Bone marrow lesions predict site-specific cartilage defect development and volume loss: a prospective study in older adults

Introduction

Recent evidence suggests that bone marrow lesions (BMLs) play a pivotal role in knee osteoarthritis (OA). The aims of this study were to determine: 1) whether baseline BML presence and/or severity predict site-specific cartilage defect progression and cartilage volume loss; and 2) whether baseline cartilage defects predict site-specific BML progression.

Methods

A total of 405 subjects (mean age 63 years, range 52 to 79) were measured at baseline and approximately 2.7 years later. Magnetic resonance imaging (MRI) of the right knee was performed to measure knee cartilage volume, cartilage defects (0 to 4), and BMLs (0 to 3) at the medial tibial (MT), medial femoral (MF), lateral tibial (LT), and lateral femoral (LF) sites. Logistic regression and generalized estimating equations were used to examine the relationship between BMLs and cartilage defects and cartilage volume loss.

Results

At all four sites, baseline BML presence predicted defect progression (odds ratio (OR) 2.4 to 6.4, all P < 0.05), and cartilage volume loss (-0.9 to -2.9% difference per annum, all P < 0.05) at the same site. In multivariable analysis, there was a significant relationship between BML severity and defect progression at all four sites (OR 1.8 to 3.2, all P < 0.05) and BML severity and cartilage volume loss at the MF, LT, and LF sites (β -22.1 to -42.0, all P < 0.05). Additionally, baseline defect severity predicted BML progression at the MT and LF sites (OR 3.3 to 3.7, all P < 0.01). Lastly, there was a greater increase in cartilage volume loss at the MT and LT sites when both larger defects and BMLs were present at baseline (all P < 0.05).

Conclusions

Baseline BMLs predicted site-specific defect progression and cartilage volume loss in a dose-response manner suggesting BMLs may have a local effect on cartilage homeostasis. Baseline defects predicted site-specific BML progression, which may represent increased bone loading adjacent to defects. These results suggest BMLs and defects are interconnected and play key roles in knee cartilage volume loss; thus, both should be considered targets for intervention.     

Evaluation of bone marrow lesion volume as a knee osteoarthritis biomarker - longitudinal relationships with pain and structural changes: data from the Osteoarthritis Initiative

Introduction

Bone marrow lesion (BML) size may be an important imaging biomarker for osteoarthritis-related clinical trials and reducing BML size may be an important therapeutic goal. However, data on the interrelationships between BML size, pain, and structural progression are inconsistent and rarely examined in the same cohort. Therefore, we evaluated the cross-sectional and longitudinal associations of BML volume with knee pain and joint space narrowing (JSN).

Methods

A BML volume assessment was performed on magnetic resonance images of the knee collected at the 24- and 48-month Osteoarthritis Initiative visits from a convenience sample of 404 participants in the progression cohort. During the same visits, knee pain was assessed with WOMAC pain scores and knee radiographs were acquired and scored for JSN. BML volume was summed to generate a total knee volume and an index tibiofemoral compartment volume (compartment with greater baseline JSN). Primary analyses included multiple linear regressions (outcome = pain, predictor = total knee BML volume) and logistic regressions (outcome = JSN, predictor = index tibiofemoral compartment BML volume).

Results

This sample was 49% female with a mean age of 63 (9.2 standard deviation (SD)) years, and 71% had radiographic osteoarthritis in the study knee. Larger baseline BMLs were associated with greater baseline knee pain (P = 0.01), the presence of JSN at baseline (odds ratio (OR) = 1.50, 95% confidence interval (CI) = 1.23 to 1.83), and JSN progression (OR = 1.27, 95%CI = 1.11 to 1.46). Changes in total knee BML volume had a positive association with changes in knee pain severity (P = 0.004) and this association may be driven by knees that were progressing from no or small baseline BMLs to larger BMLs. In contrast, we found no linear positive relationship between BML volume change and JSN progression. Instead, regression of medial tibiofemoral BML volume was associated with JSN progression compared to knees with no or minimal changes in BML volume (OR = 3.36, 95%CI = 1.55 to 7.28). However, follow-up analyses indicated that the association between JSN progression and BML volume change may primarily be influenced by baseline BML volume.

Conclusion

Large baseline BMLs are associated with greater baseline knee pain, the presence of JSN at baseline, and disease progression. Additionally, BML regression is associated with decreased knee pain but not a reduced risk of concurrent JSN progression.     

The clinical significance,natural history and predictors of bone marrow lesion change over eight years

Introduction

There is increasing evidence to suggest that bone marrow lesions (BMLs) play a key role in the pathogenesis of osteoarthritis (OA). However, there is a lack of long term data. The aim of this study was to describe the natural history of knee BMLs, their association with knee pain and examine predictors of BML change over eight years.

Methods

A total of 198 subjects (109 adult offspring of subjects who had a knee replacement and 89 community-based controls) were studied. Knee pain and BML size were assessed at two and ten year visits.

Results

At the two year visit, 64% of participants (n = 127) had 229 BMLs (34% patella, 26% femoral and 40% tibial). Over eight years, 24% (55/229) increased in size, 55% (125/229) remained stable and 21% (49/229) decreased in size or resolved completely. Of the participants without BMLs at baseline, 52% (37/71) developed incident BMLs.After adjusting for confounders, eight year change in total BML size was associated with change in knee pain in offspring (β = 2.50, 95% confidence interval (CI) 0.96 to 4.05) but not controls. This association was stronger in males. Incident BMLs were associated with increase in pain (β = 3.60, 95% CI 1.14 to 6.05). Body mass index (BMI) and strenuous activity (but not radiographic osteoarthritis or smoking) were associated with an increase in BML size.

Conclusion

In this midlife cohort, the proportion of BMLs increasing in size was similar to those decreasing in size with the majority remaining stable. Change in BMLs was predicted by BMI and strenuous activity. An increase in BML size or a new BML resulted in an increase in pain especially in males and those with a family history of OA.     

Promising potential of new generation translocator protein tracers providing enhanced contrast of arthritis imaging by positron emission tomography in a rat model of arthritis

Introduction

The role of popliteal cysts and subgastrocnemius bursitis in knee joint homeostasis is uncertain. The aim of this study is to describe cross-sectional associations between popliteal cysts, subgastrocnemius bursitis, knee symptoms and structural abnormalities in older adults.

Methods

A cross-sectional sample of 900 randomly-selected subjects (mean age 63 years, 48% female) were studied. Knee pain, stiffness and dysfunction were assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic knee osteophyte and joint space narrowing (JSN) were recorded. Magnetic resonance imaging (MRI) was utilized to assess popliteal cysts, subgastrocnemius bursitis, cartilage defects and bone marrow lesions (BMLs).

Results

Popliteal cysts were present in 11.7% and subgastrocnemius bursitis in 12.7% of subjects. Subgastrocnemius bursitis was more common in those with popliteal cyst (36.2% versus 9.7%, P <0.01). In multivariable analyses, popliteal cysts were significantly associated with increased osteophytes in both medial and lateral tibiofemoral compartments while subgastrocnemius bursitis was associated with increased osteophytes and JSN in the medial tibiofemoral compartment. Both were significantly associated with cartilage defects in all compartments, and with BMLs in the medial tibiofemoral compartment. Furthermore, both popliteal cysts and subgastrocnemius bursitis were significantly associated with increased weight-bearing knee pain but these associations became non-significant after adjustment for cartilage defects and BMLs.

Conclusions

Popliteal cysts and subgastrocnemius bursitis are associated with increased symptoms as well as radiographic and MRI-detected joint structural abnormalities. Longitudinal data will help resolve if they are a consequence or a cause of knee joint abnormalities.     

Bone marrow lesion volume reduction is not associated with improvement of other periarticular bone measures: data from the Osteoarthritis Initiative

Introduction

We evaluated the associations between bone marrow lesion (BML) volume change and changes in periarticular bone mineral density (paBMD) as well as subchondral sclerosis to determine whether BML change is associated with other local bone changes.

Methods

The convenience sample comprised participants in the Osteoarthritis Initiative (OAI) with weight-bearing posterior-anterior knee radiographs and magnetic resonance images (MRIs) at the 24- and 48-month visits and dual-energy x-ray absorptiometry (DXA) at the 30-/36-month and 48-month visits. The right knee was assessed unless contraindicated for MRI. We used knee DXA scans to measure medial tibia paBMD and medial/lateral paBMD ratio (M:L paBMD). Knee radiographs were scored for sclerosis (grades 0 to 3) in the medial tibia. Two raters determined BML volume on sagittal fat-suppressed MRI by using a semiautomated segmentation method. To focus on knees with only medial tibia BML changes, knees with lateral tibial BMLs were excluded. Medial tibial BML volume change was classified into three groups: BML regression (lowest quartile of medial tibial BML volume change), no-to-minimal change (middle two quartiles), and BML progression (highest quartile). We used proportional odds logistic regression models to evaluate the association between quartiles of changes in medial paBMD or M:L paBMD ratio, as outcomes, and BML volume change.

Results

The sample (n = 308) included 163 (53%) female subjects, 212 (69%) knees with radiographic osteoarthritis, and participants with a mean age of 63.8 ± 9.3 years and mean body mass index of 29.8 ± 4.7 kg/m². We found an association between greater increases in medial tibia paBMD and BML regression (OR = 1.7 (95% confidence interval (CI) = 1.1 to 2.8)) and a similar trend for BML progression (OR = 1.6 (95% CI = 1.0 to 2.6]). We also detected associations between greater increase in M:L paBMD and BML regression (OR = 1.6 (95% CI = 1.0 to 2.7]) and BML progression (OR = 1.8 (95% CI = 1.1 to 3.0)), although BML regression had borderline statistical significance. The frequency of sclerosis progression in the medial tibia (n = 14) was greater among knees with BML progression or regression compared with knees without BML change (P = 0.01 and P = 0.04, respectively).

Conclusion

BML regression and BML progression are characterized by concurrent increases in paBMD and sclerosis, which are characteristic of increased radiographic osteoarthritis severity. At least during 24 months, BML regression is not representative of improvement in other periarticular bone measures.     

Home-based exercise rehabilitation in addition to specialist heart failure nurse care: design, rationale and recruitment to the Birmingham Rehabilitation Uptake Maximisation study for patients with congestive heart failure (BRUM-CHF): a randomised controlled trial

Background

We aimed to assess whether we could identify a graded association between increasing number of components of the metabolic syndrome and cardiac structural and functional abnormalities independently of predicted risk of coronary heart disease by the Framingham risk score.

Methods

We conducted a cross-sectional study on a random sample of the urban population of Porto aged 45 years or over. Six hundred and eighty-four participants were included. Data were collected by a structured clinical interview with a physician, ECG and a transthoracic M-mode and 2D echocardiogram. The metabolic syndrome was defined according to ATPIII-NCEP. The association between the number of features of the metabolic syndrome and the cardiac structural and functional abnormalities was assessed by 3 multivariate regression models: adjusting for age and gender, adjusting for the 10-year predicted risk of coronary heart disease by Framingham risk score and adjusting for age, gender and systolic blood pressure.

Results

There was a positive association between the number of features of metabolic syndrome and parameters of cardiac structure and function, with a consistent and statistically significant trend for all cardiac variables considered when adjusting for age and gender. Parameters of left ventricular geometry patterns, left atrial diameter and diastolic dysfunction maintained this trend when taking into account the 10-year predicted risk of coronary heart disease by the Framingham score as an independent variable, while left ventricular systolic dysfunction did not. The prevalence of left ventricular diastolic dysfunction, and the mean left ventricular mass, left ventricular diameter and left atrial diameter increased significantly with the number of features of the metabolic syndrome when additionally adjusting for systolic blood pressure as a continuous variable.

Conclusion

Increasing severity of metabolic syndrome was associated with increasingly compromised structure and function of the heart. This association was independent of Framingham risk score for indirect indices of diastolic dysfunction but not systolic dysfunction, and was not explained by blood pressure level.     

An in vivo model of a mechanically-induced bone marrow lesion

Bone marrow lesions (BMLs) are radiologic abnormalities in magnetic resonance images of subchondral bone that are correlated with osteoarthritis. Little is known about the physiologic processes within a BML, although BMLs are associated with mechanical stress, bone tissue microdamage and increased bone remodeling. Here we establish a rabbit model to study the pathophysiology of BMLs. We hypothesized that in vivo loads that generate microdamage in cancellous bone would also create BMLs and increase bone remodeling. In vivo cyclic loading (0.2–2.0 MPa in compression for 10,000 cycles at 2 Hz) was applied to epiphyseal cancellous bone in the distal femurs of New Zealand white rabbits (n = 3, right limb loaded, left limb controls experienced surgery but no loading). Magnetic resonance images were collected using short tau inversion recovery (STIR) and T1 weighted sequences at 1 and 2 weeks after surgery/loading and histological analysis of the BML was performed after euthanasia to examine tissue microdamage and remodeling. Loaded limbs displayed BMLs while control limbs showed only a small BML-like signal caused by surgery. Histological analysis of the BML at 2 weeks after loading showed increased tissue microdamage (p = 0.03) and bone resorption (p = 0.01) as compared to controls. The model described here displays the hallmarks of load-induced BMLs, supporting the use of the model to examine changes in bone during the development, progression and treatment of BMLs.     

Reduced trabecular bone mineral density and cortical thickness accompanied by increased outer bone circumference in metacarpal bone of rheumatoid arthritis patients: a cross-sectional study

Introduction

The objective of this study was to assess three-dimensional bone geometry and density at the epiphysis and shaft of the third meta-carpal bone of rheumatoid arthritis (RA) patients in comparison to healthy controls with the novel method of peripheral quantitative computed tomography (pQCT).

Methods

PQCT scans were performed in 50 female RA patients and 100 healthy female controls at the distal epiphyses and shafts of the third metacarpal bone, the radius and the tibia. Reproducibility was determined by coefficient of varia-tion. Bone densitometric and geometric parameters were compared between the two groups and correlated to disease characteristics.

Results

Reproducibility of different pQCT parameters was between 0.7% and 2.5%. RA patients had 12% to 19% lower trabecular bone mineral density (BMD) (P ≤ 0.001) at the distal epiphyses of radius, tibia and metacarpal bone. At the shafts of these bones RA patients had 7% to 16% thinner cortices (P ≤ 0.03). Total cross-sectional area (CSA) at the metacarpal bone shaft of pa-tients was larger (between 5% and 7%, P < 0.02), and relative cortical area was reduced by 13%. Erosiveness by Ratingen score correlated negatively with tra-becular and total BMD at the epiphyses and shaft cortical thickness of all measured bones (P < 0.04).

Conclusions

Reduced trabecular BMD and thinner cortices at peripheral bones, and a greater bone shaft diameter at the metacarpal bone suggest RA spe-cific bone alterations. The proposed pQCT protocol is reliable and allows measuring juxta-articular trabecular BMD and shaft geometry at the metacarpal bone.     

Infrapatellar fat pad in the knee: is local fat good or bad for knee osteoarthritis?

Introduction

Recent studies regarding the infrapatellar fat pad (IPFP) mainly focus on the roles of the cells derived from the IPFP. There have been few clinical or epidemiological studies reporting on the association between the IPFP and knee osteoarthritis (OA). Our objective is to generate hypotheses regarding the associations between IPFP maximum area and knee OA measures in older adults.

Methods

A total of 977 subjects between 50 and 80 years of age (mean, 62.4 years) participated in the study. Radiographic knee osteophyte and joint space narrowing (JSN) were assessed using the Osteoarthritis Research Society International atlas. T1- or T2-weighted fat suppressed magnetic resonance imaging (MRI) was utilized to assess IPFP maximum area, cartilage volume, cartilage defects, and bone marrow lesions (BMLs). Knee pain was assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire.

Results

After adjustment for potential confounders, IPFP maximum area was significantly associated with joint space narrowing (odds ratio (OR): 0.75, 95% confidence interval (CI): 0.62 to 0.91 (medial), 0.77, 95% CI: 0.62 to 0.96 (lateral)) and medial osteophytes (OR: 0.52, 95% CI: 0.35 to 0.76), knee tibial and patellar cartilage volume (β: 56.9 to 164.9 mm³/cm², all P <0.001), tibial cartilage defects (OR: 0.58, 95% CI: 0.41 to 0.81 (medial), 0.53, 95% CI: 0.40-0.71 (lateral)), any BMLs (OR: 0.77, 95% CI: 0.63 to 0.94), and knee pain on a flat surface (OR: 0.79, 95% CI: 0.63 to 0.98). IPFP maximum area was negatively, but not significantly, associated with femoral cartilage defects, lateral tibiofemoral BMLs, and total knee pain or other knee pain subscales.

Conclusion

IPFP maximum area is beneficially associated with radiographic OA, MRI structural pathology and knee pain on a flat surface suggesting a protective role for IPFP possibly through shock absorption. Consequently, we must pay special attention to IPFP in the clinical settings, avoiding resection of normal IPFP in knee surgery.     

Fruit and Vegetable Consumption and Cardiovascular Risk Factors in Older Chinese: The Guangzhou Biobank Cohort Study

Objective

To examine the adjusted associations of fruit consumption and vegetable consumption with the Framingham score and its components in the non-Western setting of Southern China, considering health status.

Method

Linear regression was used to assess the cross-sectional associations of fruit and vegetable consumption with the Framingham score and its components, among 19,518 older Chinese (≥50 years) from the Guangzhou Biobank Cohort Study in Southern China (2003–2006), and whether these differed by health status.

Results

The association of fruit consumption with the Framingham score varied by health status (P-value<0.001), but not vegetable consumption (P-value 0.51). Fruit consumption was associated with a lower Framingham score (-0.04 per portions/day, 95% confidence interval (CI) -0.08 to -0.004) among participants in poor health, adjusted for age, sex, recruitment phase, socio-economic position and lifestyle. However, similarly adjusted, fruit consumption was associated with a higher Framingham score (0.05, 95% CI 0.02 to 0.09) among participants in good health, perhaps due to a positive association of fruit consumption with fasting glucose. Similarly adjusted, vegetable consumption was associated with a higher Framingham score (0.03, 95% CI 0.01 to 0.05) among all participants, with no difference by health status.

Conclusion

This large study from a non-western setting found that fruit and vegetable consumption was barely associated with the Framingham score, or major CVD risk factors.     

Perioperative risk stratification in non cardiac surgery: role of pharmacological stress echocardiography

Background

Mitral annular calcification (MAC) and aortic annular calcification (AVC) may represent a manifestation of generalized atherosclerosis in the elederly. Alterations in vascular structure, as indexed by the intima media thickness (IMT), are also recognized as independent predictors of adverse cardiovascular outcomes.

Aim

To examine the relationship between the degree of calcification at mitral and/or aortic valve annulus and large artery structure (thickness).

Methods

We evaluated 102 consecutive patients who underwent transthoracic echocardiography and carotid artery echoDoppler for various indications; variables measured were: systemic blood pressure (BP), pulse pressure (PP=SBP-DBP), body mass index (BMI), fasting glucose, total, HDL, LDL chlolesterol, triglycerides, cIMT. The patients were divided according to a grading of valvular/annular lesions independent scores based on acoustic densitometry: 1 = annular/valvular sclerosis/calcification absence; 2 = annular/valvular sclerosis; 3 = annular calcification; 4 = annular-valvular calcification; 5 = valvular calcification with no recognition of the leaflets.

Results

Patient score was the highest observed for either valvular/annulus. Mean cIMT increased linearly with increasing valvular calcification score, ranging from 3.9 ± 0.48 mm in controls to 12.9 ± 1.8 mm in those subjects scored 5 (p < 0.0001). In the first to fourth quartile of cIMT values the respective maximal percentual of score were: score 1: 76.1%, score 2: 70.1%, score 4: 54.3% and score 5: 69.5% (p > 0.0001).

Conclusion

MAC and AVC score can identify subgroups of patients with different cIMT values which indicate different incidence and prevalence of systemic artery diseases. This data may confirm MAC-AVC as a useful important diagnostic parameter of systemic atherosclerotic disease.     

Traumeel S® for pain relief following hallux valgus surgery: a randomized controlled trial

Background

In spite of recent advances in post-operative pain relief, pain following orthopedic surgery remains an ongoing challenge for clinicians. We examined whether a well known and frequently prescribed homeopathic preparation could mitigate post-operative pain.

Method

We performed a randomized, double blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S^® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery.

Results

Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04).

Conclusions

Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance.

Trial Registration

This study was registered at ClinicalTrials.gov. # NCT00279513     

The Asp298 allele of endothelial nitric oxide synthase is a risk factor for myocardial infarction among patients with type 2 diabetes mellitus

Background

To establish an efficient prophylaxis of coronary artery disease reliable risk stratification is crucial, especially in the high risk population of patients suffering from diabetes mellitus. This prospective study determined the predictive value of coronary calcifications for future cardiovascular events in asymptomatic patients with diabetes mellitus.

Methods

We included 716 patients suffering from diabetes mellitus (430 men, 286 women, age 55.2 ± 15.2 years) in this study. On study entry all patients were asymptomatic and had no history of coronary artery disease. In addition, all patients showed no signs of coronary artery disease in ECG, stress ECG or echocardiography. Coronary calcifications were determined with the Imatron C 150 XP electron beam computed tomograph. For quantification of coronary calcifications we calculated the Agatston score. After a mean observation period of 8.1 ± 1.1 years patients were contacted and the event rate of cardiac death (CD) and myocardial infarction (MI) was determined.

Results

During the observation period 40 patients suffered from MI, 36 patients died from acute CD. The initial Agatston score in patients that suffered from MI or died from CD (475 ± 208) was significantly higher compared to those without cardiac events (236 ± 199, p < 0.01). An Agatston score above 400 was associated with a significantly higher annualised event rate for cardiovascular events (5.6% versus 0.7%, p < 0.01). No cardiac events were observed in patients with exclusion of coronary calcifications. Compared to the Framingham risk score and the UKPDS score the Agatston score showed a significantly higher diagnostic accuracy in the prediction of MI with an area under the ROC curve of 0.77 versus 0.68, and 0.71, respectively, p < 0.01.

Conclusion

By determination of coronary calcifications patients at risk for future MI and CD could be identified within an asymptomatic high risk group of patients suffering from diabetes mellitus. On the other hand future events could be excluded in patients without coronary calcifications.     

Symptomatic pectus excavatum in seniors (SPES): a cardiovascular problem?: A prospective cardiological study of 42 senior patients with a symptomatic pectus excavatum

Objectives

There is no consensus among physicians as to whether or not pectus excavatum can produce symptoms sometimes even severe enough to justify a surgical procedure. The aim of this study was to assess the prevalence and severity of complaints and symptoms of senior patients with a pectus excavatum and to evaluate the results of surgical correction of the chest deformation.

Design

This is a prospective clinical study, case series.

Participants

The participants are 42 senior patients with a pectus excavatum and somatic complaints.

Methods

Cardiological screening included medical history taking, physical examination, electrocardiography, transthoracic echocardiography and treadmill cardiography. Complaints, symptoms and test results were arranged in a clinical score. Indication for a therapeutic surgical correction by a modified Ravitch operation was a high clinical score in combination with radiological evidence of cardiac compression on CT or MRI.

Results

The clinical picture of the 42 senior patients with a pectus excavatum showed complaints of fatigue and low exercise tolerance, shortness of breath, palpitations, inspiratory obstruction and sometimes chest discomfort or pain. The serious and sometimes invalidating complaints of 19 patients (45%) had started only in their fourth or fifth decade of life and were labelled in 12 patients (63%) as ‘Unexplained cardiovascular complaints’. To date, 11 patients have undergone surgical procedures. Symptoms were reduced substantially or had disappeared completely. All patients indicated that their health-related quality of life was significantly improved.

Conclusion

Recognising the clinical picture of SPES is relevant because surgical reconstruction of the chest can provide substantial relief of symptoms.     

Microdistribution of major to trace elements between roots of Halimione portulacoides and host sediments (Tagus estuary marsh,Portugal)

Aim

This study presents a micrometre-scale map of the elemental distribution within roots and surrounding sediment of Halimione portulacoides of a contaminated salt marsh in the Tagus estuary.

Methods

Microprobe particle induced X-ray emission analysis was performed in sediment slices containing roots with tubular rhizoconcretions attached to host sediments.

Results

Strong concentration gradients were found particularly in the inner part of rhizoconcretions adjacent to the root wall. Local enrichment was observed in sediment interstices with Fe precipitates and other associated elements. A maximum of 55 % of Fe was measured near the concretion–root interface, with a decrease to <5 % in the host sediment. Maximum concentrations of P (3 %), As (1,200 μg g^?1) and Zn (3,000 μg g^?1) were registered in concretions, one order of magnitude above the values of the host sediment. The elemental concentration profiles across roots showed that the epidermis was an efficient selective barrier to the entrance of elements. Fe and As were retained in the epidermis. The highest Cu and Zn concentrations were also observed in the epidermis. However, the concentrations of Mn, Cu and Zn increased in the inner root.

Conclusions

As and Fe were mostly retained in the concretion, whereas P, Mn, Cu and Zn were mobilised by the root.     

The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance

Background

Type 2 diabetes mellitus (T2DM) patients are at increased risk of developing cardiovascular events. Unfortunately traditional risk assessment scores, including the Framingham Risk Score (FRS), have only modest accuracy in cardiovascular risk prediction in these patients.

Methods

We sought to determine the prognostic values of different non-invasive markers of atherosclerosis, including brachial artery endothelial function, carotid artery atheroma burden, ankle-brachial index, arterial stiffness and computed tomography coronary artery calcium score (CACS) in 151 T2DM Chinese patients that were identified low-intermediate risk from the FRS recalibrated for Chinese (<20% risk in 10?years). Patients were prospectively followed-up and presence of atherosclerotic events documented for a mean duration of 61?±?16?months.

Results

A total of 17 atherosclerotic events in 16 patients (11%) occurred during the follow-up period. The mean FRS of the study population was 5.0?±?4.6% and area under curve (AUC) from receiver operating characteristic curve analysis for prediction of atherosclerotic events was 0.59?±?0.07 (P?=?0.21). Among different vascular assessments, CACS?>?40 had the best prognostic value (AUC 0.81?±?0.06, P?<?0.01) and offered significantly better accuracy in prediction compared with FRS (P?=?0.038 for AUC comparisons). Combination of FRS with CACS or other surrogate vascular markers did not further improve the prognostic values over CACS alone. Multivariate Cox regression analysis identified CACS?>?40 as an independent predictor of atherosclerotic events in T2DM patients (Hazards Ratio 27.11, 95% Confidence Interval 3.36-218.81, P?=?0.002).

Conclusions

In T2DM patients identified as low-intermediate risk by the FRS, a raised CACS?>?40 was an independent predictor for atherosclerotic events.     

Effects of aerobic exercise therapy and cognitive behavioural therapy on functioning and quality of life in amyotrophic lateral sclerosis: protocol of the FACTS-2-ALS trial

Background

Neuropathic pain must be correctly diagnosed for optimal treatment. The questionnaire named Neuropathic Pain Symptom Inventory (NPSI) was developed in its original French version to evaluate the different symptoms of neuropathic pain. We hypothesized that the NPSI might also be used to differentiate neuropathic from non-neuropathic pain.

Methods

We translated the NPSI into German using a standard forward-backward translation and administered it in a case-control design to patients with neuropathic (n = 68) and non-neuropathic pain (headache and osteoarthritis, n = 169) to validate it and to analyze its discriminant properties, its sensitivity to change, and to detect neuropathic pain subgroups with distinct profiles.

Results

Using a sum score (the NPSI-G score), we found sensitivity to change (r between 0.37 and 0.5 for pain items of the graded chronic pain scale) and could distinguish between neuropathic and other pain on a group basis, but not for individual patients. Post hoc development of a discriminant score with optimized diagnostic properties to distinguish neuropathic pain from non-neuropathic pain resulted in an instrument with high sensitivity (91%) and acceptable specificity (70%). We detected six different pain profiles in the patient group with neuropathic pain; three profiles were found to be distinct.

Conclusions

The NPSI-G potentially combines the properties of a diagnostic tool and an instrument to identify subtypes of neuropathic pain.     

Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results

Introduction

Second-generation autologous chondrocyte implantation with scaffolds stabilizing the grafts is a clinically effective procedure for cartilage repair. In this ongoing prospective observational case report study, we evaluated the effectiveness of BioSeed^®-C, a cell-based cartilage graft based on autologous chondrocytes embedded in fibrin and a stable resorbable polymer scaffold, for the treatment of clinical symptomatic focal degenerative defects of the knee.

Methods

Clinical outcome after 4-year clinical follow-up was assessed in 19 patients with preoperatively radiologically confirmed osteoarthritis and a Kellgren-Lawrence score of 2 or more. Clinical scoring was performed before implantation of the graft and 6, 12, and 48 months after implantation using the Lysholm score, the Knee injury and Osteoarthritis Outcome Score (KOOS), the International Knee Documentation Committee (IKDC) score, and the International Cartilage Repair Society (ICRS) score. Cartilage regeneration and articular resurfacing were assessed by magnetic resonance imaging (MRI) 4 years after implantation of the autologous cartilage graft.

Results

Significant improvement (P < 0.05) of the Lysholm and ICRS scores was observed as early as 6 months after implantation of BioSeed^®-C and remained stable during follow-up. The IKDC score showed significant improvement compared with the preoperative situation at 12 and 48 months (P < 0.05). The KOOS showed significant improvement in the subclasses pain, activities of daily living, and knee-related quality of life 6 months as well as 1 and 4 years after implantation of BioSeed^®-C in osteoarthritic defects (P < 0.05). MRI analysis showed moderate to complete defect filling with a normal to incidentally hyperintense signal in 16 out of 19 patients treated with BioSeed^®-C. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years.

Conclusions

The results show that the good clinical outcome achieved 1 year after implantation of BioSeed^®-C remains stable over the course of a period of 4 years and suggest that implanting BioSeed^®-C is a promising treatment option for the repair of focal degenerative defects of the knee.     

Popliteal cysts and subgastrocnemius bursitis are associated with knee symptoms and structural abnormalities in older adults: a cross-sectional study

Introduction

The role of popliteal cysts and subgastrocnemius bursitis in knee joint homeostasis is uncertain. The aim of this study is to describe cross-sectional associations between popliteal cysts, subgastrocnemius bursitis, knee symptoms and structural abnormalities in older adults.

Methods

A cross-sectional sample of 900 randomly-selected subjects (mean age 63 years, 48% female) were studied. Knee pain, stiffness and dysfunction were assessed by self-administered Western Ontario McMaster Osteoarthritis Index (WOMAC) questionnaire. Radiographic knee osteophyte and joint space narrowing (JSN) were recorded. Magnetic resonance imaging (MRI) was utilized to assess popliteal cysts, subgastrocnemius bursitis, cartilage defects and bone marrow lesions (BMLs).

Results

Popliteal cysts were present in 11.7% and subgastrocnemius bursitis in 12.7% of subjects. Subgastrocnemius bursitis was more common in those with popliteal cyst (36.2% versus 9.7%, P <0.01). In multivariable analyses, popliteal cysts were significantly associated with increased osteophytes in both medial and lateral tibiofemoral compartments while subgastrocnemius bursitis was associated with increased osteophytes and JSN in the medial tibiofemoral compartment. Both were significantly associated with cartilage defects in all compartments, and with BMLs in the medial tibiofemoral compartment. Furthermore, both popliteal cysts and subgastrocnemius bursitis were significantly associated with increased weight-bearing knee pain but these associations became non-significant after adjustment for cartilage defects and BMLs.

Conclusions

Popliteal cysts and subgastrocnemius bursitis are associated with increased symptoms as well as radiographic and MRI-detected joint structural abnormalities. Longitudinal data will help resolve if they are a consequence or a cause of knee joint abnormalities.     

Diabetes screening intervals based on risk stratification

Background

Guidelines for frequency of Type 2 diabetes mellitus (DM) screening remain unclear, with proposed screening intervals typically based on expert opinion. This study aims to demonstrate that HbA1c screening intervals may differ substantially when considering individual risk for diabetes.

Methods

This was a multi-institutional retrospective open cohort study. Data were collected between April 1999 to March 2014 from one urban and one rural cohort in Japan. After categorization by age, we stratified individuals based on cardiovascular disease risk (Framingham 10-year cardiovascular risk score) and body mass index (BMI). We adapted a signal-to-noise method for distinguishing true HbA1c change from measurement error by constructing a linear random effect model to calculate signal and noise of HbA1c. Screening interval for HbA1c was defined as informative when the signal-to-noise ratio exceeded 1.

Results

Among 96,456 healthy adults, 46,284 (48.0%) were male; age (range) and mean HbA1c (SD) were 48 (30–74) years old and 5.4 (0.4)%, respectively. As risk increased among those 30–44 years old, HbA1c screening intervals for detecting Type 2 DM consistently decreased: from 10.5 (BMI <18.5) to 2.4 (BMI?>?30) years, and from 8.0 (Framingham Risk Score <10%) to 2.0 (Framingham Risk Score ≥20%) years. This trend was consistent in other age and risk groups as well; among obese 30–44 year olds, we found substantially shorter intervals compared to other groups.

Conclusion

HbA1c screening intervals for identification of DM vary substantially by risk factors. Risk stratification should be applied when deciding an optimal HbA1c screening interval in the general population to minimize overdiagnosis and overtreatment.