Nab-paclitaxel weekly versus dose-dense solvent-based paclitaxel followed by dose-dense epirubicin plus cyclophosphamide in high-risk HR+/HER2- early breast cancer: results from the neoadjuvant part of the WSG-ADAPT-HR+/HER2- trial.

BACKGROUND: In high-risk hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC), nanoparticle albumin-bound (nab)-paclitaxel showed promising efficacy versus solvent-based (sb)-paclitaxel in neoadjuvant trials; however, optimal patient and therapy selection remains a topic of ongoing research. Here, we investigate the potential of Oncotype DX® recurrence score (RS) and endocrine therapy (ET) response (low post-endocrine Ki67) for therapy selection. PATIENTS AND METHODS: Within the WSG-ADAPT trial (NCT01779206), high-risk HR+/HER2- EBC patients were randomized to (neo)adjuvant 4× sb-paclitaxel 175 mg/m2 q2w or 8× nab-paclitaxel 125 mg/m2 q1w, followed by 4× epirubicin + cyclophosphamide (90 mg + 600 mg) q2w; inclusion criteria: (i) cN0-1, RS 12-25, and post-ET Ki67 >10%; (ii) cN0-1 with RS >25. Patients with cN2-3 or (G3, baseline Ki67 ≥40%, and tumor size >1 cm) were allowed to be included without RS and/or ET response testing. Associations of key factors with pathological complete response (pCR) (primary) and survival (secondary) endpoints were analyzed using statistical mediation and moderation models. RESULTS: Eight hundred and sixty-four patients received neoadjuvant nab-paclitaxel (n= 437) or sb-paclitaxel (n = 427); nab-paclitaxel was superior for pCR (20.8% versus 12.9%, P = 0.002). pCR was higher for RS >25 versus RS ≤25 (16.0% versus 8.4%, P = 0.021) and for ET non-response versus ET response (15.1% versus 6.0%, P = 0.027); no factors were predictive for the relative efficacy of nab-paclitaxel versus sb-paclitaxel. Patients with pCR had longer distant disease-free survival [dDFS; hazard ratio 0.42, 95% confidence interval (CI) 0.20-0.91, P = 0.024]. Despite favorable prognostic association of RS >25 versus RS ≤25 with pCR (odds ratio 3.11, 95% CI 1.71-5.63, P ≤ 0.001), higher RS was unfavorably associated with dDFS (hazard ratio 1.03, 95% CI 1.01-1.05, P = 0.010). CONCLUSIONS: In high-risk HR+/HER2- EBC, neoadjuvant nab-paclitaxel q1w appears superior to sb-paclitaxel q2w regarding pCR. Combining RS and ET response assessment appears to select patients with highest pCR rates. The disadvantage of higher RS for dDFS is reduced in patients with pCR. These are the first results from a large neoadjuvant randomized trial supporting the use of RS to help select patients for neoadjuvant chemotherapy in high-risk HR+/HER2- EBC.

[Regression of idiopathic epiretinal membrane-Case report and consideration of the possible mechanism]. / Regression einer idiopathischen epiretinalen Gliose ­ Kasuistik und Überlegungen zum Mechanismus.

In the presence of a symptomatic epiretinal gliosis, pars plana vitrectomy with membrane peeling to remove the membrane is usually indicated in clinical practice. According to common clinical experience, almost no independent regression of such an epiretinal membrane and thus healing of the pathology alone exists. Therefore, the unusual case of bilateral independent regression of idiopathic epiretinal gliosis and formation of a lamellar macular hole in a 73-year-old male patient is described. Considerations of the possible mechanism are presented based on the existing literature. These include separation of inflammatory versus noninflammatory membranes, possible separation of individual layers depending on the status of the posterior vitreous limiting membrane and also the possible action of proteolytic systems in the posterior vitreous region. Finally, the question arises, whether patients have to be informed about this fact before possible surgery.

[Real-life results of anti-VEGF treatment in fellow eyes with nAMD]. / Real-life-Ergebnisse der Anti-VEGF-Therapie bei nAMD der Partneraugen.

PURPOSE: Neovascular age-related macular degeneration (nAMD) often affects both eyes. This study compared real-life outcomes of the first affected eye (1st eye) and the last affected eye (2nd eye) after anti-vascular endothelial growth factor (anti-VEGF) treatment. MATERIAL AND METHODS: For this retrospective monocenter study 3217 eyes from 2793 patients with nAMD were identified, who received at least 3 anti-VEGF injections between 2006 and 2014 at the University Eye Hospital of Munich. Included in the study were patients with bilateral nAMD when the 1st and 2nd eyes were not previously treated and there was a strict adherence with continuous follow-up for at least 5 years. Corrected visual acuity, number of intravitreal injections and visits as well as central macular thickness were compared. RESULTS: A total of 72 eyes of 36 patients were included in this analysis. Before anti-VEGF therapy, the group of 2nd eyes showed significantly better mean visual acuity than the 1st eyes (p < 0.001). This difference in visual acuity between 1st and 2nd eyes was noted at all time points throughout the follow-up period (p < 0.05). The mean number of cumulative injections was higher in the group of 2nd eyes (p = 0.04) with a comparable number of visits between both groups. In more than half of all patients the 2nd eye became affected by nAMD within 12 months following treatment initiation of the 1st eye and the majority (83%) followed within 3 years. CONCLUSION: In unilateral nAMD, regular monitoring of the fellow eye is essential to avoid severe bilateral vision loss. Early diagnosis with rapid initiation of treatment can preserve visual acuity and quality of life.

International multicentre review of perioperative management and outcome for catecholamine-producing tumours.

BACKGROUND: Surgery for catecholamine-producing tumours can be complicated by intraoperative and postoperative haemodynamic instability. Several perioperative management strategies have emerged but none has been evaluated in randomized trials. To assess this issue, contemporary perioperative management and outcome data from 21 centres were collected. METHODS: Twenty-one centres contributed outcome data from patients who had surgery for phaeochromocytoma and paraganglioma between 2000 and 2017. The data included the number of patients with and without α-receptor blockade, surgical and anaesthetic techniques, complications and perioperative mortality. RESULTS: Across all centres, data were reported on 1860 patients with phaeochromocytoma or paraganglioma, of whom 343 underwent surgery without α-receptor blockade. The majority of operations (78·9 per cent) were performed using minimally invasive techniques, including 16·1 per cent adrenal cortex-sparing procedures. The cardiovascular complication rate was 5·0 per cent overall: 5·9 per cent (90 of 1517) in patients with preoperative α-receptor blockade and 0·9 per cent (3 of 343) among patients without α-receptor blockade. The mortality rate was 0·5 per cent overall (9 of 1860): 0·5 per cent (8 of 517) in pretreated and 0·3 per cent (1 of 343) in non-pretreated patients. CONCLUSION: There is substantial variability in the perioperative management of catecholamine-producing tumours, yet the overall complication rate is low. Further studies are needed to better define the optimal management approach, and reappraisal of international perioperative guidelines appears desirable.

ANTECEDENTES: La cirugía de los tumores productores de catecolaminas puede complicarse por la inestabilidad hemodinámica intraoperatoria y postoperatoria. Se han propuesto distintas estrategias de manejo perioperatorio, pero ninguna ha sido evaluada en ensayos aleatorizados. Para evaluar este tema, se han recogido los datos de los resultados y del manejo perioperatorio contemporáneo de 21 centros. MÉTODOS: Veintiún centros aportaron datos de los resultados de los pacientes operados por feocromocitoma y paraganglioma entre 2000-2017. Los datos incluyeron el número de pacientes con y sin bloqueo del receptor α, las técnicas quirúrgicas y anestésicas, las complicaciones y la mortalidad perioperatoria. RESULTADOS: Los centros en su conjunto aportaron datos de 1.860 pacientes con feocromocitoma y paraganglioma, de los cuales 343 pacientes fueron intervenidos sin bloqueo del receptor α. La gran mayoría (79%) de las cirugías se realizaron utilizando técnicas mínimamente invasivas, incluido un 17% de procedimientos con preservación de la corteza suprarrenal. La tasa de complicaciones cardiovasculares fue de 5,0% en total; 5,9% (90/1517) en pacientes con bloqueo preoperatorio de los receptores α y 0,9% (3/343) en pacientes no pretratados. La mortalidad global fue del 0,5% (9/1860); 0,5% (8/1517) en pacientes pretratados y 0,3% (1/343) en pacientes no tratados previamente. CONCLUSIÓN: Existe una variabilidad sustancial en el manejo perioperatorio de los tumores productores de catecolaminas, aunque la tasa global de complicaciones es baja. Este estudio brinda la oportunidad para efectuar comparaciones sistemáticas entre estrategias de prácticas terapéuticas variables. Se necesitan más estudios para definir mejor el enfoque de manejo óptimo y parece conveniente volver a evaluar las guías internacionales perioperatorias.

[Indications and surgical approach for lamellar macular holes and pseudoholes]. / Indikation und chirurgisches Vorgehen bei Makulaschichtforamen und Pseudoforamen.

BACKGROUND: This article presents a discussion on the indications for surgical interventions of lamellar macular holes and pseudoholes. OBJECTIVE: What are the criteria for deciding on the surgical intervention for lamellar macular holes and pseudoholes? MATERIAL AND METHODS: The article is based on a literature search in PubMed RESULTS: Lamellar macular holes and pseudoholes are subdivided into degenerative and tractive alterations. Both entities are associated with relatively specific morphological and functional criteria, which correlate with the expected functional and morphological results of the surgical intervention. Patients with pseudoholes therefore profit more from a surgical intervention because alterations to the outer retina are less pronounced in these cases. CONCLUSION: The indications for surgery of lamellar macular holes and pseudoholes are established by the type of lamellar defect and the morphological and functional alterations associated with this condition.

Moraxella catarrhalis induces CEACAM3-Syk-CARD9-dependent activation of human granulocytes.

The human restricted pathogen Moraxella catarrhalis is an important causal agent for exacerbations in chronic obstructive lung disease in adults. In such patients, increased numbers of granulocytes are present in the airways, which correlate with bacteria-induced exacerbations and severity of the disease. Our study investigated whether the interaction of M. catarrhalis with the human granulocyte-specific carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-3 is linked to NF-κB activation, resulting in chemokine production. Granulocytes from healthy donors and NB4 cells were infected with M. catarrhalis in the presence of different inhibitors, blocking antibodies and siRNA. The supernatants were analysed by enzyme-linked immunosorbent assay for chemokines. NF-κB activation was determined using a luciferase reporter gene assay and chromatin-immunoprecipitation. We found evidence that the specific engagement of CEACAM3 by M. catarrhalis ubiquitous surface protein A1 (UspA1) results in the activation of pro-inflammatory events, such as degranulation of neutrophils, ROS production and chemokine secretion. The interaction of UspA1 with CEACAM3 induced the activation of the NF-κB pathway via Syk and the CARD9 pathway and was dependent on the phosphorylation of the CEACAM3 ITAM-like motif. These findings suggest that the CEACAM3 signalling in neutrophils is able to specifically modulate airway inflammation caused by infection with M. catarrhalis.

The West German Study Group Breast Cancer Intrinsic Subtype study: a prospective multicenter decision impact study utilizing the Prosigna assay for adjuvant treatment decision-making in estrogen-receptor-positive, HER2-negative early-stage breast cancer.

PURPOSE: The West German Study Group (WSG) Breast Cancer Intrinsic Subtype (BCIST) study was designed to assess the influence of Prosigna gene signature assay results on physicians' adjuvant treatment recommendations by determining the extent of change in pre-test treatment recommendations following assay results. Secondary objectives were to assess the influence of Prosigna results on physicians' confidence in their therapeutic recommendations and on patients' decisional conflict status, anxiety levels, and functional status. METHODS: This prospective, observational, decision impact study enrolled consecutive postmenopausal patients with estrogen-receptor (ER)-positive, HER2-negative, lymph-node-negative early-stage breast cancer in 11 centers in Germany. Physicians based their pre-test adjuvant treatment recommendations on standard clinico-pathological parameters. Tumor specimens were assayed using the Prosigna test in a WSG central pathology laboratory following manufacturer's guidelines. An independent pathology laboratory performed subsequent Prosigna assays on tumor sections to assess assay result concordance with the central laboratory. Physicians completed treatment confidence questionnaires prior to and after receiving Prosigna test results. Patients completed standardized questionnaires on decisional conflict, anxiety, and health status both before and after Prosigna testing. RESULTS: The present study population consisted predominantly of low-to-intermediate risk patients (N = 198). Prosigna had 29.3% discordance in intrinsic subtyping with local immunohistochemistry test results. After Prosigna test results, a change in the adjuvant therapy recommendation occurred in 36 (18.2%) patients; 22 (11.1%) patients switched from no chemotherapy to chemotherapy. After Prosigna test results, physicians expressed increased confidence in their prognostic assessment in 87.9% of patients, and increased confidence in their treatment recommendation in 89.4%. Patients reported improved anxiety and emotional/functional well-being after receiving Prosigna test results. CONCLUSIONS: Use of the Prosigna assay led to a change in 18.2% of adjuvant treatment decisions. Prosigna testing was associated with increased patient and physician confidence in treatment decisions, and with decreased patient anxiety and improved well-being. Any comparison of the therapeutic decision-making impacts of different genomic assays must account for potential confounding factors.

[Clinicopathological correlations at the vitreoretinal interface]. / Klinisch-pathologische Korrelationen an der vitreoretinalen Grenzfläche.

BACKGROUND: Clinicopathological studies of the vitreoretinal interface (VRI) improve our understanding of the pathogenesis of vitreal maculopathy, facilitate differential diagnoses and help to develop new treatment strategies. OBJECTIVE: The aim of the study was to provide a comprehensive overview on clinicopathological correlations of the VRI. METHODS: A semi-structured literature search was performed in the Medline and Embase databases for relevant original studies on clinicopathological correlations of vitreal maculopathy, in addition to the latest books and review articles. RESULTS: Age-related vitreous changes with persistent vitreomacular adhesions on the retinal surface promote cellular migration and proliferation onto the vitreal side of the internal limiting membrane (ILM), thereby cementing the vitreomacular adhesions and strengthening the traction forces on retinal layers. Cellular or fibrocellular proliferation at the vitreomacular interface can be seen in all vitreal maculopathies. Furthermore, vitreoschisis in the context of anomalous posterior vitreous detachment causes the presence of vitreous cortex collagen fibrils on the vitreal side of the ILM which is associated with epiretinal membrane formation. Glial cells, hyalocytes and myofibroblasts represent the major cell types in the epiretinal cell proliferation. Glial cells and hyalocytes are capable of transdifferentiation into myofibroblasts which possess strong contractive properties and are well known for the production of extracellular matrix components. CONCLUSION: Removing vitreomacular adhesions and vitreous cortex collagen fibrils from the retinal surface is most important for successful treatment. In cases with epiretinal cell proliferation, however, removal of the ILM during macular surgery is mandatory to avoid reproliferation and recurrence. Improving the detection of epiretinal cell proliferation and cell distribution in patient eyes by optical coherence tomography or by introduction of new technologies should be addressed in the future.

Association of metabolic syndrome and surgical factors with pulmonary adverse events, and longitudinal mortality in bariatric surgery.

BACKGROUND: Postoperative pulmonary complications (PPC) in bariatric surgery have not been well studied. Additionally, many bariatric patients suffer from the metabolic syndrome (MetS), contributing to surgical risk. We examined the incidence of PPC and MetS in a large national bariatric database. Furthermore, we analysed the relationships between morbidity, mortality, PPC, MetS, and several other comorbidities and also surgical factors. METHODS: The Bariatric Outcomes Longitudinal Database (BOLD™) is a registry that includes up to 365 day outcomes. We analysed data between January 2008 and October 2010. The PPC tracked included pneumonia, atelectasis, pleural effusion, pneumothorax, adult respiratory distress syndrome, and respiratory failure. A composite pulmonary adverse event (CPAE) included the occurrence of any of these. MetS was defined as the combination of hypertension, dyslipidaemia, and diabetes mellitus. The association of MetS and additional comorbibities, procedural data, and patient characteristics with CPAEs was examined with appropriate statistical tests. RESULTS: A total of 158 405 patients had a low incidence of PPC (0.91%) and a low mortality (0.6%) after bariatric surgery. MetS was prevalent in 12.7%, and was a significant risk factor for CPAE and mortality. Age, BMI, ASA physical status classification, surgical duration, procedure type, MetS (P<0.001), and additional comorbidities were significantly associated with CPAEs. CONCLUSIONS: The incidence of PPC was low after bariatric surgery. Increasing age, BMI, ASA status, MetS, obstructive sleep apnoea, asthma, congestive heart failure, surgical duration, and procedure type were independently significantly associated with PPC. Pulmonary complications and MetS were significantly associated with increased postoperative mortality.

A micro RNA-146a polymorphism is associated with coronary restenosis.

The association of the miRNA-146a polymorphism rs2910164 with atherosclerosis and restenosis was investigated. We found no association with atherosclerosis; however, we found a negative association for the G/C (P = 0.007) and a positive association for the C/C genotype with the risk of restenosis, which is the main drawback for cardiac surgery.

[Epiretinal gliosis]. / Epiretinale Gliose.

Epiretinal membranes represent avascular cellular proliferations on the retinal surface, preferentially in the area of the macula. Idiopathic, primary epiretinal membranes are a relatively common finding, especially in elderly people. Other secondary pathomechanisms include retinal tears, trauma, ophthalmic surgical procedures including retinal detachment surgery, laser coagulation and cryotherapy of the retina, or as a result of inflammatory diseases. Individual symptoms depend on the degree of cellular proliferation and associated tangential traction forces at the vitreoretinal interface resulting in surface wrinkling of the retina. Patients often complain of a reduction of visual acuity accompanied by metamorphopsia. A surgical intervention using transconjunctival pars plana vitrectomy and membrane peeling is indicated depending on the reduction of visual acuity and the severity of metamorphopsia if present.

Chromovitrectomy and the vitreoretinal interface.

It still remains unclear to which extent the presence and the amount of retinal debris seen in internal limiting membrane (ILM) specimens harvested during macular surgery for macular holes or epiretinal membranes are related to the procedure of ILM peeling itself or to modifications of the surgical technique, such as application of vital dyes for visualization of the ILM, or to pathological conditions with epiretinal membrane formation at the vitreoretinal interface. The presence of cellular fragments on the retinal side of the removed ILM appears to be of multifactorial origin, and additional causes besides dye application need to be considered. However, morphological studies with evaluation of vital dyes are still of relevance and provide additional insights into the ultrastructure of the vitreoretinal interface and its interaction with adjuvants used during macular surgery. Chromovitrectomy is an emerging field in vitreoretinal surgery. It is of importance to better understand the tissue-dye interactions, which not only alter the mechanical properties of the tissue being stained, but may also have an impact on the functional result postoperatively.

The volume and pH of residual pharyngeal fluid aspirated from the TaperGuard Evac™ Endotracheal Tube following elective surgery: a prospective pilot study.

BACKGROUND: Oropharyngeal suctioning prior to extubation aims to minimize postextubation tracheal soiling from remaining fluid. We investigated the amount and nature of any fluid remaining after such suctioning and contributing factors. METHODS: ASA I - III patients undergoing elective surgery under general anesthesia with endotracheal intubation participated in this prospective observational pilot study. Following oropharyngeal suctioning immediately prior to extubation, a dedicated port of the endotracheal tube (TaperGuard Evac™ Endotracheal Tube) was aspirated. The amount and pH of residual fluid was recorded. Data collection included age, sex, body mass index, comorbidities, ASA status, procedure type and duration. The Chi-Square, Wilcoxon Rank-Sum, t-tests, and univariate regression analysis were used as appropriate. RESULTS: Ninety-eight patients completed the study. The mean aspirated volume in 38 (38.8%) patients was 0.9 ± 1.3 mL and sixty patients (61.2%) had no aspirate. A body mass index of ≥ 30 kg/m2 was associated with the presence of fluid (P=0.03), and a higher volume (P=0.03). The fluid pH was 7 ± 0.81 (mean ± SD). A duration of surgery ≥ 120 minutes predicted a lower pH. CONCLUSION: The prevalence and amount of residual fluid after oropharyngeal suctioning was low and likely clinically insignificant. A higher body mass index was associated with a higher incidence and volume of residual fluid. Longer procedure duration determined a slightly lower pH, with a mildly acidic pH range. The possibility of a lower fluid pH after prolonged surgery contributing to postoperative sore throat via mucosal irritation warrants investigation.

[Laryngeal and pharyngeal actinomycosis]. / Aktinomykose im Bereich von Pharynx und Larynx.

Cervicofacial actinomycosis is an uncommon infection and in most cases odontogenic in origin. Pharyngeal and/or laryngeal lesions, usually occurring secondary to mucosal trauma, are very rare and may mimic a malignant tumor. In such cases, which represent less than 1% of all cases, the differential diagnosis with upper aerodigestive tract malignancy remains challenging. We report a case of actinomycosis in a 56-year-old male patient who presented with an extensive, centrally necrotic mass in the oropharynx, hypopharynx and larynx region suspected to be a tumor. The lesion was diagnosed 6 months following accidental ingestion of an ear of corn and ultimately proved to be cervicofacial actinomycosis. The clinical and pathological features and current aspects of the diagnosis and treatment of cervicofacial actinomycosis are discussed.

[Alkylphosphocholines inhibit lens epithelial cell proliferation and attachment]. / Alkylphosphocholine hemmen die Proliferation und Anhaftung von Linsenepithelzellen.

BACKGROUND: Posterior capsule opacification (PCO) is one of the major concerns in modern cataract surgery. Ten years after successful surgery, Nd:YAG capsulotomy is required in up to 42% of patients with an acrylic sharp-edged intraocular lens (IOL). Some accommodative and multifocal IOLs display even higher capsulotomy rates. Pharmacologic prophylaxis with alkylphosphocholines (APCs) could be a novel option in PCO prevention. METHODS: The human lens epithelial cell line HLE-B3 served as an in-vitro model. After incubation with APCs in different concentrations (0.01, 0.1, and 1 mM), the trypan blue exclusion assay and the live/dead test were performed at serum concentrations of only 5%. Cell proliferation was assessed with the MTT test. Evaluation of cell attachment was done with fibronectin- and laminin-coated wells. RESULTS: APCs can inhibit the proliferation of human lens epithelial cells in the presence of only 5% serum in a dose-dependent manner. Proliferation inhibition of 60% and attachment inhibition of about 50% were reached at concentrations of 0.1 µM. CONCLUSION: APCs inhibit proliferation and attachment of human lens epithelial cells in nontoxic concentrations in vitro. The substance can be applied topically, and an intraoperative application for pharmacologic PCO prophylaxis is feasible.

Prevention of biofilm growth on man-made surfaces: evaluation of antialgal activity of two biocides and photocatalytic nanoparticles.

As algal growth on man-made surfaces impacts their appearance, biocides and surfaces with self-cleaning properties are widely used in the building and paint industries. The objective of this study was to evaluate the antialgal activity of two biocides (triazine and isothiazoline) and photocatalytic nanoparticles of zinc oxide (20-60 nm). An aeroterrestrial green, microalgal strain of the genus Stichococcus was chosen as the test organism. By comparing a set of different structural and physiological performance parameters, lethal and also sublethal (chronic) effects were determined. Even though the herbicide triazine effectively inhibited growth (EC50 = 1.6 micromol l(-1)) and photosynthetic performance, structural properties (eg membrane integrity) were unaffected at the EC100 (250 micromol l(-1)), hence this herbicide did not kill the algal cells. In contrast, and due to their multiple modes of action, isothiazoline and the photocatalytic nanoparticles (the latter activated with low UV radiation) severely impacted all performance and structural parameters.

Association of the toll-like receptor 2 A-16934T promoter polymorphism with severe atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial pathogenesis and increasing incidence in the Western world. A genetically determined defective function of pattern recognition receptors such as toll-like receptors (TLRs) has been proposed as a candidate mechanism in the pathogenesis of AD. AIM: To study the impact of genetic predisposition of five genes encoding for pattern recognition-related molecules for the phenotype of AD. METHODS: We examined nine different single-nucleotide polymorphism (SNP) frequencies in the genes encoding TLR1, -2, -4, -9 and the adapter molecule TIRAP by PCR with subsequent melting curve analysis in a case/control cohort of 136 adult AD patients and 129 age and gender matched non-atopic, healthy individuals. TLR2-expression and -function in cells from genotyped individuals were analysed. RESULTS: For the SNPs examined, similar genotype frequencies were found in both groups. In a subgroup of patients suffering from severe AD (SCORAD >50), a significantly increased representation of the A-allele in position -16934 of the tlr2 gene was present (P = 0.004). Constitutive tlr2 mRNA expression in peripheral monocytes was independent of this tlr2 promoter SNP. Stimulation assays indicated that IL-6, but not TNF-alpha secretion following TLR2 stimulation is reduced in homozygous tlr2-16934-A allele carriers. CONCLUSION: These data indicate that TLR2 is relevant for the phenotype of severe AD in adults.

An in vivo evaluation of Brilliant Blue G in animals and humans.

BACKGROUND/AIMS: To evaluate the retinal toxicity of Brilliant Blue G (BBG) following intravitreal injection in rat eyes and examine the biocompatibility and the staining properties in humans. METHODS: BBG was injected into the 11 rat eyes to evaluate toxic effects with balanced salt solution (BSS) serving as control. Retinal toxicity was assessed by retinal ganglion cell (RGC) counts and by light microscopy 7 days later. In addition, BBG was applied during vitrectomy for macular hole (MH) (n = 15) or epiretinal membranes (ERM) (n = 3) in a prospective, non-comparative consecutive series of patients. Before and after surgery, all patients underwent a complete clinical examination including measurement of best corrected visual acuity (VA) and intraocular pressure, perimetry, fundus photography and optical coherence tomography. Patients were seen 1 day before surgery and then in approximately four weeks intervals. RESULTS: No significant reduction in RGC numbers and no morphological alterations were noted. A sufficient staining of the internal limiting membrane (ILM) was seen in patients with MH, while the staining pattern in ERM cases was patchy, indicating that parts of the ILM were peeled off along with the ERM in a variable extent. All MHs could be closed successfully. VA improved in 10 eyes (56%; 8/15 MH patients, 2/3 ERM patients), was unchanged in four eyes (22%; all MH patients) and was reduced in four eyes (22%; 3/15 MH, 1/3 ERM). No toxic effects attributable to the dye were noted during patient follow-up. The ultrastructure of tissue harvested during surgery was unremarkable. CONCLUSION: Brilliant Blue provides a sufficient and selective staining of the ILM. No retinal toxicity or adverse effects related to the dye were observed in animal and human studies. The long-term safety of this novel dye will have to be evaluated in larger patient series and a longer follow-up.

[The primary objective in macular hole surgery. Ultrastructural features of the vitreomacular interface]. / Operative Zielvorgabe in der Makulaforamenchirurgie. Neue Aspekte zur Feinstruktur der vitreomakulären Grenzfläche.

We compared the ultrastructure of the inner limiting membrane (ILM) and epiretinal tissue in closed and non-closed, idiopathic macular holes (MH). Peeling of ILM and epimacular tissue during vitrectomy was successfully performed on 77 eyes with stage III MH and on 19 eyes with stage IV MH. In 16 additional eyes with non-closed MH, we performed a second vitrectomy with extended ILM removal. The specimens were processed for transmission electron microscopy. Fibrocellular proliferation at the vitreal side of the ILM was found in 57% of MH that were closed by one operation, and in 100% of non-closed MH. Mono- and multilayered cellular membranes as well as native vitreous collagen at the ILM were significantly more frequent in eyes with stage IV MH than in eyes with stage III MH. In non-closed MH, cellular proliferation was mostly seen as irregular cell accumulation, and masses of newly formed collagen were found. Since ILM remnants and collagen represent a stimulus for the early formation of tangential traction preventing successful MH closure, it appears mandatory to create a complete vitreoretinal separation and to remove the ILM and collagen thoroughly during MH surgery.