Nuclear imaging to visualize periodontal inflammation: Findings of a randomized controlled trial.

OBJECTIVE: To investigate non-surgical periodontal therapy by 18F-fluorodeoxyglucose (2-[18 F]FDG) uptake using positron emission tomography (PET) integrated with computed tomography (CT). SUBJECTS: Eighty-five patients with peripheral artery disease and severe periodontitis-randomized into three groups receiving therapy with (PT1; n = 29) or without (PT2; n = 28) systemic antibiotics or no treatment (controls: n = 28)-underwent nuclear imaging at baseline and at 3 months. RESULTS: Clinical inflammation (periodontal inflamed surface area; PISA) did not significantly differ across the groups at baseline (p = 0.395) but was significantly reduced at 3 months (p < 0.001), and significantly more so in the PT1/PT2 groups than in the control group (p < 0.001/=0.025) and in the PT1 than in the P2 group (p = 0.001). Radiotracer uptake was measured in both jaws using maximum and mean 'standardized uptake values' (SUVmax , SUVmean ) and 'target-to-background ratios' (TBRmax , TBRmean ). At 3 months, reductions were relatively small in absolute numbers and fell short of revealing correlations with PISA or significant differences across the groups. Still, they were very consistent in both treatment groups, whereas reductions were not consistently seen in the control group. CONCLUSIONS: 2-[18 F]FDG PET/CT scans did reflect the clinical effects of periodontal treatment very consistently but, for reasons yet to be clarified, less closely than expected.

Usability of a telehealth-nurse supported home-based walking training for peripheral arterial disease - The Keep Pace! pilot study.

Background: Guidelines recommend walking trainings for peripheral arterial disease (PAD) management. Supervised walking training is superior to walking advise to improve the walking distance. Telehealth service with nurse support may close this gap. Patients and methods: This study introduces a telehealth service, "Keep pace!", which has been developed for patients with symptomatic PAD (Fontaine stage IIa and IIb), enabling a structured home-based walking training while monitoring progress via an app collecting unblinded account of steps and walking distance in self-paced 6-minute-walking-tests by geolocation tracking to enhance intrinsic motivation. Supervision by nurses via telephone calls was provided for 8 weeks, followed by 4 weeks of independent walking training. Patient satisfaction, walking distance and health-related quality of life were assessed. Results: 19 patients completed the study. The analysis revealed an overall high satisfaction with the telehealth service (95.4%), including system quality (95.1%), information quality (94.4%), service quality (95.6%), intention to use (92.8%), general satisfaction with the program (98.4%) and health benefits (95.8%). 78.9% asserted that the telehealth service lacking nurse calls would be less efficacious. Pain-free walking distance (76.3±36.8m to 188.4±81.2m, +112.2%, p<0.001) as well as total distance in 6-minute-walking test (308.8±82.6m to 425.9±107.1m, +117.2%, p<0.001) improved significantly. The telehealth service significantly reduced discomfort by better pain control (+15.5%, p=0.015) and social participation (+10.5%, p=0.042). Conclusions: In conclusion, patients were highly satisfied with the telehealth service. The physical well-being of the PAD patients improved significantly post vs. prior the telehealth program.

Dietary intake in patients with peripheral arterial disease and concomitant periodontal disease.

Nutrition plays a crucial role in the pathophysiology and management of peripheral arterial disease (PAD) and periodontal disease (PD). As PD can have profound effects on an individual's functional ability to eat and can affect nutrient intake, we aimed to evaluate the role of PD severity on dietary intake (DI) and quality in PAD patients and compare it with current dietary recommendations for CVD. PD stages of 421 consecutive PAD patients were determined according to a standardised basic periodontal examination (Periodontal Screening and Recording Index) ('healthy', 'gingivitis', 'moderate periodontitis' and 'severe periodontitis'). Dietary intake (24-h recall), dietary quality (food frequency index (FFI)) and anthropometrical data were assessed. Nutritional intake was stratified according to the severity of PD. No significant differences in DI of macronutrients, nutrients relevant for CVD and FFI were seen between the PD stages. Only median alcohol intake was significantly different between gingivitis and severe periodontitis (P = 0·001), and positively correlated with PD severity (P = 0·001; r 0·159). PD severity and the patient's number of teeth showed no correlation with investigated nutritional parameters and FFI. Few subjects met the recommended daily intakes for fibre (5 %), SFA (10 %), Na (40 %) and sugar (26 %). Macronutrient intake differed from reference values. In our sample of patients with PAD and concomitant PD, we found no differences in DI of macronutrients, nutrients relevant for CVD and diet quality depending on PD severity. The patients' nutrition was, however, poor, deviating seriously from dietary guidelines and recommendations.

Age-dependent effects of homocysteine and dimethylarginines on cardiovascular mortality in claudicant patients with lower extremity arterial disease.

The association among serum homocysteine (HCY), symmetric dimethylarginine (SDMA), and asymmetric dimethylarginine (ADMA) is of interest in endothelial dysfunction, although the underlying pathology is not fully elucidated. We investigated the relationship of HCY with SDMA and ADMA regarding their long-time outcome and the age dependency of HCY, SDMA, and ADMA values in claudicant patients with lower extremity arterial disease. 120 patients were included in a prospective observational study (observation time 7.96 ± 1.3 years) with cardiovascular mortality as the main outcome parameter. Patients with intermittent claudication prior to their first endovascular procedure were included. HCY, SDMA, and ADMA were measured by high-performance liquid chromatography. Cutoff values for HCY (≤/>15 µmol/l), SDMA (≤/>0.75 µmol/l), and ADMA (≤/>0.8 µmol/l) differed significantly regarding cardiovascular mortality (p < 0.001, p < 0.001, p = 0.017, respectively). Age correlated significantly with HCY (r = 0.393; p < 0.001), SDMA (r = 0.363; p < 0.001), and ADMA (r = 0.210; p = 0.021). HCY and SDMA (r = 0.295; p = 0.001) as well as SDMA and ADMA (r = 0.380; p < 0.001) correlated with each other, while HCY and ADMA did not correlate (r = 0.139; p = 0.130). Patients older than 65 years had higher values of HCY (p < 0.001) and SDMA (p = 0.01), but not of ADMA (p = 0.133). In multivariable linear regression, age was the only significant independent risk factor for cardiovascular death (beta coefficient 0.413; 95% CI 0.007-0.028; p = 0.001). Age correlated significantly with HCY, SDMA, and ADMA. However, only age was an independent predictor for cardiovascular death. Older patients have higher values of HCY and SDMA than younger subjects suggesting age-adjusted cutoff values of HCY and SDMA due to strong age dependency.

Auricular vagal nerve stimulation in peripheral arterial disease patients.

BACKGROUND: Auricular nerve stimulation has been proven effective in different diseases. We investigated if a conservative therapeutic alternative for claudication in peripheral arterial occlusive disease (PAD) via electroacupuncture of the outer ear can be established. PATIENTS AND METHODS: In this prospective, double-blinded trial an ear acupuncture using an electroacupuncture device was carried out in 40 PAD patients in Fontaine stage IIb. Twenty patients were randomized to the verum group using a fully functional electroacupuncture device, the other 20 patients received a sham device (control group). Per patient, eight cycles (1 cycle = 1 week) of electroacupuncture were performed. The primary endpoint was defined as a significantly more frequent doubling of the absolute walking distance after eight cycles in the verum group compared to controls in a standardized treadmill testing. Secondary endpoints were a significant improvement of the total score of the Walking Impairment Questionnaire (WIQ) as well as improvements in health related quality of life using the Short Form 36 Health Survey (SF-36). RESULTS: There were no differences in baseline characteristics between the two groups. The initial walking distance significantly increased in both groups (verum group [means]: 182 [95 % CI 128-236] meters to 345 [95 % CI 227-463] meters [+ 90 %], p < 0.01; control group [means]: 159 [95 % CI 109-210] meters to 268 [95 % CI 182-366] meters [+ 69 %], p = 0.01). Twelve patients (60 %) in the verum group and five patients (25 %) in controls reached the primary endpoint of doubling walking distance (p = 0.05). The total score of WIQ significantly improved in the verum group (+ 22 %, p = 0.01) but not in controls (+ 8 %, p = 0.56). SF-36 showed significantly improvements in six out of eight categories in the verum group and only in one of eight in controls. CONCLUSIONS: Electroacupuncture of the outer ear seems to be an easy-to-use therapeutic option in an age of increasingly invasive and mechanically complex treatments for PAD patients.

Effectiveness of multi-professional educational interventions to train Comprehensive Geriatric Assessment (CGA) - a Systematic Review.

Introduction: As the world population ages, health and social care professionals are increasingly confronted with patients with chronic long-term conditions and multimorbidity, requiring an extensive assessment and integrated care management strategy. The aim of this paper was to systematically collect and assess evidence of interprofessional education and training strategies for Comprehensive Geriatric Assessment (CGA) to build a competent health workforce. Methods: A systematic review was conducted according to PRISMA guidelines and the databases Medline, CINAHL, Cochrane and Embase were searched for studies illustrating effectiveness of educational interventions for teaching and training CGA in an interprofessional context. Results: Based on 21 identified studies, a great variability and heterogeneity in duration, setting and design of the interventions was identified. Promising results were found in the domains analysed, ranging from knowledge and skills; practices and behaviour; patient health outcomes; attitudes and perceptions to collaboration and quality of care. Discussion: Education and training of transversal skills within a continuous learning approach is key to equip the health care workforce for successful CGA performance in an interprofessional environment. Conclusion: Further research in this field is recommended to strengthen the evidence-base towards development of a resilient and integrated health care workforce for an ageing population.

Lower Lean Mass Is Associated with Greater Arterial Stiffness in Patients with Lower Extremity Artery Disease.

BACKGROUND: Arterial stiffness is independently associated with lower extremity artery disease (LEAD). Although obesity is already known as an independent cardiovascular risk factor, it was found that, paradoxically, in patients diagnosed with cardiovascular disease, an increase in body mass index (BMI) was associated with a decrease in mortality. However, the underlying mechanism of this paradoxical association remain uncertain. In this study, we firstly hypothesize that arterial stiffness correlates with body mass; secondly, the underlying mechanism of the association for patients with LEAD is individual body composition, in particular, lean mass. METHODS: The present study was performed as a single-center, prospective, observational analysis. A total of 412 patients with current or previously diagnosed LEAD (Rutherford Classification 2-4) were included, the cfPWV and AIx were measured as indices of arterial stiffness, and a body composition assessment was performed. RESULTS: In male patients, there was a significantly negative correlation between the AIx and lean mass coefficient (p = 0.004, 95% CI: -0.28 (-0.48-0.09)). CONCLUSION: For patients with peripheral arterial disease, our data show that lower lean mass in male patients is associated with increased arterial stiffness as measured by the AIx. Therefore, progressive resistance training may be beneficial for the reduction in arterial stiffness in PAD patients in secondary prevention.

Periodontal treatment and vascular inflammation in patients with advanced peripheral arterial disease: A randomized controlled trial.

BACKGROUND AND AIMS: Observational studies support an association between periodontitis and cardiovascular diseases. The study objective was to assess vascular inflammation after periodontal treatment in patients with peripheral arterial disease. METHODS: Ninety patients with peripheral arterial disease (PAD) and severe periodontitis were enrolled in a randomized, controlled trial. Thirty patients underwent non-surgical periodontal therapy and received additional systemic antibiotics (PT1 group), while 30 patients received the same therapy without antibiotics (PT2 group). The remaining thirty patients did not receive periodontal therapy (CG, control group). The primary outcome of this treatment was a reduction in vascular inflammation three months after periodontal treatment as determined by 18F-FDG PET/CT values. Secondary outcomes were changes in the inflamed periodontal surface area (PISA) and other periodontal parameters, changes in vascular biomarkers, and adverse cardiovascular events. RESULTS: After three months of treatment, a significant improvement in periodontal health was observed in the treatment groups. However, no difference in the primary outcome in the aorta was observed in the three study groups (median target to background ratio follow-up/baseline, PT1 1.00; 95% CI 0.97-1.10, PT2 1.00; 95% CI 0.98-1.1, CG 1.1; 95% CI 0.99-1.1, p = 0.75). No significant differences were detected in most diseased segments and active segments. In addition, no differences were observed in 18F-FDG uptake in the carotid, iliac, femoral, and popliteal arteries. No differences with regard to relative changes in vascular biomarkers were noted, and no serious cardiovascular adverse events occurred. CONCLUSIONS: Periodontal treatment was effective and safe but did not reduce vascular inflammation in patients with PAD.

Homoarginine/ADMA ratio and homoarginine/SDMA ratio as independent predictors of cardiovascular mortality and cardiovascular events in lower extremity arterial disease.

Endothelial dysfunction plays a key role in development of atherosclerosis and lower extremity arterial disease (LEAD). Homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are sensitive markers for endothelial dysfunction and independent risk factors for cardiovascular death. However, homoarginine may influence the proatherogenic effects of ADMA and SDMA suggesting homoarginine/ADMA ratio or homoarginine/SDMA ratio as further predictors for cardiovascular mortality. Therefore, we investigated the predictive value of homoarginine/ADMA ratio and homoarginine/SDMA ratio related to cardiovascular mortality and cardiovascular events in claudicant patients with LEAD. 151 patients with intermittent claudication were included in a prospective observational study (observation time 7.7 ± 2.5 years) with cardiovascular mortality as main outcome parameter and the occurrence of cardiovascular events as secondary outcome parameter. Homoarginine, ADMA and SDMA were measured by high-performance liquid chromatography at baseline. Low homoarginine/ADMA ratio and homoarginine/SDMA ratio were independently associated with higher cardiovascular mortality (HR 2.803 [95% CI 1.178-6.674], p = 0.020; HR 2.782 [95% CI 1.061-7.290], p = 0.037, respectively) and higher incidence of cardiovascular events (HR 1.938 [95% CI 1.015-3.700], p = 0.045; HR 2.397 [95% CI 1.243-4.623], p = 0.009, respectively). We observed that homoarginine/ADMA ratio and homoarginine/SDMA ratio are independent predictors for long-term cardiovascular mortality and events in claudicant patients with LEAD.

Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis.

BACKGROUND: Because epidemiological studies provide evidence that periodontal infections are associated with an increased risk of progression of cardiovascular and cerebrovascular disease, we postulated that endothelial dysfunction, a critical element in the pathogenesis of atherosclerosis, would be present in patients with periodontal disease. METHODS: We tested endothelial function in 30 patients with severe periodontitis and 31 control subjects using flow-mediated dilation (FMD) of the brachial artery. The groups were matched for age, sex, and cardiovascular risk factors. Three months after periodontal treatment, including both mechanical and pharmacological therapy, endothelial function was reassessed by brachial artery FMD. Markers of systemic inflammation were measured at baseline and at follow up. RESULTS: Flow-mediated dilation was significantly lower in patients with periodontitis than in control subjects (6.1% +/- 4.4% vs 8.5% +/- 3.4%, P = .002). Successful periodontal treatment resulted in a significant improvement in FMD (9.8% +/- 5.7%; P = .003 compared to baseline) accompanied by a significant decrease in C-reactive protein concentrations (1.1 +/- 1.9 vs 0.8 +/- 0.8 at baseline, P = .026). Endothelium-independent nitro-induced vasodilation did not differ between the study groups at baseline or after periodontal therapy. CONCLUSION: These results indicate that treatment of severe periodontitis reverses endothelial dysfunction. Whether improved endothelial function will translate into a beneficial effect on atherogenesis and cardiovascular events needs further investigation.

Two polymorphisms in the fracalkine receptor CX3CR1 are not associated with peripheral arterial disease.

OBJECTIVE: CX(3)CR1 is a novel chemokine receptor located on monocytes. Recently, two polymorphisms were linked to coronary artery disease (CAD), V249I and T280M. Carriers of at least one I-allele or one M-allele were found less frequently among patients with CAD compared to controls. The aim of the present study was to investigate the influence of these polymorphisms on the development of peripheral arterial disease (PAD). METHODS: 522 human subjects with documented PAD and 522 age and sex matched controls were genotyped by polymerase chain reaction followed by restriction digestion. RESULTS: Adjusted odds ratio (OR) of carriers of the I-allele for PAD was 1.34 (95% confidential interval (CI) from 0.86 to 2.09; P=0.19). The OR associated with the M-allele for PAD was 0.65 (95% CI from 0.41 to 1.04; P=0.07), when tested in the same regression analysis with the V249I genotypes. The genotypes were not linked to age at onset or severity of the disease. A subgroup of 137 CAD patients of whom 131 could be genotyped and who did not differ in baseline parameters from the remaining PAD patients, showed VV-genotype in 52.0%, VI in 42.7% and II in 5.3% CAD (OR associated with the I-allele for CAD: 1.29; 95% CI: 0.66-2.51; P=0.46). The distribution of the T280M genotypes was 67.1, 29.8, 3.1% (TT, TM, MM) also showing no association with CAD (OR=0.77; 95% CI 0.36-1.46; P=0.37). CONCLUSION: In this study we could not detect a difference in genotype frequencies of the V249I and T280M polymorphisms in CX(3)CR1 between PAD patients and controls. CAD concomitant with PAD was also not affected by the I- or the M-allele.

Endothelial dysfunction and brachial intima-media thickness: long term cardiovascular risk with claudication related to peripheral arterial disease: a prospective analysis.

OBJECTIVE: Endothelial dysfunction plays a key role in the development, progression, and clinical manifestation of atherosclerosis, and in symptomatic peripheral arterial disease, endothelial dysfunction and enlarged intima-media thickness might be associated with increased cardiovascular risk. Flow-mediated dilatation and serologic parameters are used to evaluate individual endothelial function. Brachial intima-media thickness, a less recognized parameter of cardiovascular risk, is independently associated with coronary artery disease. The aim of this study was to evaluate the prognostic value of ultrasound and serologic parameters of endothelial function in relation to cardiovascular mortality in peripheral arterial disease. DESIGN: monocentric, prospective cohort study. METHODS: Flow mediated dilatation and brachial intima-media thickness were assessed in 184 (124 male) patients with peripheral arterial disease (Rutherford stages 2-3). Serologic parameters of endothelial function included asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and L-homoarginine. Cardiovascular events were recorded during a follow-up of 99.1±11.1 months. Subjects who died of noncardiovascular causes were excluded from further analysis. RESULTS: Eighty-two patients (44.6%) died during follow-up after a mean duration of 49.7±28.3 months. There were 49 cardiovascular deaths (59.8%) and 33 other deaths (40.2%). Flow mediated dilatation was associated with cardiovascular death [1.17% (0.0, 4.3) vs. 4.1% (1.2, 6.4), p<0.001]. Intima-media thickness was greater in patients who succumbed to cardiovascular disease [0.37 mm (0.30, 0.41)] than in survivors [0.21 mm (0.15, 0.38), p<0.001]. Brachial intima-media thickness above 0.345 mm was most predictive of cardiovascular death, with sensitivity and specificity values of 0.714 and 0.657, respectively (p<0.001). Furthermore, ADMA levels above 0.745 µmol/l and SDMA levels above 0.825 µmol/l were significantly associated with cardiovascular death (p<0.001 and 0.030). CONCLUSION: In symptomatic peripheral arterial disease, decreased flow mediated dilatation, enlarged intima-media thickness, and elevated levels of ADMA and SDMA were associated with increased cardiovascular risk.

Neointimal hyperplasia after silverhawk atherectomy versus percutaneous transluminal angioplasty (PTA) in femoropopliteal stent reobstructions: a controlled, randomized pilot trial.

BACKGROUND: Due to intimal hyperplasia instent reobstruction in the femoropopliteal arterial segment is still an unsolved problem. Different techniques have been discussed in case of reintervention to guarantee longlasting patency rate. METHODS: We conducted a randomized, controlled, pilot trial comparing Silverhawk atherectomy with percutaneous transluminal angioplasty (PTA) in patients with a first instent reobstruction in the femoropopliteal arterial segment, to evaluate intima media thickness (IMT) within the treated segment, as a parameter of recurrence of intimal hyperplasia. RESULTS: In a total 19 patients were included: 9 patients in the atherectomy device and 10 patients in the PTA arm. IMT within the treated segment was statistically significantly elevated in all patients treated with the Silverhawk device versus the patients treated with PTA. The obvious differentiation in elevation of IMT in nonfavor for patients treated with the Silverhawk device started at month 2 (max IMT SH 0.178 mm vs. IMT PTA 0.1 mm, p = 0.001) with a spike at month 5 (max IMT SH 0.206 mm vs. IMT PTA 0.145 mm, p = 0.003) and a decline once again at month 6 (max IMT SH 0.177 mm vs. IMT PTA 0.121 mm, p = 0.02). The values for mean IMT performed the same way. CONCLUSIONS: Although Silverhawk atherectomy provides good results at first sight, in the midterm follow-up of treatment of first instent restenosis it did not perform better than PTA as it showed elevated reoccurrence of intimal media hyperplasia.

Axillary vein compression by Langer's axillary arch, an aberrant muscle bundle of the latissimus dorsi.

BACKGROUND: Axillary vein compression is an important differential diagnosis in swelling of the upper extremities besides deep venous thrombosis. CASE REPORT: We present a rare case of axillary vein compression in a 17-year-old female with intermittent swelling and pain of the left arm due to an aberrant muscle bundle of the left latissimus dorsi. After resection of this bundle, which corresponded to Langer's axillary arch, the swelling and pain on the left arm resolved completely. CONCLUSION: In symptomatic patients with axillary vein compression due to Langer's axillary arch, a resection of the muscle bundle is an effective way of treatment.

Aggravation of pre-existing atrioventricular block, Wenckebach type, provoked by application of X-ray contrast medium.

BACKGROUND: Significant bradycardia followed by cardiac arrest related to single bolus administration of X-ray contrast medium into a peripheral artery has not, to our knowledge, been described in the literature. METHODS AND RESULTS: While performing a percutaneous transluminal angioplasty of the left superficial femoral artery in a 68-year old patient with a pre-existing atrioventricular (AV) block, Wenckebach type, he developed an AV block III after a single bolus injection of intra-arterial X-ray contrast medium. CONCLUSION: We believe that application of contrast medium causes a transitory ischemia in the obstructed vessel and therefore elevation of endogenous adenosine. In the case of a previously damaged AV node this elevation of endogenous adenosine may be responsible for the development of a short period of third-degree AV block.