[Recurrent SARS-CoV-2 infections in immunodeficiency]. / Rezidivierende SARS-CoV-2-Infektionen bei Immundefizienz.

A patient with immunodeficiency due to a B-cell lymphoma has repeatedly been tested positive for SARS-CoV­2 during the ongoing SARS-CoV­2 pandemic and has twice received in-hospital treatment. Chronic and recurrent SARS-CoV­2 infections are a threat to the individual health of immunodeficient patients. Only few therapeutic options are available especially due to emerging virus variants with immune escape mechanisms. The medical care of immunodeficient patients with SARS-CoV­2 infections is a great challenge to the treating physician in the ongoing pandemic.

HIV DNA reservoir and elevated PD-1 expression of CD4 T-cell subsets particularly persist in the terminal ileum of HIV-positive patients despite cART.

OBJECTIVES: Despite its importance as an HIV anatomic sanctuary, little is known about the characteristics of the HIV reservoir in the terminal ileum (TI). In blood, the immune checkpoint inhibitor programmed-death-1 (PD-1) has been linked to the HIV reservoir and T-cell immune dysfunction. We thus evaluated PD-1 expression and cell-associated HIV DNA in memory CD4 T-cell subsets from TI, peripheral blood (PB) and rectum (RE) of untreated and treated HIV-positive patients to identify associations between PD-1 and HIV reservoir in other sites. METHODS: Using mononuclear cells from PB, TI and RE of untreated HIV-positive (N = 6), treated (n = 18) HIV-positive and uninfected individuals (n = 16), we identified and sorted distinct memory CD4 T-cell subsets by flow cytometry, quantified their cell-associated HIV DNA using quantitative PCR and assessed PD-1 expression levels using geometric mean fluorescence intensity. Combined HIV-1 RNA in situ hybridization and immunohistochemistry was performed on ileal biopsy sections. RESULTS: Combined antiretroviral therapy (cART)-treated patients with undetectable HIV RNA and significantly lower levels of HIV DNA in PB showed particularly high PD-1 expression in PB and TI, and high HIV DNA levels in TI, irrespective of clinical characteristics. By contrast, in treatment-naïve patients HIV DNA levels in memory CD4 T-cell subsets were high in PB and TI. CONCLUSION: Elevated PD-1 expression on memory CD4 T-cells in PB and TI despite treatment points to continuous immune dysfunction and underlines the importance of evaluating immunotherapy in reversing HIV latency and T-cell reconstitution. As HIV DNA particularly persists in TI despite cART, investigating samples from TI is crucial in understanding HIV immunopathogenesis.

[Modern concepts for the dynamic preservation of the liver and kidneys in the context of transplantation]. / Moderne Konzepte zur dynamischen Konservierung von Leber und Nieren im Rahmen einer Transplantation.

The increasing demand on donor grafts has forced experimental research on transplantation medicine to develop more efficient organ preservation strategies. Simple cold storage of grafts rarely offers optimal conditions for extended criteria donor organs. Hypothermic, oxygenated machine perfusion (HMP) is a classical method of dynamic organ preservation, which enables the provision of oxygen and nutrients to the tissue and provides a metabolic recovery of the graft prior to implantation. A more modern approach is normothermic machine perfusion (NMP), which instead simulates physiological conditions and enables an ex vivo evaluation and treatment of organ grafts. However, studies have found that a preceding period of cold storage significantly mitigates the functional advantage of NMP. A strategy to circumvent this phenomenon is controlled oxygenated rewarming (COR). The cold-stored graft is slowly and gradually rewarmed to subnormothermic or normothermic temperatures, providing a gentle adaption of energy metabolism and counteracting events of rewarming injury.

Performance of a recombinant fusion protein linking coagulation factor IX with recombinant albumin in one-stage clotting assays.

Essentials Performance of the one-stage clotting (OSC) assay varies with the clotting activator used. Recombinant FIX-albumin fusion protein (rIX-FP) was reliably monitored with most OSC reagents. rIX-FP shows comparable reagent-dependent variability to other rFIX products in the OSC assay. Actin® FS and kaolin-based reagents underestimated rIX-FP activity by around 50% in the OSC assay. SUMMARY: Background Measuring factor IX activity (FIX:C) with one-stage clotting (OSC) assays, based on the activated partial thromboplastin time (APTT), is the current mainstay of diagnostic techniques for hemophilia B. Assessing the performance of new recombinant FIX (rFIX) products in OSC assays is essential, as APTT reagents from different manufacturers yield different potency estimates for rFIX. Objectives To evaluate the extent to which choice of reagent composition influences rFIX potency measurements of recombinant FIX-albumin fusion protein (rIX-FP, IDELVION) activity in OSC assays. Methods rIX-FP was added to FIX-deficient plasma, and FIX:C was assessed centrally and locally in a multicenter international field study with a variety of commercial OSC APTT reagents. Paired sample analysis of clinical samples was performed to compare values of FIX:C from local and central laboratories. In-house bioanalytical investigations with spiked samples were conducted to compare the APTT-reagent dependent variability of rIX-FP with unmodified rFIX and rFIX Fc fusion protein (rFIXFc). Results Central and local assessments of FIX:C from 10 countries and 21 participating centers showed comparable results to those from the central laboratory across the majority of 18 different APTT reagents from both clinical and spiked samples. There was a consistent underestimation of rIX-FP activity of ≈ 50% with OSC assays using Actin FS or kaolin-based APTT reagents. In the bioanalytical study, rIX-FP showed comparable variability in OSC assays to unmodified rFIX and rFIXFc. Conclusions rIX-FP activity can be accurately measured by the use of OSC assays with the majority of commercial reagents. Actin FS or kaolin-based reagents will probably lead to a 50% underestimation of activity.

To prescribe, or not to prescribe: decision making in HIV-1 post-exposure prophylaxis.

OBJECTIVES: We investigated the trend in usage of post-exposure prophylaxis (PEP) after HIV-1 risk exposure and evaluated PEP prescription decision making of physicians according to guidelines. METHODS: All PEP consultations from January 2014 to December 2016 in patients presenting at the University Hospital of Cologne (Germany) were retrospectively analysed. HIV risk contacts included sexual and occupational exposure. The European AIDS Clinical Society (EACS) Guidelines for HIV PEP (version 9.0, 2017) were used for assessment. RESULTS: A total of 649 patients presented at the emergency department (ED) or the clinic for infectious diseases (IDC) for PEP consultations. A continuous increase in the number of PEP requests was recorded: 189 in 2014, 208 in 2015 and 252 in 2016. PEP consultations in men who have sex with men (MSM) showed a remarkable increase in 2016 (2014, n = 96; 2015, n = 101; 2016, n = 152). Decisions taken by physicians with a specialization in infectious diseases (n = 547) included 61 (11%) guideline-discordant prescriptions [2014: 14% (n = 22); 2015: 9% (n = 16); 2016: 11% (n = 23)]. Among these, sexual exposure accounted for 45 (74%) cases, including 15 cases of nonconsensual sex, while occupational exposure accounted for 14 (23%) cases and other exposure two cases (3%). The main reason for guideline-discordant PEP prescriptions was emotional stress of the patient (n = 37/61). CONCLUSIONS: PEP prescriptions are increasing and decision making is influenced by patients' emotional stress, but PEP prescriptions should be strictly administered according to risk assessment.

International comparative field study evaluating the assay performance of AFSTYLA in plasma samples at clinical hemostasis laboratories.

Essentials AFSTYLA exhibits ≈50% underestimation in activity when the one-stage (OS) assay is utilized. A field study compared the performance of AFSTYLA with Advate in factor VIII activity assays. AFSTYLA activity can be monitored with both the chromogenic substrate and the OS assay. The consistent OS underestimation allows for a conversion factor to be applied to OS results. SUMMARY: Introduction AFSTYLA (antihemophilic factor [recombinant] single chain) is a novel B-domain truncated recombinant factor VIII (rFVIII). For AFSTYLA, an approximate 50% discrepancy was observed between results of the one-stage (OS) and chromogenic substrate (ChS) FVIII activity assays. An investigation was undertaken to test whether there is a linear relationship between ChS and OS assay results that would allow reliable clinical interpretation of results independent of the assay method used. Aims To provide confidence in future clinical monitoring, this field study investigated the performance of AFSTYLA and a full-length rFVIII (Advate® ) in FVIII activity assays routinely performed in clinical laboratories. Methods The comparison of AFSTYLA and Advate was performed in an international, multicenter and blinded field study of simulated post-infusion samples. The study documented the extent of variability between methods and laboratories and characterized the relationship between the ChS and OS assays. Results Results from 23 laboratories demonstrate that intra and interlaboratory variability in OS assays were similar for both products. When comparing within the OS assay format, there was a similar and reagent-correlated variability in response to different activators for both AFSTYLA and Advate. The OS underestimation was highly predictable and consistent across the complete range of FVIII plasma concentrations. Conclusion Post-infusion plasma AFSTYLA levels can be monitored in patients by the OS and ChS assays. The consistent and predictable difference between the two assay formats provides clinicians with adequate guidance on how to interpret the results of the OS assay using a single conversion factor.

Impact of electrical stimulation of the stomach on gastric distension-induced emesis in the musk shrew.

BACKGROUND: Gastric electrical stimulation (GES) is implicated as a potential therapy for difficult-to-treat nausea and vomiting; however, there is a lack of insight into the mechanisms responsible for these effects. This study tested the relationship between acute GES and emesis in musk shrews, an established emetic model system. METHODS: Urethane-anesthetized shrews were used to record emetic responses (monitoring intra-tracheal pressure and esophageal contractions), respiration rate, heart rate variability, blood pressure, and gastrointestinal electromyograms. We investigated the effects of acute GES pulse duration (0.3, 1, 5, and 10 ms), current amplitude (0.5, 1, and 2 mA), pulse frequency (8, 15, 30, and 60 Hz), and electrode placement (antrum, body, and fundus) on emesis induced by gastric stretch, using a balloon. KEY RESULTS: There were four outcomes: (i) GES did not modify the effects of gastric stretch-induced emesis; (ii) GES produced emesis, depending on the stimulation parameters, but was less effective than gastric stretch; (iii) other physiological changes were closely associated with emesis and could be related to a sub-threshold activation of the emetic system, including suppression of breathing and rise in blood pressure; and (iv) a control experiment showed that 8-OH-DPAT, a reported 5-HT1A receptor agonist that acts centrally as an antiemetic, blocked gastric stretch-induced emesis. CONCLUSIONS AND INFERENCES: These results do not support an antiemetic effect of acute GES on gastric distension-induced emesis within the range of conditions tested, but further evaluation should focus on a broader range of emetic stimuli and GES stimulation parameters.

Near-infrared excited ultraviolet emitting upconverting phosphors as an internal light source in dry chemistry test strips for glucose sensing.

Upconverting phosphors are inorganic crystals with interesting optical properties, including the ability to convert infrared radiation to emission at shorter wavelengths. In this paper we present the utilization of nanosized ß-NaYF4:Yb(3+),Tm(3+), synthesized in the presence of K(+), emitting at 365 nm under 980 nm excitation as an internal light source in glucose sensing dry chemistry test strips. The feasibility of the nanoparticles as an internal UV light source was compared to the use of an external broadband lamp. The results obtained from glucose measurements using UCNPs were in agreement with the traditional method based on measuring reflectance using an external UV light source. In addition the multiple emission peaks of UCNPs offered the possibility of using them as a control signal to account for various sources of error arising in the assay. The high penetration depth of the NIR-excitation made it also possible to excite the UCNPs through a layer of whole blood, giving more freedom to the design of the optical setup.

Requirement of MyD88 and Fas pathways for the efficacy of allergen-free immunotherapy.

BACKGROUND: We have shown that mycobacterial antigens and CpG oligodeoxynucleotides downmodulate airway allergic inflammation by mechanisms dependent on T-cell activation. Here, we investigated the participation of the innate response, particularly the role of MyD88 adaptor, and Fas molecules in the effectiveness of DNA-HSP65 or CpG/culture filtrated proteins (CFP) immunotherapy. METHODS: Mice sensitized and challenged with Der p 1 allergen were treated with DNA-HSP65, CpG/CFP, or with adoptively transferred cells from immunized mice. The treatment efficacy was assessed by evaluating eosinophil recruitment, antibody, and cytokine production. RESULTS: In addition to downregulating the Th2 response, DNA-HSP65 and CpG/CFP promoted IL-10 and IFN-γ production. Adoptive transfer of cells from mice immunized with DNA-HSP65 or CpG/CFP to allergic recipients downmodulated the allergic response. Notably, transfer of cells from DNA-HSP65- or CpG/CFP-immunized MyD88(-/-) mice failed to reduce allergy. Additionally, for effective reduction of allergy by cells from CpG/CFP-immunized mice, Fas molecules were required. Although DNA-HSP65 or CpG/CFP immunization stimulated antigen-specific production of IFN-γ and IL-10, the effect of DNA-HSP65 was associated with IL-10 while CpG/CFP was associated with IFN-γ. Moreover, after stimulation with mycobacterial antigens plus Der p 1 allergen, cells from mite-allergic patients with asthma exhibited similar patterns of cytokine production as those found in the lung of treated mice. CONCLUSIONS: This study provides new insights on the mechanisms of allergen-free immunotherapy by showing that both DNA-HSP65 and CpG/CFP downregulated house dust mite-induced allergic airway inflammation via distinct pathways that involve not only induction of mycobacterial-specific adaptive responses but also signaling via MyD88 and Fas molecules.

[Blood transfusions: risks beyond communicable diseases]. / Bluttransfusionen: Risiken jenseits von übertragbaren Krankheiten.

Blood transfusions are daily practice in orthopaedic surgery and traumatology. Due to new surgical techniques and a better understanding of anaemia-associated pathophysiology, the indications for transfusion are becoming more and more strict. This is even more important as in the past few years increasing evidence shows that blood transfusions have a significant impact on hospital mortality and the patient's outcome. This article is intended to provide an overview of the literature in recent years dealing with this problem.

Combination of interfragmentary screws and locking plates in distal meta-diaphyseal fractures of the tibia: a retrospective, single-centre pilot study.

UNLABELLED: If distal tibia fractures cannot be treated with intramedullary nails, locking compression plates, such as the LCP Medial Distal Tibia Plate of Synthes, are used. Bridge plating with interfragmentary movement is the strategy for such osteosynthesis. Interfragmentary movement is difficult to predict. Too much movement leads to formation of more, but less stable callus; longer time until complete fracture healing has been reported. Interfragmentary movement can be controlled by the stability and flexibility of the osteosynthesis construct. We used interfragmentary screws to limit interfragmentary movement in certain cases. We noticed a tendency of faster fracture healing in patients with interfragment lag screw compared with those with sole bridge plating. We therefore retrospectively assessed our patients for time until clinical fracture healing (i.e., pain-free weight bearing and visible callus in both layers on conventional plain film radiographs) and callus formation. METHODS: Data (from patient chart and from regular visits) of 52 patients with fracture of the distal tibia were reviewed, of which 11 were lost to follow-up. After surgery, weight bearing was limited to 20 kg for 6 weeks and then increased in weekly intervals to the pain threshold. X-rays were taken after 3 days, 6, 12 and 24 weeks and when achieving full weight bearing. Time from surgery until ability to full weight bearing was measured and compared. Callus index was measured as quotient of callus thickness and diameter of corticalis both in a.p. and sagittal direction. Statistical evaluation was done with the Mann-Whitney U-test. RESULTS: A total of 41 patients could be analysed; of them, 30 patients had extra-articular fractures. Four patients had 43-B and seven patients had 43-C fractures. As many as 13/30 extra-articular fractures were treated with interfragmentary screws: In this group (n=11, without considering one patient with plate failure and one with pseudarthrosis) time to full weight bearing was 11.38 weeks versus 14.9 weeks without screw (n=14; without two pseudarthrosis and one deep infection) (p=0.044). Callus index at full weight bearing was significantly lesser in patients with screw compared with those without. CONCLUSION: Though interfragmentary screws seem to block necessary interfragmentary movement, we see callus formation as a sign of secondary fracture healing. The osteosynthesis construct with interfragmentary screw seems to be more stable and less flexible than sole bridge plating, leading to faster fracture healing. Interfragmentary screws might help to control and limit interfragmentary movement in certain cases.

Rumen pH and fermentation characteristics in dairy cows supplemented with Megasphaera elsdenii NCIMB 41125 in early lactation.

This study investigated the effect of using the lactate-utilizing bacterium Megasphaera elsdenii NCIMB 41125 as a probiotic supplement on rumen fermentation and pH in dairy cows in the immediate postcalving period. Fourteen multiparous rumen-fistulated Holstein cows, blocked according to 305-d milk yield in the previous lactation, were used in a randomized complete block design. From d 1 to 28 postcalving, cows were fed ad libitum a total mixed ration with a forage to concentrate ratio of 392:608 and a starch concentration of 299g/kg of dry matter. Treatments consisting of a minimum of 10(10) cfu of Megasphaera elsdenii NCIMB 41125 or autoclaved M. elsdenii (placebo) were administered via the rumen cannula on d 3 and 12 of lactation (n=7 per treatment). Mid-rumen pH was measured every 15min, and eating and ruminating behaviors were recorded for 24h on d 2, 4, 6, 8, 11, 13, 15, 17, 22, and 28. Rumen fluid for volatile fatty acid and lactic acid analysis was collected at 11 time points on each of d 2, 4, 6, 13, and 15. Yields of milk and milk protein and lactose were similar, but milk fat concentration tended to be higher in cows that received the placebo. Time spent eating and ruminating and dry matter intake were similar across treatments. Ruminal lactic acid concentrations were highly variable between animals, and no cases of clinical acidosis were observed. Both treatment groups had rumen pH <5.6 for more than 3h/d (a commonly used threshold to define subacute ruminal acidosis), but the length of time with rumen pH <5.6 was markedly reduced in the days immediately after dosing and fluctuated much less from day to day in cows that received M. elsdenii compared with those that received the placebo. Ruminal total volatile fatty acid concentrations were similar across treatments, but the acetate:propionate ratio tended to be smaller in cows that received M. elsdenii. Despite the lack of a measurable treatment effect on ruminal lactic acid concentration, supplementation of early lactation dairy cows with lactate-utilizing M. elsdenii altered the rumen fermentation patterns in favor of propionate, with potential benefits for energy balance and animal productivity.

[Antibiotic prophylaxis in primary and revision hip arthroplasty: what is the evidence?]. / Antibiotische Infektionsprophylaxe in der Primär- und Revisionsendoprothetik der Hüfte: Was ist erwiesen?

Advances in the perioperative and postoperative management of total joint replacement have led to a steady decrease in the infection rate, which in the case of total hip replacement presently lies between 0.25 and 1%. Unfortunately there is disparity in current practice nationally and internationally, regarding duration, time of application and choice of antibiotics. Currently there are only Level 1a recommendations for primary hip arthroplasty, whereas, due to the heterogeneity and complexity of most revision cases as well as a lack of randomized controlled trials, antibiotic prophylaxis for hip revision arthroplasty is mostly based on the surgeon's preference. In this article the current literature is reviewed and scientifically sound data and recommendations are summarized.

Signal transduction via cannabinoid receptors.

The endocannabinoids anandamide and 2-arachidonoylglycerol are lipid mediators that signal via CB(1) and CB(2) cannabinoid receptors and Gi/o-proteins to inhibit adenylyl cyclase and stimulate mitogen-activated protein kinase. In the brain, CB(1) receptors interact with opioid receptors in close proximity, and these receptors may share G-proteins and effector systems. In the striatum, CB(1) receptors function in coordination with D(1) and D(2) dopamine receptors, and combined stimulation of CB(1)-D(2) receptor heteromeric complexes promotes a unique interaction to stimulate cAMP production. CB(1) receptors also trigger growth factor receptor signaling cascades in cells by engaging in cross-talk or interreceptor signal transmission with the receptor tyrosine kinase (RTK) family. Mechanisms for CB(1) receptor-RTK transactivation can include stimulation of signal transduction pathways regulated by second messengers such as phospholipase C, metalloprotease cleavage of membrane-bound precursor proteins such as epidermal growth factor which activate RTKs, RTK autophosphorylation, and recruitment of non-receptor tyrosine kinases. CB(1) and CB(2) receptors are expressed in peripheral tissues including liver and adipose tissue, and are induced in pathological conditions. Novel signal transduction resulting from endocannabinoid regulation of AMP-regulated kinase and peroxisome proliferator-activated receptors have been discovered from studies of hepatocytes and adipocytes. It can be predicted that drug discovery of the future will be based upon these novel signal transduction mechanisms for endocannabinoid mediators.

Chemokine CXCL13 is overexpressed in the tumour tissue and in the peripheral blood of breast cancer patients.

The abilities of chemokines in orchestrating cellular migration are utilised by different (patho-)biological networks including malignancies. However, except for CXCR4/CXCL12, little is known about the relation between tumour-related chemokine expression and the development and progression of solid tumours like breast cancer. In this study, microarray analyses revealed the overexpression of chemokine CXCL13 in breast cancer specimens. This finding was confirmed by real-time polymerase chain reaction in a larger set of samples (n = 34) and cell lines, and was validated on the protein level performing Western blot, ELISA, and immunohistochemistry. Levels of CXCR5, the receptor for CXCL13, were low in malignant and healthy breast tissues, and surface expression was not detected in vitro. However, we observed a strong (P = 0.0004) correlation between the expressions of CXCL13 and CXCR5 in breast cancer tissues, indicating a biologically relevant role of CXCR5 in vivo. Finally, we detected significantly elevated serum concentrations of CXCL13 in patients with metastatic disease (n = 54) as compared with controls (n = 44) and disease-free patients (n = 48). In conclusion, CXCL13 is overexpressed within breast cancer tissues, and increased serum levels of this cytokine can be found in breast cancer patients with metastatic disease pointing to a role of CXCL13 in the progression of breast cancer, suggesting that CXCL13 might serve as a useful therapeutic target and/or diagnostic marker in this malignancy.

Auditory-motor coupling of bilateral finger tapping in children with and without DCD compared to adults.

The ability to modulate bilateral finger tapping in time to different frequencies of an auditory beat was studied. Twenty children, 7 years of age, 10 with and 10 without developmental coordination disorder (DCD), and 10 adults tapped their left index and right middle fingers in an alternating pattern in time with an auditory signal for 15s (four trials each, randomly, at 0.8, 1.6, 2.4, 3.2 Hz per finger). Dominant and non-dominant finger data were collapsed since no differences emerged. All three groups were able to modulate their finger frequency across trials to closely approximate the signal frequency but children with DCD were unable to slow down to the lowest frequency. Children with DCD were more variable in tap accuracy (SD of relative phase) and between finger coordination than typically developing children who were respectively more variable than the adults. Children with DCD were unable to consistently synchronize their finger with the beat. Adults were tightly synchronized and often ahead of the beat while children without DCD tended to be behind the beat. Overall, these results indicated that children with DCD can only broadly match their finger movements to an auditory signal with variability and poor synchronicity as key features of their auditory-fine-motor control. Individual inspection of the data revealed that five children with DCD had difficulty matching the slowest frequencies and that these children also had higher variability and lower percentile MABC scores from the movement assessment battery for children (MABC) than other children with DCD. Three children with DCD were more variable only at higher frequencies and two performed like typically developing children.

SOCS in situ expression in tuberculous lymphadenitis in an endemic area.

BACKGROUND: The immune response to Mycobacterium tuberculosis is complex and multifactorial, the cytokine system being a major factor in M. tuberculosis immunity. AIM: To analyze the immunohistochemical aspects of tuberculous lymph nodes in immunocompetent patients and search for associations between SOCS and cytokine expression in human tuberculous lymphadenitis. METHODS: Thirteen lymph nodes were assayed by immunohistochemistry for SOCS-1 and 3, STAT-3, RANTES, MIP-1-alpha, ICAM-1, IFN-gamma as well as CD45RO, CD20, CD34, CD68, trypsin and lysozyme. Additionally, the RT in situ PCR was performed for SOCS-1 and 3 mRNA detection. RESULTS: Decreased MIP-1 alpha expression together with reduced SOCS-3 (p=0.042), lysozyme (p=0.024) and CD45RO (p=0.05) was observed in the TB lymph nodes compared to the control lymph nodes. In conclusion, the lymphadenitis due to M. tuberculosis was associated with a downregulation of memory T cells (CD45RO), activated lysozymes and SOCS-3 compared to controls, which may play a role in the long-term bacterial replication and altered immune modulation characteristic of the disease.

[Peripheral arterial disease: predictors and treatment intensity. Two-years of data from the population-based INVADE project]. / Periphere arterielle Verschlusskrankheit: Prädiktoren und Behandlungsintensität. 2-Jahres Daten des populationsbasierten INVADE-Projekts

BACKGROUND AND PURPOSE: Asymptomatic peripheral arterial disease (PAD) is very common in the elderly and can be detected in 15-20% of patients above 55 years. The aim of this study was to determine PAD prevalence and risk factors within the population of the overall INVADE project (INtervention project of cerebroVAscular diseases and Dementia in the District of Ebersberg [Bavaria]), a prospective non-randomized analysis. PATIENTS AND METHODS: A total of 3,909 participants were included in the INVADE project. An ankle-brachial index (ABI) measurement was available in 3 891 subjects. An additional 40 patients were excluded because their ABI was >1,5. The analysis was thus based on 3,851 participants. The mean age was 70.1 years (95% confidence interval: 69,8 - 70,3). There were 2 285 (59.3%) women. The changes of the different classical vascular and risk factors as well as various laboratory parameters, including high sensitivity C-reactive protein (hs-CRP) were recorded and analysed by the paired t-test or the Fisher's exact test. Independent predictors were calculated by multiple logistic regression analysis. RESULTS: The prevalence of PDA was 18.6%. In 75% of the PAD patients the diagnosis had been unknown before study onset. Those with PAD were significant younger (69.6 vs. 72.2 years; p<0.0001), had significant lower hsCRP values (3,8 mg/l vs. 4.9 mg/l; p=0.002) and a lower vascular risk profile. After two years of intervention an improvement of vascular risk factors and reduction in necessary treatment, such as antihypertensives and platelet inhibitors, was documented. Independent risk factors for PAD development, in addition to the baseline ABI, were age, years of smoking (packs per day) and hsCRP. CONCLUSION: The INVADE project confirms the high prevalence of PAD in an elderly population. These data underline the importance of measuring hsCRP for diagnosing and following PAD development.

[Modification of vascular risk factors by intervention on the primary care level. Results of the INVADE project]. / Modifikation vaskulärer Risikofaktoren durch hausärztliche Intervention. Ergebnisse des Projekts INVADE.

BACKGROUND: The so-called INVADE project examines the efficacy of consistent diagnosis and treatment of cerebrovascular risk factors on the incidence of stroke. METHODS: This analysis compares known cardiovascular risk factors (elevated blood pressure, dipositas, hyperlipidemia, diabetes mellitus, and smoking) and respective medication of 2930 patients with respect to cerebrovascular disease, peripheral arterial disease (PAD), and coronary heart disease (CHD) between baseline and follow-up examination after 2 years of intervention. RESULTS: Using the ankle-brachial index (ABI), 381 patients (13%) with asymptomatic PAD were identified. Comparison between baseline and follow-up examination revealed significant reductions in the following risk factors. Cerebrovascular disease: elevated blood pressure -12.8%, dipositas -4.2%, and LDL -8.1%. For PAD the results were: elevated blood pressure -7.2%, smoking -1.2%, elevated cholesterol -6.4%, dipositas -3.2%, and LDL -7.4%. For CHD the results were: elevated blood pressure -11.3%, elevated cholesterol -13.0%, and LDL -14.9%. CONCLUSION: By the use of ABI, previously undiagnosed asymptomatic PAD was identified in 13% of all patients. Two-year intervention on the primary care level yielded significant reduction of known vascular risk factors.