Noncanonical effector functions of the T-memory-like T-PLL cell are shaped by cooperative TCL1A and TCR signaling.

T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic neoplasm. Differentiation stage and immune-effector functions of the underlying tumor cell are insufficiently characterized. Constitutive activation of the T-cell leukemia 1A (TCL1A) oncogene distinguishes the (pre)leukemic cell from regular postthymic T cells. We assessed activation-response patterns of the T-PLL lymphocyte and interrogated the modulatory impact by TCL1A. Immunophenotypic and gene expression profiles revealed a unique spectrum of memory-type differentiation of T-PLL with predominant central-memory stages and frequent noncanonical patterns. Virtually all T-PLL expressed a T-cell receptor (TCR) and/or CD28-coreceptor without overrepresentation of specific TCR clonotypes. The highly activated leukemic cells also revealed losses of negative-regulatory TCR coreceptors (eg, CTLA4). TCR stimulation of T-PLL cells evoked higher-than-normal cell-cycle transition and profiles of cytokine release that resembled those of normal memory T cells. More activated phenotypes and higher TCL1A correlated with inferior clinical outcomes. TCL1A was linked to the marked resistance of T-PLL to activation- and FAS-induced cell death. Enforced TCL1A enhanced phospho-activation of TCR kinases, second-messenger generation, and JAK/STAT or NFAT transcriptional responses. This reduced the input thresholds for IL-2 secretion in a sensitizer-like fashion. Mice of TCL1A-initiated protracted T-PLL development resembled such features. When equipped with epitope-defined TCRs or chimeric antigen receptors, these Lckpr-hTCL1Atg T cells gained a leukemogenic growth advantage in scenarios of receptor stimulation. Overall, we propose a model of T-PLL pathogenesis in which TCL1A enhances TCR signals and drives the accumulation of death-resistant memory-type cells that use amplified low-level stimulatory input, and whose loss of negative coregulators additionally maintains their activated state. Treatment rationales are provided by combined interception in TCR and survival signaling.

[A several-week history of inflammatory changes in the right foot and right hand of a 57-year-old male patient]. / Seit mehreren Wochen bestehende entzündliche Veränderungen an rechtem Fuß und rechter Hand bei einem 57-jährigen Patienten.

Metastatic fat necrosis due to inflammatory or neoplastic pancreatic diseases is rare. This phenomenon is attributed to systemic effects of pancreatic enzymes. Depending on the sites of fat necrosis, a number of different diseases may be mimicked, leading to incorrect diagnosis and therapies. Many case reports describe the phenomenon of skin, joint and bone manifestations of fat necrosis under the acronym PPP (pancreatic, panniculits, polyarthritis) syndrome. The management of "autodigestion" primarily consists of treating the underlying pancreatic disease.

Development, behaviour and sensory processing in Marshall-Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes.

BACKGROUND: Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. METHODS: Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. RESULTS: Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. CONCLUSIONS: Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.

[Selection of the optimal anesthesia regimen for cesarean section]. / Wahl des Anästhesieverfahrens zur Sectio caesarea.

Approximately one third of all children in Germany are delivered by cesarean section. Depending on the individual patient's condition and the situation, the anesthesiologist has to choose between a general or a regional anesthesia regimen. The decisive factor for the selection is the obstetric urgency (decision-delivery time) after ascertainment of the indications. Furthermore, the need for postoperative analgesia varies depending on the chosen anesthesia regimen.

[Vasculitides and eosinophilic pulmonary diseases]. / Vaskulitiden und eosinophile Lungenerkrankungen.

Eosinophilic granulocytes form peripheral effector cells controlled by Th2 lymphocytes, which cause local cell, tissue, and functional disorders of infiltrated organs via the release of cytotoxic basic proteins and oxygen radicals. Diseases associated with eosinophilia include systemic and organ-related forms. The lungs are involved in eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), acute and chronic eosinophilic pneumonia, as well as in an organ manifestation in hypereosinophilic syndrome and certain parasitic diseases. In particular, the lungs are frequently affected in vasculitis of small vessels, including EGPA, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). Among these, EGPA is the most frequent pulmonary eosinophil vasculitis representative. In addition, there are various overlap syndromes in which characteristic features of EGPA can be detected in the context of other anti-neutrophil cytoplasmic antibody (ANCA-)associated vasculitides. Occasionally, non-ANCA-associated pulmonary vasculitides occur with eosinophilia (e.g., Schönlein-Henoch purpura, Kawasaki disease, drug-induced hypersensitivity, and paraneoplastic syndrome). Herein, the pulmonary vasculitides accompanying eosinophilia are presented with respect to both the lung manifestations and pulmonary eosinophilia.

[Vasculitides and eosinophilic pulmonary diseases]. / Vaskulitiden und eosinophile Lungenerkrankungen.

Eosinophilic granulocytes form peripheral effector cells controlled by Th2 lymphocytes, which cause local cell, tissue, and functional disorders of infiltrated organs via the release of cytotoxic basic proteins and oxygen radicals. Diseases associated with eosinophilia include systemic and organ-related forms. The lungs are involved in eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), acute and chronic eosinophilic pneumonia, as well as in an organ manifestation in hypereosinophilic syndrome and certain parasitic diseases. In particular, the lungs are frequently affected in vasculitis of small vessels, including EGPA, granulomatosis with polyangiitis (GPA), and microscopic polyangiitis (MPA). Among these, EGPA is the most frequent pulmonary eosinophil vasculitis representative. In addition, there are various overlap syndromes in which characteristic features of EGPA can be detected in the context of other anti-neutrophil cytoplasmic antibody (ANCA-)associated vasculitides. Occasionally, non-ANCA-associated pulmonary vasculitides occur with eosinophilia (e.g., Schönlein-Henoch purpura, Kawasaki disease, drug-induced hypersensitivity, and paraneoplastic syndrome). Herein, the pulmonary vasculitides accompanying eosinophilia are presented with respect to both the lung manifestations and pulmonary eosinophilia.

[Validation of the German Version of the Sunnybrook Facial Grading System]. / Validierung einer Deutschen Version des Sunnybrook Facial Grading Systems.

Background: The Sunnybrook facial grading system (SFGS) is frequently applied to evaluate facial function in patients with facial palsy, but still now there is no validated German version of this evaluation sheet. Methods: The original English version of the SFGS was translated and validated in accordance with international standards. The interrater reliability from 5 raters (speech therapy students) and the intrarater reliability from repeated ratings at 2 time points using video tapes of 18 patients with different types of facial palsy were analyzed by calculating the intraclass correlation coefficient (ICC) and other reliability measures. Results: ICC for the interrater reliability for the 4 components of the SFGS, resting symmetry, symmetry during voluntary movements, synkinesis, and the composite score were ICC 0.845; 0.903; 0.731 and 0.918, respectively, for the first evaluation and ICC 0.881; 0.932; 0.818 and 0.940, respectively, for the second evaluation. The mean intrarater reliability for the 4 SFGS scores was ICC=0.791; 0.906; 0.770 and 0.905. Discussion: There is now a valid German version of the SFGS available that can be used even by novices. The German version is suitable for evaluation of facial palsies in clinical routine and studies to allow a better comparability of German patients with results of the international literature.

Trabecular bone score in type 1 diabetes--a cross-sectional study.

UNLABELLED: Trabecular bone score (TBS) seems to provide additive value on BMD to identify individuals with prevalent fractures in T1D. TBS did not significantly differ between T1D patients and healthy controls, but TBS and HbA1c were independently associated with prevalent fractures in T1D. A TBS cutoff <1.42 reflected prevalent fractures with 91.7 % sensitivity and 43.2 % specificity. INTRODUCTION: Type 1 diabetes (T1D) increases the risk of osteoporotic fractures. TBS was recently proposed as an indirect measure of bone microarchitecture. This study aimed at investigating the TBS in T1D patients and healthy controls. Associations with prevalent fractures were tested. METHODS: One hundred nineteen T1D patients (59 males, 60 premenopausal females; mean age 43.4 ± 8.9 years) and 68 healthy controls matched for gender, age, and body mass index (BMI) were analyzed. The TBS was calculated in the lumbar region, based on two-dimensional (2D) projections of DXA assessments. RESULTS: TBS was 1.357 ± 0.129 in T1D patients and 1.389 ± 0.085 in controls (p = 0.075). T1D patients with prevalent fractures (n = 24) had a significantly lower TBS than T1D patients without fractures (1.309 ± 0.125 versus 1.370 ± 0.127, p = 0.04). The presence of fractures in T1D was associated with lower TBS (odds ratio = 0.024, 95 % confidence interval (CI) = 0.001-0.875; p = 0.042) but not with age or BMI. TBS and HbA1c were independently associated with fractures. The area-under-the curve (AUC) of TBS was similar to that of total hip BMD in discriminating T1D patients with or without prevalent fractures. In this set-up, a TBS cutoff <1.42 discriminated the presence of fractures with a sensitivity of 91.7 % and a specificity of 43.2 %. CONCLUSIONS: TBS values are lower in T1D patients with prevalent fractures, suggesting an alteration of bone strength in this subgroup of patients. Reliable TBS cutoffs for the prediction of fracture risk in T1D need to be determined in larger prospective studies.

Local anesthetic toxicity: Who is ready for lipid resuscitation? A survey of German Hospitals.

PURPOSE: Toxic reactions to local anesthetics are rare but potentially lethal. In fact, animal studies and case reports demonstrate that the administration of lipid emulsions after initializing cardiopulmonary resuscitation is a promising treatment option. The aim of this study was to determine how many hospitals in Germany are prepared to treat toxic reactions to local anesthetics with lipid infusion and to identify how often and what type of toxic reactions occur and if treatment was successful. Further, we aimed to elucidate if current guidelines lead to more immediate availability of lipid emulsions in direct proximity to the room where regional anesthesia is performed. METHODS: A standardized survey was sent to 1,305 German hospitals. The main question was whether lipid emulsions are readily available and if published guidelines contributed to this availability. Additionally, we asked whether local anesthetic toxicity had already successfully been treated by lipid emulsions and what type of symptoms were treated. RESULTS: We received replies from n = 509 (39%) hospitals. In 338 (66%) of the responding hospitals, lipid emulsions are readily available. Hospitals with standard operating procedures (SOPs) implemented according to published guidelines have lipids significantly more often immediately available than hospitals with just SOPs (chi-square test of independence, p-value < 0.01). Of all responding hospitals 287 (56%) have implemented a SOP for the treatment of toxic reactions to local anesthetics and 196 (39%) of the hospitals introduced the SOP because of the guidelines. In 28 (6%) of the hospitals, local anesthetic toxicity had already caused cardiac arrest with subsequent cardiopulmonary resuscitation in at least one patient. In 132 (26%) hospitals, local anesthetic toxicity had already been treated by infusing lipid emulsions. Of these hospitals 128 (96%) state this therapeutic approach was successful. Treatment with lipid emulsions was performed frequently after prodromal symptoms 83 (63%) were witnessed. CONCLUSIONS: The majority of surveyed German hospitals are prepared to treat toxic reactions to local anesthetics and published guidelines contributed to this preparedness. The infusion of lipid emulsions is a promising measure to deal with toxic reactions to local anesthetics. Since toxic reactions to local anesthetics are potentially lethal, it seems desirable that lipid emulsions are generally available in routine clinical practice. Currently, the treatment of toxic reactions to local anesthetics is mostly performed in situations (e.g. treatment of prodromal symptoms) that are not recommended by current guidelines. Further research is necessary to better define the future use of lipid emulsions in routine clinical practice.

High serum pentosidine but not esRAGE is associated with prevalent fractures in type 1 diabetes independent of bone mineral density and glycaemic control.

UNLABELLED: Fracture risk in type 1 diabetes (T1D) is supposed to be underestimated by bone mineral density (BMD). Individuals with T1D had more prevalent fractures in a cross-sectional study. Serum levels of pentosidine, an advanced glycation end product, and poor glycaemic control were associated with prevalent fractures independent of BMD. INTRODUCTION: Type 1 diabetes (T1D) is associated with increased fracture risk. Bone mineral density (BMD) underestimates the risk of fractures in some individuals. The accumulation of advanced glycation end products (AGEs) impairs bone matrix and reduces bone strength. METHODS: In a cross-sectional study, 128 men and premenopausal women with T1D were evaluated. We compared traditional risk factors for fractures, BMD, parameters of bone metabolism and AGEs in individuals with and without prevalent fractures. An independent association of serum AGE levels with prevalent fractures was investigated. RESULTS: Individuals with prevalent fractures exhibited a longer duration of T1D, higher HbA1c and more diabetic-related complications. BMD at the femoral neck (z-score -0.76 ± 0.94 vs. -0.23 ± 1.02; p = 0.031) and total hip (z-score -0.54 ± 0.93 vs. 0.11 ± 1.11; p = 0.017) was lower in those with prevalent fractures. Individuals with fractures had higher pentosidine levels (164.1 ± 53.6 vs. 133.2 ± 40.4; p = 0.002). The levels of N-ε-(carboxymethyl)-lysine (CML) and endogenous secretory receptor for AGEs (esRAGE) did not significantly differ. Multivariate logistic regression analysis adjusted for age, BMI, family history of fractures, smoking, vitamin D deficiency, BMD at lumbar spine, femoral neck and total hip identified pentosidine levels and HbA1c as independent factors associated with prevalent fractures (odds ratio 1.02, 95% CI 1.00-1.03/pmol/ml increase of pentosidine; p = 0.008 and odds ratio 1.93, 95% CI 1.16-3.20 per percentage increase of HbA1c; p = 0.011). CONCLUSIONS: The pentosidine levels but not BMD are independently associated with prevalent fractures. Impaired bone quality in T1D may result from increased AGE formation.

B-type natriuretic peptide predicts stroke of presumable cardioembolic origin in addition to coronary artery calcification.

BACKGROUND AND PURPOSE: B-type natriuretric peptide (BNP) is a marker of cardiac dysfunction that is released from myocytes in response to ventricular wall stress. Previous studies suggested that BNP predicts stroke events in addition to classical risk factors. It was suggested that the BNP-associated risk results from coronary atherosclerosis or atrial fibrillation. METHODS: Three thousand six hundred and seventy five subjects from the population-based Heinz Nixdorf Recall study (45-75 years; 47.6% men) without previous stroke, coronary heart disease, myocardial infarcts, open cardiac valve surgery, pacemakers and defibrillators were followed up over 110.1 ± 23.1 months. Cox proportional hazards regressions were used to examine BNP as a stroke predictor in addition to vascular risk factors (age, gender, systolic blood pressure, low-density lipoprotein, high-density lipoprotein, diabetes, smoking), renal insufficiency, atrial fibrillation/known heart failure and coronary artery calcification. RESULTS: Eighty-nine incident strokes occurred (80 ischaemic, 9 hemorrhagic). Subjects suffering stroke had significantly higher BNP values at baseline than the remaining subjects [26.3 (Q1; Q3 = 12.9; 51.0) vs. 17.4 (9.4; 31.4); P < 0.001]. In a multivariable regression, log10 BNP was an independent stroke predictor [hazard ratio 1.96, 95% confidence interval (CI) 1.13-3.41; P = 0.017] in addition to age (1.24 per 5 years, CI 1.04-1.49; P = 0.016), systolic blood pressure (1.25 per 10 mmHg, CI 1.14-1.38; P < 0.001), smoking (2.05, CI 1.24-3.39; P = 0.005), atrial fibrillation/heart failure (2.25, CI 1.05-4.83; P = 0.037) and computed-tomography-based log10 (coronary artery calcification + 1) (1.47, CI 1.15-1.88; P = 0.002). Log10 BNP predicted stroke in men but not women, both in subjects ≤65 and >65 years. In subsequent analyses, BNP discriminated the incidence of cardioembolic stroke (P for trend = 0.001), but not stroke of macroangiopathic (P = 0.555), microangiopathic (P = 0.809) or unknown (P = 0.367) origin. CONCLUSIONS: BNP predicts presumable cardioembolic stroke independent of coronary calcification.

[Medical therapy of heart and lung diseases. Effects on the respective other organ]. / Medikamentöse Therapie von Herz- und Lungenerkrankungen. Effekte auf das jeweils andere Organ.

Many patients suffer from both heart and lung diseases. The choice of medical drugs should not only be driven by the clinical and prognostic effects on the target organ but should also be selected based on the effects on the respective other organ. Beta blockers and statins have both beneficial and harmful effects on the respiratory system. Angiotensin-converting enzyme (ACE) inhibitors and amiodarone can cause severe lung damage. Low-dose thiazides and calcium antagonists are first-line medications in hypertensive asthma patients but beta blockers should be avoided. Theophyline should be used with caution in patients with known cardiac disease. Glucocorticosteroids can cause cardiovascular symptoms while the phosphodiesterase inhibitor roflumilast appears to have no relevant cardiovascular side effects. Anticholinergic drugs have both favorable and unfavorable cardiovascular (side) effects. Short-acting beta-2 sympathomimetic drugs (SABA) and macrolides in particular can trigger arrhythmia and some SABAs are associated with a higher incidence of myocardial infarction. Detailed knowledge of the effects of drugs used for the treatment of lung and heart diseases on the respective other organ and the associated complications and long-term effects are essential in providing optimal medical care to the many patients who present with both respiratory and cardiovascular diseases.

[Joint swelling, reversible arm paresis, and elevated serum IgG4 in a 55-year-old man]. / Gelenkschwellungen, reversible Armparese und erhöhtes Serum-IgG4 bei einem 55-jährigen Patienten.

Only described in the last 10 years, IgG4-related disease is a fibroinflammatory disorder characterized by tumorous lesions with dense lymphoplasmacytic infiltration by IgG4-positive plasma cells and often elevated concentration of serum IgG4. In this paper, we present a male patient with this disease involving the lymph nodes and possibly the joints and kidneys. Infiltration of lymph node tissue with IgG4-positive plasma cells was demonstrated. The general condition of the patient improved considerably by immunosuppressive therapy.

Successful simultaneous stenting of a pulmonary artery and vein in pulmonary vascular stenosis due to silicosis. Case report and literature review.

A 58-year-old patient was admitted to the emergency department due to severe respiratory insufficiency. Anamnesis revealed that the patient had experienced increasing stress dyspnea for a few months. Upon imaging, an acute pulmonary embolism was excluded, but peribronchial and hilar soft tissue proliferation with compression of central parts of the pulmonary circulation was found. The patient had a history of silicosis. The histology report showed tumor-free lymph node particles with prominent anthracotic pigment and dust depositions without evidence of IgG4-associated disease. The patient was administered steroid therapy and underwent simultaneous stenting of the left interlobular pulmonary artery and the upper right pulmonary vein. As a result, a significant improvement in symptoms and physical performance was achieved. The diagnosis of inflammatory or, in particular, fibrosing mediastinal processes can be challenging and important clinical symptoms must be taken into account, especially if the pulmonary vasculature is involved. In such cases, the possibility of interventional procedures should be examined in addition to drug therapy options.

The German Aortic Valve Registry (GARY): a nationwide registry for patients undergoing invasive therapy for severe aortic valve stenosis.

Background The increasing prevalence of severe aortic valve defects correlates with the increase of life expectancy. For decades, surgical aortic valve replacement (AVR), under the use of extracorporeal circulation, has been the gold standard for treatment of severe aortic valve diseases. In Germany ~12,000 patients receive isolated aortic valve surgery per year. For some time, percutaneous balloon valvuloplasty has been used as a palliative therapeutic option for very few patients. Currently, alternatives for the established surgical procedures such as transcatheter aortic valve implantation (TAVI) have become available, but there are only limited data from randomized studies or low-volume registries concerning long-time outcome. In Germany, the implementation of this new technology into hospital care increased rapidly in the past few years. Therefore, the German Aortic Valve Registry (GARY) was founded in July 2010 including all available therapeutic options and providing data from a large quantity of patients.Methods The GARY is assembled as a complete survey for all invasive therapies in patients with relevant aortic valve diseases. It evaluates the new therapeutic options and compares them to surgical AVR. The model for data acquisition is based on three data sources: source I, the mandatory German database for external performance measurement; source II, a specific registry dataset; and source III, a follow-up data sheet (generated by phone interview). Various procedures will be compared concerning observed complications, mortality, and quality of life up to 5 years after the initial procedure. Furthermore, the registry will enable a compilation of evidence-based indication criteria and, in addition, also a comparison of all approved operative procedures, such as Ross or David procedures, and the use of different mechanical or biological aortic valve prostheses.Results Since the launch of data acquisition in July 2010, almost all institutions performing aortic valve procedures in Germany joined the registry. By now, 91 sites which perform TAVI in Germany participate and more than 15,000 datasets are already in the registry.Conclusion The implementation of new or innovative medical therapies needs supervision under the conditions of a well-structured scientific project. Up to now relevant data for implementation of TAVI and long-term results are missing. In contrast to randomized controlled trials, GARY is a prospective, controlled, 5-year observational multicenter registry, and a real world investigation with only one exclusion criterion, the absence of patients' written consent.

Glycaemic control is positively associated with prevalent fractures but not with bone mineral density in patients with Type 1 diabetes.

AIM: There are conflicting data regarding the risk of osteoporosis in patients with Type 1 diabetes. We investigated an association between diabetes, bone mineral density and prevalent fractures. METHODS: A single-centre, cross-sectional study of men and pre-menopausal women with Type 1 diabetes (n = 128) and a matched control group (n = 77) was conducted. The primary outcome measure was bone mineral density and secondary measures were markers of bone metabolism and prevalent fractures. RESULTS: Hip and total body bone mineral densities were significantly lower in women with diabetes compared with control subjects. In men, no difference in bone mineral density was found. A multivariate regression analysis in women with diabetes revealed higher BMI as the strongest predictor of higher total hip, femoral neck and total body bone mineral density, whereas previous fractures were inversely associated with total hip bone mineral density and C-terminal telopeptide of type I collagen with total body bone mineral density. Poor long-term glycaemic control was not associated with low bone mineral density. Fracture frequency was higher in patients with diabetes compared with control subjects (1.64 vs. 0.62 per 100 patient-years; P < 0.05). In a multivariable model, long-term HbA(1c) control was associated with increased clinical fracture prevalence (OR 1.92; 95% CI 1.09-2.75) in those with diabetes. CONCLUSIONS: Type 1 diabetes contributes to low bone mineral density in women. Previous fractures and low BMI were strong predictors of impaired bone mineral density and should therefore be considered in risk estimation. Fractures are more frequent in Type 1 diabetes. Long-term hyperglycaemia may account for impaired bone strength, independently from bone mineral density.

Pericardial effusion of HIV-infected patients ? Results of a prospective multicenter cohort study in the era of antiretroviral therapy.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular diseases. Previous publications described pericardial effusion as one of the most common HIV-associated cardiac affiliations. The aim of the current study was to investigate if pericardial effusion still has a relevant meaning of HIV-infected patients in the era of antiretroviral therapy. METHODS: The HIV-HEART (HIV-infection and HEART disease) study is a cardiology driven, prospective and multicenter cohort study. Outpatients with a known HIV-infection were recruited during a 20-month period in a consecutive manner from September 2004 to May 2006. The study comprehend classic parameters of HIV-infection, comprising CD4-cell count (cluster of differentiation) and virus load, as well as non-invasive tests of cardiac diseases, including a thorough transthoracic echocardiography. RESULTS: 802 HIV-infected patients (female: 16.6%) with a mean age of 44.2 ± 10.3 years, were included. Duration of HIV-infection since initial diagnosis was 7.6 ± 5.8 years. Of all participants, 85.2% received antiretroviral therapy. Virus load was detectable in 34.4% and CD4 - cell count was in 12.4% less than 200 cells/µl. Pericardial effusions were present in only two patients of the analysed population. None of the participants had signs of a relevant cardiovascular impairment by pericardial effusion. CONCLUSIONS: Our results demonstrate that the era of antiretroviral therapy goes along with low rates of pericardial effusions in HIV-infected outpatients. Our findings are in contrast to the results of publications, performed before the common use of antiretroviral therapy.

[Coronary artery disease in HIV-infected subjects. Results of 101 coronary angiographies]. / Koronare Herzerkrankung bei HIV-infizierten Personen. Ergebnisse von 101 Koronarangiographien.

BACKGROUND: The introduction of antiretroviral therapy has brought cardiac disease as a comorbidity in HIV-infected patients in particular into focus. The present study analyses the results of coronary angiography in this patient population. METHODS: Over a time period of 12 years, 101 coronary angiographies were performed in HIV-infected patients. A retrospective analysis included demographic parameters, cardiac history, cardiovascular risk factors, HIV-specific parameters including antiretroviral therapy and the results of coronary angiographies. RESULTS: Of the subjects included in the study, 89% were men. The mean age in the analysed population was 50.2 years at the time of coronary angiography. Patients had an elevated rate of cardiovascular risk factors including diabetes mellitus (15.9%), arterial hypertension (65.9%), hyperlipidemia (56.8 %) and smoking (68.2 %). Primary coronary angiography demonstrated coronary disease in 59.1%. Of all patients with coronary artery disease, 70% underwent coronary intervention. Subjects who underwent coronary intervention exhibited hyperlipidemia significantly more often (77.8% vs. 42.3%, p=0.02). Cardiovascular risk factors play a prominent role in the development of premature arteriosclerosis in HIV-infected patients. Furthermore, our data highlight the importance of invasive diagnostics in this patient group.

Combination therapy with dexamethasone and osteoprotegerin protects against arthritis-induced bone alterations in antigen-induced arthritis of the rat.

OBJECTIVE: To investigate the influence of a combined therapy consisting of dexamethasone and osteoprotegerin (OPG) on bone alterations and disease activity in antigen-induced arthritis (AIA) in the rat. METHODS: AIA rats received dexamethasone (0.25 mg kg(-1) day(-1), i.p.), OPG (2.5 mg kg(-1) day(-1), i.p.), or a combination of both at regular intervals for 21 consecutive days. At the end of the treatment, bone structure was analyzed by histomorphometry. Primary spongiosa was measured using linear scanning. RESULTS: AIA led to significant periarticular and axial bone loss. Dexamethasone monotherapy substantially suppressed joint swelling without inhibiting bone loss of the secondary spongiosa, whereas OPG monotherapy showed no anti-inflammatory effect. Despite reduction of bone resorption, OPG did not inhibit AIA-induced bone loss. In contrast, the combination of dexamethasone and OPG not only produced an anti-inflammatory effect, but also resulted in inhibition of periarticular and axial bone loss. OPG increased trabecular number of the primary spongiosa whilst combination therapy led to an increase in both trabecular number and trabecular width. CONCLUSION: The principle of combining a glucocorticoid together with inhibition of the receptor activator of NF-kappaB ligand (RANKL) may be an effective bone-saving therapy in rheumatoid arthritis.

[Cost-effectiveness of study nurses in the management of patients with heart failure. A systematic review]. / Kosteneffektivität des Einsatzes von Studienschwestern in der Betreuung von Patienten mit Herzinsuffizienz.

BACKGROUND AND PURPOSE: Heart failure is currently one of the most common and cost-intensive diseases. Furthermore, high morbidity and mortality are distinctive for this disease. Therefore, new treatment programs are increasingly developed; especially the care of heart failure patients by specialized nurses (study nurses) represents a frequent new concept. This review gives a systematic overview of the cost-effectiveness of new treatment concepts with study nurses in comparison to the conventional care of heart failure. METHODS: A systematic literature search in MEDLINE was performed for the period from 1995 till April 2008. The search strategy included terms from three essential areas relating to the working subject: twelve search keys with regard to the clinical picture, 21 words concerning the intervention with study nurses, and 27 terms with reference to health economics. The literature selection was carried out on the basis of a priori defined in- and exclusion criteria. Economic evaluations based on randomized controlled trials with a study duration of at least 6 months which were published in English or German were enclosed. An extraction of the relevant data as well as a qualitative synthesis of information were conducted. RESULTS: A total of 13 studies were identified. With five of nine of the enclosed publications, a statistically significant reduction of the number of all-cause rehospitalizations was reported. Two of twelve publications showed a statistically significant decrease in mortality in favor of the intervention group. Twelve of 13 publications only reported the costs and effects of both groups separately. For the five of nine publications with significant reductions of rehospitalization, an own calculation of the incremental cost-effectiveness ratio (ICER) could be carried out based on the cost and effect data. It turned out an ICER of costs at the rate of 490 Euros up to savings of 7,330 Euros per prevented rehospitalization. CONCLUSION: This systematic review shows an international trend that concepts for the care of patients with heart failure that involve study nurses are cost-effective. For the German context there are no comparable data available.