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Objectives: This study investigates the outcome of short implants additionally placed with longer implants to support a maxillary overdenture. Materials and methods: Twelve patients received six implants to support a maxillary overdenture. Only one patient still had two molars in the maxilla, while the others had no remaining teeth. The status of the opposing arch was diverse. The distal implant in each quadrant was 6 mm in height (S) and the middle implants ranged between 10 and 14 mm (L). All implants were placed following a one-stage procedure and early loaded (6 weeks). Clinical and radiological parameters were assessed 6, 12 and 24 months after loading. Results: One short implant failed 2 weeks after surgery, probably due to early mobilization by the provisional prosthesis. The mean bone loss on the rough part of the implant was 0.7 mm (S) vs. 1.3 mm (L) during the first year and 0.3 mm (S) vs. 0.2 mm (L) during the second year after loading. The mean implant stability quotient values were 67 (S) vs. 70 (L) at placement and 75 (S) vs. 78 (L) after 1 year. At the 2-year follow- up, all prostheses were still stable and comfortable. Conclusion: An overdenture on six implants, of which two have a reduced length, might represent a successful treatment option. No significant difference could be found between both implant lengths at 2 years' follow-up. However, bone loss with short implants may increase the likelihood of failure. [ABSTRACT FROM AUTHOR]

PurposeTo compare 1-year functional and anatomic outcomes of intravitreal bevacizumab (IVB) and photodynamic therapy plus intravitreal triamcinolone (PDT+IVTA) combination in patients with neovascular age-related macular degeneration (AMD).MethodsIn this prospective, randomised, controlled clinical trial, 28 patients were included. All patients were randomised 1 : 1 to 0.04 ml/1 mg of IVB or PDT plus same day 0.1 ml/4 mg IVTA (PDT+IVTA). Follow-up examinations were performed in monthly intervals in IVB group and every 3 months in PDT+IVTA group. Main outcomes were change in mean visual acuity (VA), mean central retinal thickness (CRT) and the mean number of treatments.ResultsAt month 12, mean VA improved to a 1.5-line gain in IVB group, and lost three letters in PDT+IVTA group (P=0.02). Mean CRT was reduced from 357 μm at baseline to 244 μm at month 12 in IVB group and from 326 μm to 254 μm, respectively, in PDT+IVTA group (P=0.8). The mean number of treatments was 6.8 in the IVB group vs1.9 in the PDT+IVTA group. No significant local or systemic safety concerns were detected during follow-up time.ConclusionsPatients treated with IVB showed a significant better VA outcome compared with the PDT+IVTA group despite the fact that both modalities showed equal potency in reducing CRT during a 12-month period. [ABSTRACT FROM AUTHOR]

Objective: To evaluate efficacy and safety of intravitreal bevacizumab (Avastin) in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Methods: Twenty-eight consecutive patients (28 patients, 29 eyes, 8 CRVO, 21 BRVO) were enrolled in the study. Three intravitreal injections of 1 mg bevacizumab (0.04 ml) were administered at 4-week intervals; further retreatment was based on optical coherence tomography (OCT) findings. Follow-up examinations were done at days 1, 7 and 28 and at monthly intervals thereafter. Results: Mean baseline central retinal thickness (CRT) in OCT was 558 µm (range 353-928 µm) and mean BCVA was 20/100. One day after the first injection, CRT significantly decreased to 401 µm (p<0.01). Three injections reduced macular oedema to 328 µm CRT (p<0.01) and improved BCVA to 20/50 (p<0.01). At 6 months, CRT was 382 µm (p<0.01), and BCVA was stable at 20/50-2 (p<0.01), FA showed no evidence of increased avascular zones. Conclusion: Intravitreal injections of bevacizumab appear to be a safe and effective therapy in the treatment of macular oedema secondary to retinal vein occlusion. [ABSTRACT FROM AUTHOR]

Aims: To compare functional and anatomical outcomes of intravitreal bevacizumab (Avastin) and verteporfin (photodynamic) therapy (PDT) combined with intravitreal triamcinolone (IVTA) in patients with neovascular age- related macular degeneration (AMD). Methods: Twenty-eight patients with neovascular AMD were enrolled in a prospective, randomised, controlled clinical trial. All patients randomly assigned to 1 mg intravitreal bevacizumab (0.04 ml) received three initial treatments at 4-week intervals. In further follow-up retreatment was based on optical coherence tomography (OCT). Patients randomly assigned to standard PDT received a same-day intravitreal injection of 4 mg triamcinolone (Kenalog). Retreatment was based on fluorescein angiography at 3-month intervals. Functional and anatomical results were evaluated using the Early Treatment Diabetic Retinopathy Study protocol vision charts, fluorescein angiography and OCT. Results: In the bevacizumab-treated group mean visual acuity (VA) improved to a 2.2 line gain at 6 months follow-up. Eyes treated in the POT plus IVTA group had a stable mean VA at month 6 compared with baseline. There was a statistically significant difference (p = 0.03, analysis of variance (ANOVA)) between both groups as early as one day after initial treatment. The reduction in central retinal thickness (CAT) showed no significant difference between both groups (p = 0.3, ANOVA(. Mean CAT was reduced from 357 jim at baseline to 239 jim at month 6 in bevacizumab-treated patients and from 326 jim to 222 jim, respectively, in POT plus IVTA- treated patients. No significant local or systemic safety concerns were detected up to month 6. Conclusion: Intravitreal bevacizumab showed promising 6-month results in patients with neovascular AMD. Functional outcomes appear not only to be dependent on a reduction in CAT but also on the treatment modality used. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate pathological changes of retinal pigment epithelium (RPE) by polarisation-sensitive optical coherence tomography (PS-OCT). Methods: Forty-four eyes (22 patients) with significant pathologies of the APE were evaluated using PS-OCT. A transversal scanning time domain OCT system was used for two-dimensional cross-sectional imaging of retinal polarisation properties. Results: The RPE scrambles the polarisation state of backscattered light (ie, acts as a depolarising layer), while the polarisation state of transmitted light is maintained. In patients with APE pathologies irregularity, elevation, thickening or absence of the APE is readily visualised by exploiting the depolarisation information. Polarisation scrambling in the sensory retina can be found in cases with advanced dry age-related macular degeneration. Sclera and fibrosis show characteristic birefringence in PS-OCT. Conclusion: PS-OCT allows tissue identification based on polarisation scrambling and birefringence, providing additional information on APE pathologies. It is a promising new tool for diagnosis, disease follow-up and evaluation of new treatment strategies. [ABSTRACT FROM AUTHOR]

Defines the respective role of the sites of glyceraldehyde 3-phosphate (Ps site) and inorganic phosphate (Pi site) during the successive steps of catalysis. Steady-state kinetics; Consequences of the mutations on the overall steps leading to acylenzyme formation; Rate constant of dihydronicotamide adenine dinucleotide (NADH) release.

2006; 16 (7): 916 - 28. 16 Radakovic R, Abrahams S. Developing a new apathy measurement scale: Dimensional Apathy Scale, Psychiatry Res. 2014; 219 (3): 658 - 63. 17 Huynh W, Ahmed R, Mahoney CJ, et al. Measurement of Social Cognition in Amyotrophic Lateral Sclerosis: A Population Based Study. 7 Girardi A, MacPherson SE, Abrahams S, Deficits in emotional and social cognition in amyotrophic lateral sclerosis, Neuropsychology. [Extracted from the article]

The author reflects on the safety and effectiveness of bevacizumab (Avastin). The author comments that the drug has the concern for an increased risk for thromboembolic events, which was found from 1.9% to 4.4%. The author also noted that the intravitreal injection of the drug is harmful to the intraocular components and has the potential for systemic adverse effects.

Objective: To evaluate verteporfin and same-day ranibizumab on retina, choroid, vasculature, choroidal neovascularisation (CNV) and visual function. Methods: Eleven patients with occult or predominantly classic subfoveal CNV secondary to age-related macular degeneration received verteporfin and four monthly intravitreal ranibizumab injections. Eyes were examined using fluorescein angiography (FA) and indocyanine green angiography (ICGA), optical coherence tomography (OCT), visual acuity (VA) and microperimetry. Results: Over 9 months, seven patients gained three to 24 letters and one had unchanged VA. Three patients lost eight to 24 letters due to recurrence and received another verteporfin treatment at month 6. Median retinal sensitivity of the central 4° of the macula increased from 0.9 (SD 2.3) dB (baseline) to 5.2 (1.8) dB (only baseline verteporfin) and 4.1 (4.5) dB (second verteporfin treat- ment) at study end. OCT showed sub- and intraretinal leakage increased with verteporfin, but resolved after 2 weeks. After combination treatment, CNV was completely occluded on FA within 1 week. ICGA showed non-perfusion of small/medium choroidal vessels. Recovery of choroidal perfusion began after 1 month, but remained impaired throughout follow-up. Conclusion: Verteporfin/ranibizumab was associated with CNV occlusion, reduced oedema, improved visual function and retinal sensitivity. The clinical significance of these findings requires further investigation. [ABSTRACT FROM AUTHOR]

Background: To compare early treatment effect of reduced fluence versus standard photodynamic therapy (rPDT, sPOT, respectively) in combination with intravitreal triamcinolone (IVTA) in neovascular age-related macular degeneration. Methods: Forty patients received either sPDT (group A, n = 20) or rPDT (group B, n = 20) each followed by same-day 4 mg IVTA. Patients were examined at baseline, day 1, week 1, 4 and 12. Main outcomes were visual acuity, central retinal thickness (CAT), choroidal perfusion and macular sensitivity (MS). Results: Baseline characteristics were well balanced in both groups (p>0.05(. At week 12, patients in group A had a mean loss of -3.7 letters compared with a gain of 3.4 letters in group B (p = 0.04, between both groups). Both treatment groups showed a similar course regarding CRT as well as MS (p>0.05). In 70% (14/20) of group A and 15% (3/20) of group B, a choroidal hypoperfusion in the area of treatment was observed after treatment (p<0.001). In 70% of group A and 55% of group B, a repeat treatment was indicated at week 12 (p = 0.55). Conclusions: At month 3, the rPDT+IVTA group showed a significantly better visual outcome, less alteration of the choroid and a trend for lower recurrence rate than the sPDT+IVTA group. Further follow-up of this study will provide information on long-term functional results and treatment durability. [ABSTRACT FROM AUTHOR]

Background We analyzed whether co-occurring mutations influence the outcome of systemic therapy in ALK -rearranged non-small-cell lung cancer (NSCLC). Patients and methods ALK -rearranged stage IIIB/IV NSCLC patients were analyzed with next-generation sequencing and fluorescence in situ hybridization analyses on a centralized diagnostic platform. Median progression-free survival (PFS) and overall survival (OS) were determined in the total cohort and in treatment-related sub-cohorts. Cox regression analyses were carried out to exclude confounders. Results Among 216 patients with ALK -rearranged NSCLC, the frequency of pathogenic TP53 mutations was 23.8%, while other co-occurring mutations were rare events. In ALK/TP53 co-mutated patients, median PFS and OS were significantly lower compared with TP53 wildtype patients [PFS 3.9 months (95% CI: 2.4–5.6) versus 10.3 months (95% CI: 8.6–12.0), P < 0.001; OS 15.0 months (95% CI: 5.0–24.9) versus 50.0 months (95% CI: 22.9–77.1), P = 0.002]. This difference was confirmed in all treatment-related subgroups including chemotherapy only [PFS first-line chemotherapy 2.6 months (95% CI: 1.3–4.1) versus 6.2 months (95% CI: 1.8–10.5), P = 0.021; OS 2.0 months (95% CI: 0.0–4.6) versus 9.0 months (95% CI: 6.1–11.9), P = 0.035], crizotinib plus chemotherapy [PFS crizotinib 5.0 months (95% CI: 2.9–7.2) versus 14.0 months (95% CI: 8.0–20.1), P < 0.001; OS 17.0 months (95% CI: 6.7–27.3) versus not reached, P = 0.049] and crizotinib followed by next-generation ALK-inhibitor [PFS next-generation inhibitor 5.4 months (95% CI: 0.1–10.7) versus 9.9 months (95% CI: 6.4–13.5), P = 0.039; OS 7.0 months versus 50.0 months (95% CI: not reached), P = 0.001). Conclusions In ALK -rearranged NSCLC co-occurring TP53 mutations predict an unfavorable outcome of systemic therapy. Our observations encourage future research to understand the underlying molecular mechanisms and to improve treatment outcome of the ALK/TP53 co-mutated subgroup. [ABSTRACT FROM AUTHOR]

Objectives The recent success of individualized lung cancer therapy has triggered fundamental changes in clinical research strategies. To date there is a strong focus on early proof of concept trials in genetically preselected small patient subgroups. This analysis focuses on the economic burden caused by such trials for advanced lung cancer patients in a German Comprehensive Cancer Center (CCC). Methods The profit margins between recruiting groups with ≤3 and >3 patients were compared. Clinical and economic data from clinical trials for advanced lung cancer (LC), pharma-sponsored trials (PhST) as well as investigator initiated trials (IIT), conducted between 2011 and 2015 at the Center for Integrated Oncology (CIO) Cologne, were analyzed using a profit-center calculation model. Results 161 patients were enrolled in 27 clinical trials. The key economic parameter determining costs and payments was the ‘trial visits’. In comparison of the two groups (A ≤ 3; B > 3 patients enrolled) we found negative profit margins for the low recruiting group (€ −1444). Concerning the number of visits significant differences were found between PhST and IIT (p = 0.009). Additionally, sub-analysis show structural differences in cost composition by conducting PhST and IIT. Conclusion Trials with low patient numbers and IIT, do not cover the cost. To ensure adequate, cost-covering compensation by pharmaceutical companies CCCs have to thoroughly calculate the cost of early proof of concept trials. The findings of this study also underline the need for novel structures in public funding for investigator-initiated clinical trials in precision medicine. [ABSTRACT FROM AUTHOR]

Synovial sarcoma is a high-grade soft tissue malignancy characterized by a specific reciprocal translocation t(X;18), which leads to the fusion of the SS18 (SYT) gene to one of three SSX genes (SSX1, SSX2 or SSX4). The resulting chimeric SS18-SSX protein is suggested to act as an oncogenic transcriptional regulator. Despite multimodal therapeutic approaches, metastatic disease is often lethal and the development of novel targeted therapeutic strategies is required. Several expression-profiling studies identified distinct gene expression signatures, implying a consistent role of Wnt/β-catenin signaling in synovial sarcoma tumorigenesis. Here we investigate the functional and therapeutic relevance of Wnt/β-catenin pathway activation in vitro and in vivo. Immunohistochemical analyses of nuclear β-catenin and Wnt downstream targets revealed activation of canonical Wnt signaling in a significant subset of 30 primary synovial sarcoma specimens. Functional aspects of Wnt signaling including dependence of Tcf/β-catenin complex activity on the SS18-SSX fusion proteins were analyzed. Efficient SS18-SSX-dependent activation of the Tcf/β-catenin transcriptional complex was confirmed by TOPflash reporter luciferase assays and immunoblotting. In five human synovial sarcoma cell lines, inhibition of the Tcf/β-catenin protein-protein interaction significantly blocked the canonical Wnt/β-catenin signaling cascade, accompanied by the effective downregulation of Wnt targets (AXIN2, CDC25A, c-MYC, DKK1, CyclinD1 and Survivin) and the specific suppression of cell viability associated with the induction of apoptosis. In SYO-1 synovial sarcoma xenografts, administration of small molecule Tcf/β-catenin complex inhibitors significantly reduced tumor growth, associated with diminished AXIN2 protein levels. In summary, SS18-SSX-induced Wnt/β-catenin signaling appears to be of crucial biological importance in synovial sarcoma tumorigenesis and progression, representing a potential molecular target for the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

BackgroundTo evaluate the clinical outcomes of subfoveal haemorrhages secondary to neovascular age-related macular degeneration (AMD), which were treated with intravitreal recombinant tissue plasminogen activator (rTPA)/gas and anti-vascular endothelial growth factor (anti-VEGF) drug or with an intravitreal anti-VEGF monotherapy.MethodsThis is a retrospective pilot study. Patients who received intravitreal rTPA/gas and anti-VEGF injections (n=20, bevacizumab or ranibizumab) were included in group A. Patients who refused prone positioning after rTPA/gas injections and were treated with an anti-VEGF monotherapy (bevacizumab) alone were included into group B (n=10). Changes in baseline visual acuity (VA, Snellen), central retinal thickness (CRT) and haemorrhage size were analysed.ResultsMean baseline VA was 0.15±0.2 and 0.25±0.17 in groups A and B, respectively. At month 4, significant improvement in mean VA was observed in group A (mean difference: +0.1±0.14; P=0.003), and a stabilization in group B (mean difference: +0.008±0.2; P=0.94). CRT decreased significantly by 70 μm in group A (P=0.001) and by 84 μm in group B (P=0.03). The mean size of subfoveal haemorrhage in groups A and B was 20.2 mm2 and 19.1 mm2 at baseline and 0.0 mm2 and 2.0 mm2 at month 4, respectively. The anti-VEGF treatmentrate was 1.6 in group A and 3.0 in group B.ConclusionIn patients with extensive subfoveal haemorrhage secondary to neovascular AMD, the combination therapy of rTPA/pneumatic displacement and anti-VEGF results in mean improvement of VA and stabilization of morphological parameters. If rTPA and pneumatic displacement combination is contraindicated, an anti-VEGF monotherapy may be performed to prevent further visual loss.Eye (2009) 23, 1404–1410; doi:10.1038/eye.2008.267; published online 29 August 2008 [ABSTRACT FROM AUTHOR]