Frequently assessed and used prognostic factors for outcome after macular hole surgery: which is better?

BACKGROUND: The aim of this retrospective study was to evaluate commonly used clinical and OCT-morphological parameters, including perifoveal pseudocysts, as prognostic factors for postoperative outcome after macular hole surgery in a retinal referral clinic in North Rhine-Westphalia, Germany. METHODS AND MATERIAL: This was a retrospective analysis of all patients who underwent surgery because of idiopathic MH between 2011 and 2017 in Augenklinik Tausendfensterhaus, Duisburg, Germany. Statistical evaluation of clinical and OCT-based parameters, including the areas of intraretinal pseudocysts, was conducted. The main statistical outcomes were surgical success and visual acuity. Only parameters with a highly significant correlation to the outcome parameters (postoperative visual acuity (VA); surgical success) in univariate analysis were entered in linear and logistic regression analyses. RESULTS: A total of 189 eyes of 178 patients (71.4% female; mean age 67.5 ± 8.2 a) who underwent surgery because of MH were included. The overall closure rate was 86.8%. The mean best corrected VA increased from 0.7 ± 0.3 logMAR before surgery to 0.5 ± 0.3 logMAR (p < 0.0001). While several clinical and OCT-based parameters as well as calculated indices showed a significant correlation with the outcome measures, the regression analysis showed that the minimum linear diameter was the only parameter that both predicted surgical success (p = 0.015) and was correlated with postoperative VA (p < 0.001). CONCLUSION: The minimum linear diameter serves as an easily assessed prognostic factor with the best predictive properties. This result is of great importance for clinical practice, as it simplifies the postsurgical prognosis.

Helminth species-specific effects on IFN-γ producing T cells during active and latent tuberculosis.

BACKGROUND: Interferon-γ (IFN-γ) is a key cytokine inducing protective immune responses during tuberculosis (TB) infection. Helminth-induced immune responses may affect IFN-γ production by T cells, although its connection with disease severity and immune recovery during treatment is unexplored. We investigated the species-specific effect of helminths on the IFN-γ production by T cells in relation to disease severity during active and latent TB infection (LTBI). METHODS: In this study, 69 active pulmonary TB patients (PTB), 28 with LTBI and 66 healthy controls were included. Active TB was diagnosed using GenXpert MTB/RIF while QuantiFERON test (QFT) was used for the screening of healthy community controls (CCs) and for the diagnosis of LTBI. Helminth infection was identified by routine diagnosis whereas clinical disease severity was evaluated by the TB score. Intracellular IFN-γ production of T cells in stimulated peripheral blood mononuclear cells (PBMCs) was analyzed by flow cytometry using TB antigens (PPD), the polyclonal T cell activator staphylococcal enterotoxin B (SEB), or medium as unstimulated control. RESULTS: Helminth infected CCs and LTBI subjects showed a significant reduction of IFN-γ+ CD4+ T cells by PPD-stimulation compared to non-helminth infected control groups. The significant reduction in the frequency of IFN-γ+ T cells in both latent and active PTB patients following SEB stimulation was mostly attributed to Schistosoma mansoni infection, whereas Ascaris lumbricoides, Schistosoma mansoni, and hookworm infection contributed equally in CCs. Following anti-helminthic and anti-TB treatment for 2 months, the frequency of IFN-γ+ CD4 T cells in helminth coinfected PTB was restored to levels of helminth negative PTB before treatment. Helminth coinfected PTB patients with an intermediate and severe clinical course had reduced capacity for production of IFN-γ+ T cells compared to the corresponding non-helminth infected PTB. CONCLUSION: We found a reduction in IFN-γ producing T cells by helminth coinfection which was restored following anti-helminthic treatment. This reduction was helminth species-dependent in an exploratory sub-analysis and correlated to increased disease severity.

Age-dependent expression of DNMT1 and DNMT3B in PBMCs from a large European population enrolled in the MARK-AGE study.

Aging is associated with alterations in the content and patterns of DNA methylation virtually throughout the entire human lifespan. Reasons for these variations are not well understood. However, several lines of evidence suggest that the epigenetic instability in aging may be traced back to the alteration of the expression of DNA methyltransferases. Here, the association of the expression of DNA methyltransferases DNMT1 and DNMT3B with age has been analysed in the context of the MARK-AGE study, a large-scale cross-sectional study of the European general population. Using peripheral blood mononuclear cells, we assessed the variation of DNMT1 and DNMT3B gene expression in more than two thousand age-stratified women and men (35-75 years) recruited across eight European countries. Significant age-related changes were detected for both transcripts. The level of DNMT1 gradually dropped with aging but this was only observed up to the age of 64 years. By contrast, the expression of DNMT3B decreased linearly with increasing age and this association was particularly evident in females. We next attempted to trace the age-related changes of both transcripts to the influence of different variables that have an impact on changes of their expression in the population, including demographics, dietary and health habits, and clinical parameters. Our results indicate that age affects the expression of DNMT1 and DNMT3B as an almost independent variable in respect of all other variables evaluated.

A novel vascular sealing device for closure of percutaneous arterial access sites.

The purpose of this study was to investigate the safety and efficacy of a novel vascular sealing device that incorporates a unique low-profile balloon-positioning catheter and a procoagulant delivered after diagnostic cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA) procedures. Current management of the vascular access site after percutaneous interventions is associated with patient discomfort and complications. Based on previously reported successful results in canine models, we proceeded with this first human feasibility and safety study. Immediately after an invasive procedure, the sealing device was successfully deployed at the femoral arterial access site in 24 of 24 procedures (diagnostic 19, PTCA 5). All patients were followed up at 1 month with clinical assessment, ankle-brachial index measurement, and Doppler ultrasound. Successful hemostasis was achieved in all patients. The activated clotting time before sealing device deployment was 125.5 +/- 22.2 and 267.8 +/- 60.0 seconds for diagnostic and PTCA patients, respectively. The time to hemostasis was 2.5 +/- 0.9 minutes for diagnostic and 6.0 +/- 2.2 minutes for PTCA patients. No major complications were observed. Coagulation markers (fibrinogen, D-dimer, thrombin-antithrombin-3 complex, and prothrombin fragment 1 and 2) measured before and after sealing device deployment did not reveal excessive intravascular thrombin generation or other coagulopathy. This novel vascular sealing device successfully achieves safe and effective vascular access site hemostasis immediately after cardiac catheterization and PTCA. These promising first human results will need to be confirmed by a multicenter randomized trial.

[Accidental occlusion of the common femoral artery after Angio-Seal-application]. / Akzidenteller Verschluss einer A. femoralis communis nach Angio-Seal-Applikation.

Removal of the arterial sheath immediately after PTCA is desirable for patients, reduces the medical staff's workload, and may decrease hospital costs due to a shortened length of stay. Although the safety and efficacy of the hemostatic systems used especially for the above purpose have been sufficiently documented, inadvertent intraluminal vascular occlusion is theoretically possible. While partial or complete arterial occlusion in conjunction with the VasoSeal collagen prototype device has been previously reported, similar complications occurring with the Angio-Seal device were not published. In this report, we describe a 54-year old female patient (height: 150 cm, weight: 42.5 kg) who was transferred for PTCA following an acute anterior wall myocardial infarction. Immediately after PTCA, the Angio-Seal device was deployed utilizing standard technique. No difficulties were encountered during device deployment, however, immediately following device placement active arterial bleeding occurred. Due to the inadequacy of hemostasis, heparin was reversed with protamine to avoid further hemorrhagic complications. Following this, the desired hemostasis quickly occurred, but the patient soon complained about symptoms suggestive of an acute occlusion of the right femoral artery. Unsatisfactory attempts at lysis resulted in the patient being transferred to vascular surgery. The complete Angio-Seal system (anchor including collagen) was located intravascularly, and removed during surgery. This case report demonstrates that even an experienced examiner can inadvertently deploy the Angio-Seal completely intraarterially. In addition to the known contraindication, "peripheral arterial occlusive disease", we recommend that the Angio-Seal device not be utilized in patients of small physical size.

A fluorescent substrate of transglutaminase for detection and characterization of glutamine acceptor compounds.

A fluorescent dipeptide was designed to discover glutamine acceptor proteins of transglutaminase. Starting materials for synthesis were the commercially available compounds carbobenzoxy-L-glutaminylglycine (CBZ-Gln-Gly) and monodansylcadaverine (C-DNS) which were coupled to obtain CBZ-Gln-Gly-C-DNS 1 [1-N-(carbobenzoxy-L-glutaminylglycyl)-5-N- (5'-N', N'-dimethylamino-1'-naphthalenesulfonyl)- diamidopentane]. The glutamine peptide is a substrate of bacterial transglutaminase from Streptoverticillium mobaraense as well as of the guinea pig liver enzyme. This could be shown by incorporating 1 into alpha s1-casein resulting in a significant increase in fluorescence intensity and a concomitant inhibition of cross-linking reaction. Additionally, dipeptide 1 is a useful tool to characterize the specificity of transglutaminase toward small primary amines. We established a sensitive HPLC assay and determined the kinetic parameters of several alkylamines. Hydrolysis of 1 is suppressed in the presence of the nucleophiles as it could be demonstrated with different concentrations of butylamine in semiquantitative studies. Together with labeled primary amines, reagent 1 seems to be a particularly suitable tool for examining acceptor-donor relationships of transglutaminase substrates.