Vertebral osteomyelitis is characterised by increased RANK/OPG and RANKL/OPG expression ratios in vertebral bodies and intervertebral discs.

Vertebral osteomyelitis (VO) is an infection of the spine mainly caused by bacterial pathogens. The pathogenesis leading to destruction of intervertebral discs (IVDs) and adjacent vertebral bodies (VBs) is poorly described. The present study aimed at investigating the connection between infection and bone/disc metabolism in VO patients. 14 patients with VO (infection group) and 14 patients with burst fractures of the spine (fracture group; control) were included prospectively. Tissue biopsies from affected IVDs and adjacent VBs were analysed by RT-qPCR for mRNA-expression levels of 18 target genes including chemokines, adipokines and genes involved in bone metabolism. Most importantly, the receptor activator of NF-κB/osteoprotegerin (RANK/OPG) expression ratio was drastically elevated in both VBs and IVDs of the infection group. In parallel, expression of genes of the prostaglandin-E2-dependent prostanoid system was induced. Such genes regulate tissue degradation processes via the triad OPG/RANK/RANKL as well as via the chemokines IL-8 and CCL-20, whose expression was also found to be increased upon infection. The gene expression of the adipokine leptin, which promotes inflammatory tissue degradation, was higher in IVD tissue of the infection group, whereas the transcription of omentin and resistin genes, whose functions are largely unknown in the context of infectious diseases, was lower in infected VBs. In summary, similar expression patterns of pro-inflammatory cytokines and pro-osteoclastogenic factors were identified in VBs and IVDs of patients suffering from VO. This suggests that common immuno-metabolic pathways are involved in the mechanisms leading to tissue degradation in VBs and IVDs during VO.

[99cmTc]Tc-PSMA-I&S-SPECT/CT: experience in prostate cancer imaging in an outpatient center.

BACKGROUND: Prostate-specific membrane antigen (PSMA) SPECT imaging in prostate cancer (PCa) could be a valuable alternative in regions where access to PSMA-PET imaging is restricted. [99mTc]Tc-PSMA-I&S is a new 99mTc-labeled PSMA-targeting SPECT agent, initially developed for radio-guided surgery. We report on the diagnostic use of [99mTc]Tc-PSMA-I&S-SPECT/CT in PCa. RESULTS: [99mTc]Tc-PSMA-I&S-SPECT/CT was performed and evaluated in 210 outpatients with PCa at a single center. Patients were imaged for biochemical recurrence (BCR, n = 152, mean PSA 8.7 ng/ml), for primary staging of high-risk PCa (n = 12, mean PSA 393 ng/ml), and restaging in advanced recurrent PCa (n = 46, mean PSA 101.3 ng/ml). Number and location of positive lesions were determined for the different subgroups. For BCR, detection rates were calculated, defined as the proportion of scans with at least one PSMA-positive lesion. PSMA positive lesions were detected in 65.2% of all 210 patients. Tumor tissue was mainly detected in lymph nodes (59%), in the bone (42%), and in the prostate (fossa) (28%). In the subgroup of patients referred for detection of BCR the detection rate increased from 20% at a PSA level < 1 ng/ml to 82.9% and 100% at PSA levels > 4 ng/ml and > 10 ng/ml, respectively. In the subgroup of high-risk patients referred for primary staging, 42% demonstrated metastatic disease. Restaging of advanced recurrent PCa revealed detectability of PSMA positive tumor lesions in 85% of the scans. CONCLUSIONS: [99mTc]Tc-PSMA-I&S-SPECT/CT was useful in PSMA-targeted imaging of PCa at various clinical stages. At low PSA levels (< 4 ng/ml), detection rates of [99mTc]Tc-PSMA-I&S-SPECT/CT in BCR are clearly inferior to data reported for PET-imaging and should thus only be considered for lesion detection if imaging with PET is unavailable. However, at higher PSA levels (> 4 ng/ml) [99mTc]Tc-PSMA-I&S-SPECT/CT provides high detection rates in BCR. [99mTc]Tc-PSMA-I&S-SPECT/CT can also be used for primary staging and for restaging of advanced recurrent PCa. However, further studies are needed to assess the clinical value in these indications.

Tumor-on-a-chip for integrating a 3D tumor microenvironment: chemical and mechanical factors.

Tumor progression, including metastasis, is significantly influenced by factors in the tumor microenvironment (TME) such as mechanical force, shear stress, chemotaxis, and hypoxia. At present, most cancer studies investigate tumor metastasis by conventional cell culture methods and animal models, which are limited in data interpretation. Although patient tissue analysis, such as human patient-derived xenografts (PDX), can provide important clinical relevant information, they may not be feasible for functional studies as they are costly and time-consuming. Thus, in vitro three-dimensional (3D) models are rapidly being developed that mimic TME and allow functional investigations of metastatic mechanisms and drug responses. One of those new 3D models is tumor-on-a-chip technology that provides a powerful in vitro platform for cancer research, with the ability to mimic the complex physiological architecture and precise spatiotemporal control. Tumor-on-a-chip technology can provide integrated features including 3D scaffolding, multicellular culture, and a vasculature system to simulate dynamic flow in vivo. Here, we review a select set of recent achievements in tumor-on-a-chip approaches and present potential directions for tumor-on-a-chip systems in the future for areas including mechanical and chemical mimetic systems. We also discuss challenges and perspectives in both biological factors and engineering methods for tumor-on-a-chip progress. These approaches will allow in the future for the tumor-on-a-chip systems to test therapeutic approaches for individuals through using their cancerous cells gathered through approaches like biopsies, which then will contribute toward personalized medicine treatments for improving their outcomes.

Author Correction: Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

[Dacryoliths and Iatrogenic Foreign Bodies as Classical Triggers for Inflammatory Pseudotumors of the Lacrimal Drainage System]. / Dakryolithen und iatrogene Fremdkörper als klassische Auslöser entzündlicher Pseudotumoren der ableitenden Tränenwege.

BACKGROUND: Tumors of the lacrimal duct are rare. Inflammatory pseudotumors do not represent neoplasias as such. Chronic inflammation may lead to an angiomatous granulation tissue. PATIENTS: The first case presents a 53-year-old male patient suffering a mass of the mediocaudal orbit after an acute dacryocystitis has been cured. Using diagnostic dacryoendoscopy, a large dacryolith was detected. Removing the concrement, via external dacryocystorhinostomy, a polypous tissue appeared which was resected as well. The second case concerns a 29-year-old female patient. She had a lacrimal surgery with stenting seven years prior to surgery. The patient's history revealed recurrent mucous secretion of the tear duct and tenderness of the lacrimal sac. An intrasaccal silicon foreign body could be confirmed by dacryoendoscopy. An external dacryocystorhinostomy was performed and the material was extracted. Hereby, an inflammatory tissue mass filling the whole efferent tear duct was removed. RESULTS: In both patients, external dacryocystorhinostomy was performed complication-free. Surgery enabled the reconstruction of the nasolacrimal duct. Temporary autostable silicon intubation was inserted into the nasolacrimal duct (case 1 and 2), as well into osteotomy (case 2). Histologically, reactive granulation tissue was confirmed. During the follow-up of 9 months (patient 1) and 12 months (patient 2), patients were free of complaints. Lacrimal stentings were removed uneventfully and completely. CONCLUSIONS: Dacryoliths and intrasaccal foreign bodies may cause a chronic dacryocystitis. Due to inflammation, reactive tissue proliferation can be initiated. In these cases, a hypertrophic granulation arose. Endogenous (dacryoliths) and exogenous (iatrogenic foreign bodies) triggers may be underlying reasons. Histological examination is essential for differentiating other inflammatory pathologies or tumors.

Mimicking Embedded Vasculature Structure for 3D Cancer on a Chip Approaches through Micromilling.

The ability for cells to sense and respond to microenvironmental signals is influenced by their three dimensional (3D) surroundings, which includes the extracellular matrix (ECM). In the 3D environment, vascular structures supply cells with nutrients and oxygen thus affecting cell responses such as motility. Interpretation of cell motility studies though is often restricted by the applied approaches such as 2D conventional soft lithography methods that have rectangular channel cross-sectional morphology. To better simulate cell responses to vascular supply in 3D, we developed a cell on a chip system with microfluidic channels with curved cross-sections embedded within a 3D collagen matrix that emulates anatomical vasculature more closely than inorganic polymers, thus to mimic a more physiologically relevant 3D cellular environment. To accomplish this, we constructed perfusable microfluidic channels by embedding sacrificial circular gelatin vascular templates in collagen, which were removed through temperature control. Motile breast cancer cells were pre-seeded into the collagen matrix and when presented with a controlled chemical stimulation from the artificial vasculature, they migrated towards the vasculature structure. We believe this innovative vascular 3D ECM system can be used to provide novel insights into cellular dynamics during multidirectional chemokineses and chemotaxis that exist in cancer and other diseases.

What Is the Best Treatment before Bariatric Surgery? Exercise, Exercise and Group Therapy, or Conventional Waiting: a Randomized Controlled Trial.

OBJECTIVE: This trial's objective was to investigate the effect of an exercise program with and without cognitive-behavioral therapy (CBT), compared by a control group, on weight, functional capacity, and cardiometabolic profile of morbidly obese individuals while waiting for bariatric surgery. MATERIALS AND METHODS: This randomized controlled trial investigated the effect of a 4-month low-intensity exercise program (two weekly sessions of 25 min each) on 66 morbidly obese individuals awaiting bariatric surgery. Participants were randomly divided into three groups: EXER, exercise program; EXER + CBT, exercise program plus support group sessions for lifestyle modification, with a CBT; and CONTROL, routine treatment. They were compared on weight, functional capacity, and cardiometabolic profile. RESULTS: The weight change (Kg) was -7.4 (-9.6 to 5,1); -4,2 (-6,8 to -1.6) and 2.9 (0.4 to 5.3) and the BMI change (kg/m2) was -2.7 (-3.6 to -1.8); -1.4 (-2.4 to -0.4) and 1.1 (0.1 to 2.1) for groups EXER, EXER + CBT, and CONTROL, respectively. Changes were significant when compared to the control group (p < 0.001), but there were no differences between the two intervention arms (p = 0.2). Functional capacity and cardiometabolic parameters significantly improved in the intervention arms and worsened in the control group. The adherence to the exercise program in both groups was above 78 %. CONCLUSION: A 4-month, twice-weekly supervised program of low-intensity physical activity that encourages individuals to adopt a more active lifestyle can positively interfere with weight loss and improvement in functional capacity and cardiometabolic parameters of morbidly obese individuals with and without the aid of support group sessions.

Análisis de instrumento para evaluación del desempeño en actividades de la vida diaria instrumentales Lawton y Brody / Analysis of the Lawton and Brody instrumental activities of daily living assessment instrument

El propósito fue analizar el Índice de Lawton y Brody (ILB), determinando si los factores género, desempeño previo y nivel socioeconómico afectan las conclusiones relacionadas con la dependencia en AVDI. La metodología es analítica, exploratoria y transversal. En primera instancia se aplicó una encuesta de percepción de ILB a 22 terapeutas ocupacionales (TTOO) pertenecientes a servicios públicos de Valparaíso, Viña del Mar, Concón y Quilpué. En segunda instancia se aplicó ILB más un cuestionario complementario a 36 usuarios del Centro Comunitario de Rehabilitación de Miraflores, Instituto deNeurorehabilitación Luis Krebs y Centro de Rehabilitación Integral Siloe; paralelamente, el terapeuta ocupacional (TO) completó una encuesta con su impresión sobre la capacidad de realizar las AVDI de sus usuarios, para determinar diferencias significativas entre ambos. Resultados: Los resultados indican que los TO están en desacuerdo con las características del instrumento. En los resultados de su aplicación, el ILB permite identificar el nivel de dependencia en AVDI en los ítems que evalúa. Se condujó que el factor género no es determinante de la dependencia, pero sí es determinante el factor socioeconómico; el nivel de desempeño previo tiene una correlación positiva con el desempeño actual de las personas. Conclusiones: La percepción de los TO está en desacuerdo con ILB. Los resultados de la aplicación de ILB y la contrastación con la impresión del TO tratante permite confirmar que efectivamente el instrumento logra el objetivo para el cual fue diseñado, destacando que el género no es un factor determinante en la realización de AVDI, mientras el factor socioeconómico es considerado como relevante para su realización.

The aim was to analyze the Lawton and Brody index (LBI), to determine if factors such as gender, previous performance and socio-economic level affect the conclusions related to the IADL dependency. The methodology is analytic, exploratory and cross-sectional. An opinion survey about IADL was applied to 22 OTs belonging to public services in Valparaíso, Viña del Mar, Concón and Quilpué. The LBI plus a 36-question complementary questionnaire were applied to Rehabilitation Community Center in Miraflores, Luis Krebs Neuro-rehabilitation Institute and Comprehensive Rehabilitation Center. Besides, the OTs filled in a survey about his views on the users’ abilities to perform IADL in order to establish meaningful differences between both. Results: The results show that occupational therapists don’t agree with the instrument features. In the results application, the LBI allows to identify the dependency level in IADL in the assessed items. It was shown that the gender factor is not decisive in dependency, however, the socio-economic factor is decisive; the level of previous performance has a positive correlation with the people’s current performance. Conclusions: The OT’s perception shows disagreement with the BLI. The results of the application of LBI and the contrast with the OTs opinion allows to confirm that the instrument actually fulfills the objective for which it was designed, pointing out that gender is not a decisive factor in IADL while socio economic factor is considered relevant in its application.

[New regulations for inpatient treatment of the statutory accident insurance: From the perspective of a university medical center]. / Neuordnung des stationären Heilverfahrens der Gesetzlichen Unfallversicherung: Aus Sicht einer Universitätsklinik.

BACKGROUND: New regulations of the German statutory accident insurance for inpatient treatment have been introduced. The aims of the new regulations are to improve cost-effectiveness and the quality of medical care. The introduction of the injury type catalogue and the severe injuries type procedure (SAV) has led to a concentration of resources. The purpose of these innovations is an increase in the quality of treatment of patients with complex injuries. CONCLUSION: The introduction of the new regulations resulted in a centralization of medical care in order to optimize the quality of treatment of complex injuries from occupational accidents. Hence, the high demands concerning infrastructure and human resources expected of a level one university medical center are taken into account.

Dignidad ocupacional en personas con secuelas secundarias a daño neurológico severo / Occupational dignity in people with side effects to severe neurological damage

La terapia ocupacional es una disciplina socio sanitaria difícil de definir y explicar por su amplio espectro de acción, diversos autores han hecho distintas definiciones de ésta, sin embargo aún cuesta que la sociedad general entienda y conozca el significado de esta profesión, que desde un enfoque contemporáneo está centrada en la participación ocupacional de las personas. (Crepeau, 2011)Tiene como objetivo principal dotar a los individuos, organizaciones o poblaciones que interviene, de los recursos necesarios para su bienestar ocupacional, aprovechando todas las capacidades individuales, colectivas, los recursos cotidianos y el entorno para esto. Según los planteamientos de la Asociación Americana de Terapia Ocupacional, la terapia ocupacional asegura el compromiso con la justicia ocupacional (Aviles, 2010) de las personas, lo cual quiere decir, que indistinto de las características de la situación de discapacidad que presenta una persona, éstas tienen el derecho a lograr participar de las ocupaciones humanas. Esto se vincula con un concepto mayor, propio a la característica de humanidad de nuestra especie, la cual se denomina dignidad humana, a partir de estos dos términos, la experiencia clínica y académica de las autoras en intervención de personas con secuelas secundarias a daño neurológico severo, generan el concepto Dignidad Ocupacional, que hace referencia a que toda persona tiene derecho a disfrutar dignamente de experiencias ocupacionales a pesar de no contar con las destrezas de desempeño necesarias para involucrarse en ellas de manera independiente...

Occupational Therapy is a socio-health discipline which is difficult to define and explain due to its wide range of action. Several authors have defined it, however it is still hard for society to understand and know the meaning of this profession, which from a contemporary approach, is focused on the occupational participation of people (Crepeau, 2011).Its main objective is to deal with individuals, organizations and population to provide the necessary resources for their occupational welfare, taking advantage of all individual and group capacities, as well as daily resources and environment. According to the statements of the American Occupational Therapy Association , occupational therapy ensures the commitment to occupational justice (Aviles, 2010) with people , that is ,no matter the characteristics of the disability situation of a given person, she or he has the right to participate in human occupations. This goes along with a major concept that is inherent to our species human characteristic: human dignity, notion based on considering a person able to offer options to improve the quality of life, independent of his or her condition When it comes to people suffering from severe neurological damage, it is often believed that they only need to satisfy their basic self-care needs, nevertheless, they are people subject to rights, worthy and who deserve equal treatment. Thus, the effort to satisfy the occupations they cannot do by themselves is what we call Occupational Dignity, concept that was born with the blending of human dignity and occupational justice...

[The relevant axial deviation: Diagnostics and therapy for correction osteotomies of the femur]. / Die relevante Achsabweichung : Diagnostik und Therapie bei Korrektureingriffen am Femur.

Intraoperative assessment of the femoral axis, length and torsion can be difficult. A postoperative torsional discrepancy is a common but rarely diagnosed condition. A clinical evaluation of femoral torsion is limited, especially in the early postoperative period. Conventional radiographs are a reliable diagnostic tool for evaluation of discrepancies of leg length and axis. Computed tomography remains the gold standard for assessment of torsional discrepancies. Because of the wide variability of the physiological femoral torsion, the clinical impact of a torsional discrepancy in individual cases remains unclear. There is a general recommendation for revision in cases of intraindividual deviations of more than 15°; however, most patients with deviations even greater than 15° are asymptomatic. Therefore, the indications for correction should be carefully considered in each individual case. The patient level of activity is a crucial point in decision-making for correction osteotomy. Before correction osteotomy, the surgeon has to make a detailed biomechanical analysis of the leg. Early correction is recommended in most cases. Detailed knowledge of the patient medical history is needed for preoperative planning. Prior surgeries can have a significant impact on the choice of the surgical approach and stabilization technique.

Stress hormones reduce the efficacy of paclitaxel in triple negative breast cancer through induction of DNA damage.

BACKGROUND: The mechanisms by which stress hormones impact triple-negative breast cancer (TNBC) etiology and treatment are unclear. We have previously shown that stress hormones, cortisol, and catecholamines induce rapid DNA damage and impact DNA repair in NIH 3T3 fibroblasts. This study investigates whether stress hormones increase DNA damage in breast cancer cells and if this impacts drug efficacy. METHODS: We first screened a panel of 39 breast cancer cell lines for expression of adrenergic and glucocorticoid receptors and examined if stress hormones induce DNA damage and alter cell cycle regulation in vitro. A TNBC xenograft model was used to assess the impact of restraint stress on tumour growth and chemosensitivity to paclitaxel. RESULTS: We found that stress hormones induced DNA damage, phosphorylation of ATR, which was accompanied by an up-regulation of the G1 cell kinase inhibitor p21 and a cell cycle halt of TNBCs in the G1 phase. p21 knockdown abrogated G1 arrest by stress hormones. We also demonstrated that stress significantly decreased efficacy of paclitaxel. CONCLUSION: We describe a novel mechanism through which stress hormones can induce drug resistance to paclitaxel, which may have profound implications for treating drug resistance in patients with TNBC.

Factor XI replacement for inherited factor XI deficiency in routine clinical practice: results of the HEMOLEVEN prospective 3-year postmarketing study.

Factor XI (FXI)-deficient patients may develop excessive bleeding after trauma or surgery. Replacement therapy should be considered in high-risk situations, especially when FXI levels are below 20 IU dL(-1) . HEMOLEVEN is a human plasma-derived factor XI concentrate available in France since 1992, but there are few data regarding its use by physicians. This prospective study assessed the use, efficacy and safety of HEMOLEVEN in common clinical practice. HEMOLEVEN was evaluated in FXI-deficient patients in 13 French centres in a 3-year postmarketing study. Forty-four patients (30 females, 14 males) received 67 treatments. The median age was 37 years (8 months-91 years). Basal FXI levels were <1 to 51 IU dL(-1) (median: 5.5); 29 patients were severely FXI-deficient (<20 IU dL(-1) ). FXI was administered prophylactically before 43 surgical procedures, 10 invasive procedures, 8 vaginal deliveries, or as curative treatment for six bleeds. The efficacy was assessed as excellent/good in 63, moderate in two and undetermined in two treatments. Seven patients experienced seven adverse effects, including two rated as serious: one sudden massive pulmonary embolism with fatal outcome and one case of inhibitor to FXI. HEMOLEVEN is effective for bleeding prevention in FXI deficiency. However, considering the benefit/risk ratio observed in relation to dosage in this study; firstly, it should be used sparingly due to its potential prothrombotic effect; secondly, new prescription procedures should be defined to adapt the dosage, especially in patients with intrinsic and/or acquired risk factors for thrombosis.

How to optimize lipoprotein apheresis treatment--a second look.

BACKGROUND: Lipoprotein apheresis (LA) is used in hypercholesterolemic patients suffering from cardiovascular disease (CHD) if a modified diet and lipid-lowering drug regimens had failed. During the first LA treatments LDL-cholesterol (LDL-C) and lipoprotein (a) (Lp(a)) can be decreased very effectively when using generally accepted formulas for calculating plasma (PV) (e.g. Pearson) or blood volumes (BV) as a basis for calculating treatment volume (e.g. Nadler). With respect to LDL-C and Lp(a) levels after LA treatment not all treated patients on steady state with apheresis treatment procedures may achieve the desired target concentrations for LDL-C (<70 mg/dl) and Lp(a) (<30 mg/dl). Are there further ways to increase the effectiveness of LA? METHODS: Over months or years of LA the treated volumes were stepwise increased in patients to achieve target cholesterol concentrations but not sufficiently in all cases. Therefore the patients' actual LA treatment volumes were compared to the calculated PV or BV. To possibly optimize the treatment capacity of LA procedures independent of calculated PV or BV the capacity threshold was determined in addition. During LA procedures every 20 min cholesterol, triglycerides, LDL-C, HDL-C and Lp(a) concentrations were determined and related to the hematocrit to exclude dilution effects. RESULTS: In patients undergoing regular LA treated volumes vs. calculated volumes were different: for PV 28 ± 18% (n = 7); for BV 28 ± 20% (n = 6). The mean treated volumes were 1.3 fold larger than the calculated volumes to achieve cholesterol target levels in most LA treatments. With respect to the capacity threshold we observed in only 1 of 13 patients an ineffective long treatment time. No LA procedure failed due to exhausted capacity. CONCLUSIONS: Lipoprotein apheresis treatment is a very effective treatment procedure in lowering LDL-C and Lp(a). However, not in all procedures the optimal treatment volume for LA patients may be calculated. However calculations of PV and BV are more or less error-prone. An increase of 1.3 fold in the calculated volumes may be the first step in optimizing individual LA treatment options. In addition, to exclude an exhaustion of LA procedures the determination of the individual capacity threshold in every LA patient may be further helpful to adjust treatment volumes. To substantiate our demand on changed treatment volumes further data are necessary.

Role for Prdx1 as a specific sensor in redox-regulated senescence in breast cancer.

Recent studies suggest that Peroxiredoxin 1 (Prdx1), in addition to its known H2O2-scavenging function, mediates cell signaling through redox-specific protein-protein interactions. Our data illustrate how Prdx1 specifically coordinates p38MAPK-induced signaling through regulating p38MAPKα phosphatases in an H2O2 dose-dependent manner. MAPK phosphatases (MKP-1 and/or MKP-5), which are known to dephosphorylate and deactivate the senescence-inducing MAPK p38α, belong to a group of redox-sensitive phosphatases (protein tyrosine phosphatases) characterized by a low pKa cysteine in their active sites. We found that Prdx1 bound to both MKP-1 and MKP-5, but dissociated from MKP-1 when the Prdx1 peroxidatic cysteine Cys52 was over-oxidized to sulfonic acid, which in turn resulted in MKP-1 oxidation-induced oligomerization and inactivity toward p38MAPKα. Conversely, over-oxidation of Prdx1-Cys52 was enhancing in the Prdx1:MKP-5 complex with increasing amounts of H2O2 concentrations and correlated with a protection from oxidation-induced oligomerization and inactivation of MKP-5 so that activation toward p38MAPK was maintained. Further examination of this Prdx1-specific mechanism in a model of reactive oxygen species-induced senescence of human breast epithelial cells revealed the specific activation of MKP-5, resulting in decreased p38MAPKα activity. Taken together, our data suggest that Prdx1 orchestrates redox signaling in an H2O2 dose-dependent manner through the oxidation status of its peroxidatic cysteine Cys52.

Current view: indications for extracorporeal lipid apheresis treatment.

BACKGROUND: One of the first investigations concerning extracorporeal treatment of hypercholesterolemia was performed in 1967 by plasma exchange in patients with homozygous or severe heterozygous familial hypercholesterolemia (FH). In the following decades, several specific lipid apheresis systems were developed to efficiently eliminate low-density lipoprotein (LDL) cholesterol and Lp(a) cholesterol in hypercholesterolemic patients. In the early 1980s, the main clinical indication has been homozygous FH including mainly children and pregnant women. In consideration of the current development of lipid-lowering regimens and scientific knowledge of preventing progression of cardiovascular diseases, the spectrum of indications to initiate lipid apheresis was extended due to still insufficient lipid-lowering therapy in some clinical cases. However, a generally accepted indication for lipid apheresis treatment is still under discussion. In Germany, the target-oriented distribution of increasingly limited healthcare resources demand data which support the benefit of established treatment procedures such as lipid apheresis. In recent years, the Federal Joint Committee (G-BA), a paramount decision-making body of the German Healthcare System, issued to reassess the approval of chronic lipid apheresis therapy for regular reimbursement. Therefore, in 2005, an interdisciplinary German Apheresis Working Group has been established by members of both the German societies of nephrology. One of the first goals of this working group was a revision of the indications for lipid apheresis corresponding to current guidelines and recommendations for the treatment of lipid disorders. In addition, recently new pathophysiological perceptions of the impact of lipoproteins on atherogenesis and thrombosis were also considered. METHODS AND RESULTS: Since 2005, the working group met on a regular basis to substantiate the first defined goals. The indications for lipid apheresis were critically revised with respect to actual results from clinical investigations, cardiovascular guidelines, and scientific knowledge and were accepted by the members of the apheresis working group. CONCLUSIONS: There is consensus between the medical societies and health insurance funds regarding the need for general accepted guidelines for lipid apheresis. Recommendations for the indications of lipid apheresis were developed, but additionally these results should be confirmed by medical societies to transform them to guidelines. However, due to limited data showing that lipid apheresis has effects on the progression of cardiovascular diseases all members of the apheresis working group support a project for creating a lipid apheresis registry. This apheresis registry has been developed and recently started. The primary goal is to substantiate prospective long-term data on clinical outcome of chronic lipid apheresis treatment and to support additional clinical research activities in this field. In addition, this registry should comply with the actual requests of the Federal Joint Committee (G-BA).

Validation study of the "Sniffin' Sticks" olfactory test in a British population: a preliminary communication.

OBJECTIVE: The 'Sniffin' Sticks' olfactory test contains pen-like odour dispensing devices which are used to assess olfactory threshold, discrimination and identification. Odour identification is strongly dependent on familiarity with the odours and has an important cultural component which has limited the usefulness of other validated tests. The 'Sniffin' Sticks' test was developed in Germany and is validated in other countries but not in the UK. This study aims to validate the applicability of 'Sniffin' Sticks' in a local population. DESIGN: Prospective controlled study. SETTING: Rhinology or olfactory disorder clinic. PARTICIPANTS: About 82 subjects, 33 healthy volunteers with a reported normal sense of smell, and 49 patients with an impaired sense of smell presenting either at a rhinology or an olfactory disorder clinic. Each subject's olfactory function was assessed using the 'Sniffin' Sticks' test with a maximum score of 48. MAIN OUTCOME MEASURES: Threshold, discrimination and identification scores along with the combined olfactory score. RESULTS: The mean age of the subjects tested was 46.7 years; 46 female and 36 male. In the patient group 36 were hyposmic and 13 anosmic. In the healthy volunteers group all subjects were normosmic. In the control group the mean combined olfactory score was 34.5 (±2.5). The mean combined score in the patients group was 20.8 (±7.4). Odour threshold scores were 3.7(±2.8) for patients (hyposmics and anomics) and 8.3(±1.8) for controls. In the identification test the controls mean score was 13.6 (±1.2) for while the patients' mean score was 8.6 (±3.5). CONCLUSIONS: In our sample of the local population the combined olfactory and odour identification scores for healthy volunteers and patients with olfactory disorders are comparable with the normative data published on large samples of European populations. However, modification of a few of the distracters is recommended for British patients based on our findings.