total score of London Chest Activity of Daily Living correlated better with clinical outcomes than the total score.ConclusionsThe cut-off point of 28% is sensitive and specific to distinguish the functional status in patients with chronic obstructive pulmonary disease. The %total score of the London Chest Activity of Daily Living reflects better outcomes of chronic obstructive pulmonary disease when compared to total score.     

Effects of a home-based rehabilitation program in obese type 2 diabetics

ObjectiveTo assess, in obese type 2 diabetics (T2D), the impact of a home-based effort training program and the barriers to physical activity (PA) practice.MethodTwenty-three obese T2D patients (52.7 ± 8.2 years, BMI = 38.5 ± 7.6 kg/m²) were randomized to either a control group (CG), or an intervention group (IG) performing home-based cyclergometer training during 3 months, 30 min/day, with a monthly-supervised session. The initial and final measurements included: maximal graded effort test on cyclergometer, 6-minute walk test (6MWT) and 200-meter fast walk test (200mFWT), quadriceps maximal isometric strength, blood tests and quality of life assessment (SF- 36). A long-term assessment of the amount of physical activity (PA) and the barriers to PA practice was conducted using a questionnaire by phone call.ResultsPatients in the CG significantly improved the maximal power developed at the peak of the cyclergometer effort test (P < 0.05) as well as the quadriceps strength (P < 0.01). There were no significant changes in the other physical and biological parameters, neither in quality of life. At a mean distance of 17 ± 6.4 months, the PA score remained low in the two groups. The main barriers to PA practice identified in both groups were the perception of a low exercise capacity and a poor tolerance to effort, lack of motivation, and the existence of pain associated to PA.ConclusionThis home-based intervention had a positive impact on biometrics and physical ability in the short term in obese T2D patients, but limited effects in the long term. The questionnaires completed at a distance suggest considering educational strategies to increase the motivation and compliance of these patients.     

Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin–angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study

BackgroundAntihypertensive and tissue-protective properties of vitamin D metabolites are increasingly attributed to the inhibition of renin synthesis by 1,25-dihydroxyvitamin D [1,25(OH)2D] in the kidney.MethodWe aimed to document a potential association between 25-hydroxyvitamin D [25(OH)D], 1,25(OH)2D and the circulating renin–angiotensin system (RAS) in a large cohort of patients referred (n = 3316) to coronary angiography.ResultsOf the 3316 subjects, 3296 (median age: 63.5 (56.3–70.6) years; 30.2% women) had a baseline measurement of 25(OH)D [median: 15.6(10.1–23.0) µg/L)], 1,25(OH)2D [median: 33.2(25.2–42.9) pg/mL], plasma renin concentration [PRC; median: 11.4(6.0–24.6) pg/mL] and angiotensin 2 [median: 20.0(12.0–35.0) ng/L]. Multivariate adjusted ANCOVA showed a steady increase of PRC values across declining deciles of 25(OH)D and 1,25(OH)2D values (P = 0.013 and P = 0.045), respectively. Additionally, mean angiotensin 2 values increased significantly across decreasing 25(OH)D and 1,25(OH)2D values (P = 0.020 and P = 0.024, respectively). In contrast, multivariate adjusted ANCOVA revealed no significant associations between aldosterone, aldosterone-to-renin ratio and 25(OH)D/1,25(OH)2D values. In multivariate stepwise regression analyses both, 25(OH)D and 1,25(OH)2D emerged as independent predictors of plasma renin and angiotensin 2 concentrations.ConclusionsOur data showed for the first time in humans that both, lower 25(OH)D and 1,25(OH)2D values are independently related to an upregulated circulating RAS.     

Measurement of pulmonary artery to aorta ratio in computed tomography is correlated with pulmonary artery pressure in critically ill chronic obstructive pulmonary disease patients

AimChronic obstructive pulmonary disease (COPD) is one of the leading chronic diseases and a common cause of death. Identification of COPD patients at high risk for complications and mortality is of utmost importance. Computed tomography (CT) can be used to measure the ratio of the diameter of the pulmonary artery (PA) to the diameter of the aorta (A), and PA/A ratio was shown to be correlated with PA pressure (PAP). However, the prognostic value of PA size remains unclear in patients with COPD. We hypothesized that PA enlargement, as shown by a PA/A ratio greater than 1, could be associated with a higher risk of mortality in COPD patients admitted to the intensive care unit.MethodsData of patients admitted to a medical intensive care unit of a university hospital were retrospectively reviewed between January 2008 and December 2012. Patients who were identified to have a diagnosis of acute exacerbation of COPD and who had an echocardiogram and CT scan were included. Pulmonary artery to aorta ratio was calculated and patients were grouped as PA/A ≤ 1 and PA/A > 1. Comparisons were made between the groups and between patients who died and survived. Correlation analysis, survival analysis, and logistic regression analysis were done, where appropriate.ResultsOne hundred six COPD patients were enrolled. There were 40 (37.4%) patients who had a PA/A > 1. Echocardiography measured PAP was higher in the group with PA/A > 1 than in those with PA/A ≤ 1 (62.1 ± 23.2 mm Hg vs 45.3 ± 17.9 mm Hg, P = .002). Mortality rate of patients with PA/A > 1 was higher (50%) than of those patients with PA/A ≤ 1 (36.4%), although the difference did not reach a statistical significance (P = .17). Correlation was found between vmeasured PA diameter and PAP (r = 0.51, P = .001) as well as between the Acute Physiology and Chronic Health Evaluation II values and PAP (r = 0.25, P = .025).ConclusionThe PA/A ratio is an easily measured method that can be performed on thorax CT scans. Although, we failed to demonstrate a statistically significant association between higher PA/A and increased mortality, PA/A can be used as a surrogate marker to predict the pulmonary hypertension.     

Intra-arrest hypothermia: Both cold liquid ventilation with perfluorocarbons and cold intravenous saline rapidly achieve hypothermia,but only cold liquid ventilation improves resumption of spontaneous circulation

BackgroundRapid intra-arrest induction of hypothermia using total liquid ventilation (TLV) with cold perfluorocarbons improves resuscitation outcome from ventricular fibrillation (VF). Cold saline intravenous infusion during cardiopulmonary resuscitation (CPR) is a simpler method of inducing hypothermia. We compared these 2 methods of rapid hypothermia induction for cardiac resuscitation.MethodsThree groups of swine were studied: cold preoxygenated TLV (TLV, n = 8), cold intravenous saline infusion (S, n = 8), and control (C, n = 8). VF was electrically induced. Beginning at 8 min of VF, TLV and S animals received 3 min of cold TLV or rapid cold saline infusion. After 11 min of VF, all groups received standard air ventilation and closed chest massage. Defibrillation was attempted after 3 min of CPR (14 min of VF). The end point was resumption of spontaneous circulation (ROSC).ResultsPulmonary arterial (PA) temperature decreased after 1 min of CPR from 37.2 °C to 32.2 °C in S and from 37.1 °C to 34.8 °C in TLV (S or TLV vs. C p < 0.0001). Coronary perfusion pressure (CPP) was higher in TLV than S animals during the initial 3 min of CPR. Arterial pO₂ was higher in the preoxygenated TLV animals. ROSC was achieved in 7 of 8 TLV, 2 of 8 S, and 1 of 8 C (TLV vs. C, p = 0.03).ConclusionsModerate hypothermia was achieved rapidly during VF and CPR using both cold saline infusion and cold TLV, but ROSC was higher than control only in cold TLV animals, probably due to better CPP and pO₂. The method by which hypothermia is achieved influences ROSC.     

Predictive value of osteocalcin in bone metastatic differentiated thyroid carcinoma

ObjectivesTo evaluate the diagnostic value of serum osteocalcin in the detection of bone metastases from differentiated thyroid carcinoma (DTC).Design and methodsSerum samples from DTC patients with (DTC BM+, n = 19) or without bone metastases (DTC BM?, n = 19), and matched healthy volunteers (n = 30) were tested for serum osteocalcin with electrochemiluminescent immunoassay.ResultsOsteocalcin was higher in DTC BM+ than in DTC BM? patients (+ 35.8%, p = 0.002), acting as an independent risk factor for bone metastases (R² = 0.142, p = 0.039). The sensitivity was 78.9% and the specificity was 63.2% at a cut-off value of 11.2 μg/L.ConclusionsSerial measurements of osteocalcin could be useful in the detection of bone metastases from DTC.     

Relationship between hyporesponsiveness to clopidogrel measured by thrombelastography and in stent restenosis in patients undergoing percutaneous coronary intervention

ObjectivesThe relationship between hyporesponsiveness to clopidogrel and in stent restenosis (ISR) was analyzed, and the cut-off value of hyporesponsiveness to clopidogrel for ISR was evaluated.Design and methods861 consecutive patients enrolled and patients' inhibition rates in arachidonic acid (AA) and adenosine 5′-diphosphate (ADP) pathways were measured by thrombelastography (TEG) system. Patients were divided into ISR and non-ISR groups according to the results of coronary angiography. Correlation between hyporesponsiveness to clopidogrel and ISR was analyzed.Results249 patients were in ISR group and 612 patients were in non-ISR group. The frequency of clopidogrel hyporesponsiveness in ISR group was significantly higher than that in non-ISR group (P < 0.01). Inhibition rates in AA and ADP pathways in ISR group were lower than those in non-ISR group (P < 0.01). The inhibition rate in ADP pathway was inversely correlated with (r = − 0.225, P = 0.001) the severity of ISR. After being adjusted for traditional covariates, the inhibition rate in ADP pathway (β = − 0.191, R² = 0.011, P = 0.013) remained independently associated with the severity of ISR; clopidogrel hyporesponsiveness was an independent risk factor of ISR (HR 6.62, 95% CI 2.84–15.49, P = 0.001). ROC curve analysis showed that the predictive cut-off value of the inhibition rate in ADP pathway for ISR was 10.1%.ConclusionsThe inhibition rate in ADP pathway is inversely related to the ISR severity. Clopidogrel hyporesponsiveness is an independent risk factor for ISR and can predict the risk of ISR.     

Integrative Review of Nurse-delivered Community-Based Physical Activity Promotion

PurposeThe purpose of this integrative review is to 1) describe intervention attributes, 2) describe the role of nurses in community PA promotion, and 3) describe the efficacy of the interventions in terms of PA behavior change.MethodsComputerized database and ancestry search strategies located distinct intervention trials between 1990 and 2015.ResultsThirteen national and international studies with 2,353 participants were reviewed. Multi-dose, face-to-face, group-based interventions with or without individual-based contacts for 6 months or less were the most common intervention delivery modes. Only 40% (n = 5) of the studies integrated health behavior theory into intervention design. Less than half of the studies demonstrated efficacy in increasing PA.ConclusionsResults suggest that group-based community interventions, such as exercise classes, group walking and group education/counseling, may be more effective in increasing PA compared to individual-based education. Additional rigorously designed studies are warranted to explore the indicators for successful community-based PA promotion.     

Limited effect of a self-management exercise program added to spa therapy for increasing physical activity in patients with knee osteoarthritis: A quasi-randomized controlled trial

BackgroundThe efficacy of spa therapy in osteoarthritis (OA) has ever been demonstrated, with a good level of evidence for pain and disability. The effect of a self-management program with spa therapy on physical activity (PA) level has never been demonstrated.ObjectiveThis study aimed to assess, at 3 months, the effectiveness of 5 sessions of a self-management exercise program in patients with knee OA (KOA) who benefit from 18 days of spa therapy and received an information booklet (on proposed physical exercises) on improvement in at least one PA level.MethodsThis was an interventional, multicentre, quasi-randomized controlled trial with a cluster randomized design (1-month period). People 50 to 75 years old with symptomatic knee OA were included in 3 spa therapy centres in France (Bourbon Lancy, Le Mont Dore, Royat). Both groups received conventional spa therapy sessions during 18 days and an information booklet on the benefits of PA practice for KOA. The intervention group additionally received 5 self-management exercise sessions. The main outcome was improvement in at least one PA level according to the International Physical Activity Questionnaire (IPAQ) short-form categorical score (low to moderate or high, or moderate to high) at 3 months. Secondary outcomes were the evolution of PA (MET-min/week), disability, pain, anxiety, depression, self-efficacy, fears and beliefs concerning KOA, barriers to and facilitators of regular PA practice, consumption of painkillers and adherence to physical exercise program at 3 months. Assessors but not participants or caregivers were blinded.ResultsIn total, 123 patients were randomized, 54 to the intervention group and 69 to the control group. Considering the main outcome, at 3 months, 37% of patients in the intervention group showed improvement in at least one PA level according to the IPAQ categorical score versus 30.4% in the control group (P = 0.44). In the intervention group, 13 (24.1%) patients showed improvement from low to moderate PA level (vs. 8 [11.6%] in the control group), 2 (3.7%) from low to high (vs. 2 [2.9%]) and 5 (9.3%) from moderate to highvs. 11 [15.9%]). Both intervention and control groups showed increased IPAQ continuous scores (MET-min/week) at 3 months, although not significantly. HAD anxiety and depression scores were significantly reduced in the intervention group (P = 0.001 and P = 0.049, respectively) and the perception of PA was better in the intervention than control group for motivation and barriers scores (P = 0.019 and P = 0.002, respectively).ConclusionsThis study showed the lack of impact of a short self-management program on PA level in addition to 18-day spa therapy for KOA, but both intervention and control groups showed improved PA level.     

A ventilation technique for oxygenation and carbon dioxide elimination in CPR: Continuous insufflation of oxygen at three levels of pressure in a pig model

AimPulmonary ventilation remains an important part of cardiopulmonary resuscitation, affecting gas exchange and haemodynamics. We designed and studied an improved method of ventilation for CPR, constructed specifically to support both gas exchange and haemodynamics. This method uses continuous insufflation of oxygen at three levels of pressure, resulting in tri-level pressure ventilation (TLPV). We hypothesized that TLPV improves gas exchange and haemodynamics compared to manual gold standard ventilation (GSV).MethodsIn 14 pigs, ventricular fibrillation was induced and automated CPR performed for 10 min with either TLPV or GSV. After defibrillation, CPR was repeated with the other ventilation method. Gas exchange and haemodynamics were monitored. Data are presented as mean ± standard error of the mean.ResultsTLPV was superior to GSV for PaO₂ (163 ± 36 mmHg difference; P = 0.001), and peak AWP (−20 ± 2 cmH₂O difference; P = 0.000) and higher for mean AWP (8 ± 0.2 cmH₂O difference; P = 0.000). TLPV was comparable to GSV for CPP (5 ± 3 mmHg difference; P = 0.012), VCO₂ (0.07 ± 0.3 mL/min/kg difference; P = 0.001), SvO₂ (4 ± 3%-point; P = 0.001), mean carotid flow (−0.5 ± 4 mL/min difference; P = 0.016), and pH_a (0.00 ± 0.03 difference; P = 0.002). The PaCO₂ data do not provide a conclusive result (4 ± 4 mmHg difference).ConclusionWe conclude that the ventilation strategy with a tri-level pressure cycle performs comparable to an expert, manual ventilator in an automated-CPR swine model.     

Matrix metalloproteinase-1 promoter genotypes and haplotypes are associated with carotid plaque presence

ObjectivesMatrix metalloproteinase (MMP)-1 degrades fibrillar collagens suggesting important role in vascular remodeling. Data about MMP-1 promoter polymorphisms and carotid atherosclerosis (CA) are scarce. The aim of this study was to evaluate association of MMP-1 genotypes/haplotypes with carotid plaque (CP) presence in Serbian population.Design and methodsStudy enrolled a total of 702 participants: 274 controls and 428 consecutive patients with CA who underwent carotid endarterectomy. MMP-1 polymorphisms ? 1607 1G/2G, ? 519 A/G and ? 340 T/C were genotyped by PCR and RFLP methods.ResultsIndividuals carrying MMP-1 ? 1607 2G allele had significantly increased allele dose-dependent risk for CP presence (1G1G vs. 1G2G vs. 2G2G; OR = 1; OR = 1.87 95% CI 1.29–2.07; OR = 3.49 95% CI 1.67–7.30, p = 0.0009, respectively). Compared to the referent haplotype 2G_? 1607-T_? 340-A_? 519, the haplotypes 1G_? 1607-T_? 340-A_? 519, 1G_? 1607-T_? 340-G_? 519 and 2G_? 1607-C_? 340-A_? 519 had statistically significant protective effect on CP presence (OR = 0.41, 95% CI 0.29–0.81, p = 0.01; OR = 0.56, 95% CI 0.44–0.89, p = 0.01; OR = 0.43, 95% CI 0.27–0.86, p = 0.02, respectively).ConclusionsMMP-1 ? 1607 G/2G polymorphism solely and specific haplotypes of three analyzed promoter polymorphisms are significantly and independently associated with occurrence of CP. Replication studies in other populations are needed.     

Detection of serum β2-GPI–Lp(a) complexes in patients with systemic lupus erythematosus

BackgroundCirculating β₂-glycoprotein-I-oxidized low-density lipoprotein (β₂-GPI–ox-LDL) complexes have been found in patients with systemic lupus erythematosus (SLE) and other autoimmune diseases as a contributor to the development of autoimmune-mediated atherosclerosis. In vitro study showed that β₂-GPI also bound with high affinity to atherogenic lipoprotein (a) [Lp(a)] which shares structural similarity to LDL. We examined the existence and clinical significance of serum complexes of β₂-GPI with Lp(a) in SLE patients.MethodsA “sandwich” ELISA was developed for measuring serum concentrations of β₂-GPI–Lp(a) complexes, using rabbit anti-human β₂-GPI antibody as capturing antibody, and quantitating with antibody against apo(a). Forty-seven SLE patients and 42 healthy controls were studied.ResultsBoth Lp(a) (400 ± 213 mg/l vs. 181 ± 70 mg/l) and ox-Lp(a) (27.07 ± 22.30 mg/l vs. 8.20 ± 4.55 mg/l) concentrations were higher in SLE patients than in controls (P < 0.0001). β₂-GPI–Lp(a) complexes were detectable in both controls and SLE. The complexes levels in SLE were higher than in controls (0.96 ± 0.41 U/ml vs. 0.59 ± 0.20 U/ml, P < 0.0001) and was positively correlated with ox-Lp(a) (P < 0.001).ConclusionsWe report the existence of β₂-GPI–Lp(a) complexes in both controls and SLE patients. The complexes levels increase in SLE.     

Dysregulation of TH type cytokines in the patients of Parthenium induced contact dermatitis

BackgroundParthenium contact dermatitis is a major health problem caused by a cosmopolitan weed Parthenium hysterophorus. It is a T cell-mediated immune injury and disease manifests as itchy erythematous papules, papulovesicular and plaque lesions on exposed areas of the body. We studied the involvement of T_H1/T_H2/T_H17/Treg type responses by assaying various cytokines in Parthenium dermatitis.MethodsThe study includes 50 patients of Parthenium dermatitis confirmed by patch testing and 50 healthy subjects. The serum levels of T_H1, T_H2, T_H17 and Treg cytokines were estimated by high sensitivity sandwich ELISA and were compared statistically between groups using ANOVA.ResultsThe mean concentration of T_H1 cytokines (p < 0.001) and IL-17 (p < 0.001) were increased significantly as compared to controls. In contrast, decrease in levels of IL-10 (p < 0.002) and TGF-β (p < 0.001) were significant and levels of IL-4 (p < 0.262) were insignificant whereas no alterations in the total IgE concentrations (p < 0.976) was observed.ConclusionThe induction of T_H1 and T_H17 cytokines reinforce the need of detailed analysis of immune dysregulation in Parthenium dermatitis and might add some insight in the pathogenesis, diagnosis and current treatment modalities of this disease.