Characterization of Novel Diphenylamine Compounds as Ferroptosis Inhibitors.

Ferroptosis is a form of oxidative cell death that is increasingly recognized as a key mechanism not only in neurodegeneration but also in regulated cell death, causing disease in other tissues. In neurons, major hallmarks of ferroptosis involve the accumulation of lipid reactive oxygen species (ROS) and impairment of mitochondrial morphology and function. Compounds that interfere with ferroptosis could provide novel treatment options for neurodegenerative disorders and other diseases involving ferroptosis. In the present study, we developed new compounds by refining structural elements of the BH3 interacting-domain death agonist inhibitor BI-6c9, which was previously demonstrated to block ferroptosis signaling at the level of mitochondria. Here, we inserted an antioxidative diphenylamine (DPA) structure to the BI-6c9 structure. These DPA compounds were then tested in models of erastin, and Ras-selective lethal small molecule 3 induced ferroptosis in neuronal HT22 cells. The DPA compounds showed an increased protective potency against ferroptotic cell death compared with the scaffold molecule BI-6c9. Moreover, hallmarks of ferroptosis such as lipid, cytosolic, and mitochondrial ROS formation were abrogated in a concentration- and time-dependent manner. Additionally, mitochondrial parameters such as mitochondrial morphology, mitochondrial membrane potential, and mitochondrial respiration were preserved by the DPA compounds, supporting the conclusion that lipid ROS toxicity and mitochondrial impairment are closely related in ferroptosis. Our findings confirm that the DPA compounds are very effective agents in preventing ferroptotic cell death by blocking ROS production and, in particular, via mitochondrial protection. SIGNIFICANCE STATEMENT: Preventing neuronal cells from different forms of oxidative cell death was previously described as a promising strategy for treatment against several neurodegenerative diseases. This study reports novel compounds based on a diphenylamine structure that strongly protects neuronal HT22 cells from ferroptotic cell death upon erastin and Ras-selective lethal small molecule 3 induction by preventing the development of different reactive oxygen species and by protecting mitochondria from ferroptotic impairments.

Impact of TP53 mutation status on systemic treatment outcome in ALK-rearranged non-small-cell lung cancer.

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.

Torpedo Maculopathy Associated with Choroidal Neovascularization.

Background Torpedo maculopathy is a very rare, congenital, usually unilateral hypopigmented lesion in the temporal macula. Material and Methods This retrospective case series describes three patients with torpedo maculopathy. Results The first two cases demonstrate typical clinical and imaging findings of torpedo maculopathy in asymptomatic patients. The third case relates to a symptomatic young patient with a torpedo lesion, a smaller satellite lesion, and evidence of choroidal neovascularization confirmed by fluorescence angiography. In the area of the clinically visible torpedo lesion, spectral domain optical coherence tomography showed atrophy of the outer retina with increased choroidal signalling and a hyperreflective lesion above the retinal pigment epithelium suggestive of choroidal neovascularization. Fundus autofluorescence imaging revealed a hyperautofluorescent rim along the margin of the hypoautofluorescent torpedo lesion. Conclusion In the literature, torpedo lesions are usually regarded as benign lesions with no tendency for progression. The third case demonstrates that torpedo lesions may be associated with choroidal neovascularization, which has been successfully treated with anti-VEGF therapy.

[Switching Therapy from Ranibizumab and/or Bevacizumab to Aflibercept in Neovascular Age-Related Macular Degeneration (AMD): One-Year Results]. / Das klinische Ergebnis eines Therapiewechsels von Ranibizumab und/oder Bevacizumab zu Aflibercept bei neovaskulärer altersabhängiger Makuladegeneration (AMD).

BACKGROUND: The presented study is a retrospective evaluation of switching therapy from ranibizumab and/or bevacizumab to aflibercept in neovascular age-related macular degeneration in patients who had previously given an insufficient response to therapy with ranibizumab and/or bevacizumab. PATIENTS AND METHODS: 96 eyes with neovascular age-related macular degeneration (AMD) were included, which had been pretreated with ranibizumab and/or bevacizumab (T&E), but had responded insufficiently. An injection interval of less than six weeks or permanently persisting intra- and/or subretinal fluid or persistent pigment epithelial detachments (PED) were defined as an insufficient response. The patients were followed for 12 months after switching therapy to aflibercept. The change in central retinal thickness (CRT) was defined as the primary endpoint. Other endpoints were the axial height of PEDs and the injection interval. RESULTS: The primary endpoint, the average CRT, was significantly decreased twelve months after switching therapy to aflibercept (Wilcoxon Nemenyi-McDonald-Thompson post-hoc analysis - 31.36 µm; SD ± 70.64 µm; p < 0.001). Another morphological endpoint, the average axial height of PEDs, also decreased significantly (- 34.10 µm; SD ± 91.90 µm, p < 0.001) from 207.82 µm (SD ± 148.12 µm) at baseline to 173.72 µm (SD ± 132.30 µm) at month 12. Moreover, the average injection interval increased significantly (p < 0.001; Friedman test) from 1.30 months (SD ± 0.19 months) before switching therapy to 1.67 months (SD ± 0.19 months) at month 12 after switching therapy to aflibercept. However, the best corrected visual acuity (BCVA) as a functional endpoint did not significantly improve (+ 0.36 ETDRS letters = 0.0972 p; SD ± 16.94 ETDRS letters). CONCLUSION: In patients with neovascular AMD, who had initially exhibited an inadequate response to ranibizumab and/or bevacizumab, switching therapy to aflibercept improves clinical outcome measures. Besides morphological improvements, such as the decrease of the CRT and the axial height of PEDs, the average injection interval was prolonged. However, visual acuity did not improve.

Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial.

BACKGROUND: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. MATERIALS AND METHODS: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. RESULTS: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. CONCLUSIONS: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.

Intravitreal anti-VEGF therapy for retinal macroaneurysm.

BACKGROUND: We evaluated the effect of intravitreal anti-vascular endothelial growth factor therapy using bevacizumab or ranibizumab for retinal macroaneurysms with macular exudation. METHODS: In a retrospective interventional case series patients with retinal macroaneurysms were treated with either 1.25 mg intravitreal bevacizumab or 0.5 mg ranibizumab as first-line therapy. Patients were imaged by fluorescein angiography and optical coherence tomography. Retreatment was performed in case of persistent intraretinal or subretinal fluid in optical coherence tomography. RESULTS: Ten patients (10 eyes) with macroaneurysm involving the macula were treated with an average of 3.0 intravitreal anti-vascular endothelial growth factor injections. Mean best corrected visual acuity of all patients improved by 17 letters from baseline to the last follow-up visit. In 7 out of 10 patients, the fovea was affected by a secondary edema. In cases with foveal involvement, central retinal thickness decreased from 366 µm at baseline to 266 µm at the last follow-up visit. In the course of treatment 8 out of 10 patients showed evidence of marked regression of macular exsudation. CONCLUSION: Intravitreal anti-vascular endothelial growth factor therapy appears to be a promising treatment alternative to laser treatment in cases of retinal macroaneurysms with macular exudation.

Extra short dental implants supporting an overdenture in the edentulous maxilla: a proof of concept.

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.

Multimodal imaging of autosomal dominant drusen.

BACKGROUND: Malattia Leventinese (ML) is a dominantly inherited macular dystrophy characterized by a radial pattern of drusen in the macular area and on the nasal edge of the optic disc. This case series describes the morphological features of drusen associated with ML using multimodal imaging. HISTORY AND SIGNS: Three patients (two of the same family but only one with the ML phenotype) were analyzed by multimodal imaging including spectral domain optical coherence tomography (SD OCT) and genetic testing. In two patients multiple drusen in the macular region and around the optic nerve head were observed bilaterally. A radial pattern was only seen in one patient. These drusenoid deposits showed early hyperfluorescence in fluorescein angiography (FA) and intense staining in indocyanine green angiography similar to cuticular drusen (basal laminar drusen). The corresponding SD OCT scan revealed two types of deposits. The first, more prominent type, were focal nodular sub-retinal pigment epithelium (RPE) deposits. The second type of deposit appears to be localized on the anterior part of the RPE comparable to subretinal drusenoid deposits (SDD; reticular pseudodrusen). THERAPY AND OUTCOME: A single nucleotide variation c.1033C>T (p.R345 W) in the EFEMP1 gene was found in case 1 (classic ML), but could not be detected in case 2 and 3. So far our patients have not suffered from any visual complaints and have not developed choroidal neovascularization. They will be followed up regularly. DISCUSSION: Multimodal imaging including SD OCT provided new information about the appearance of drusen in eyes with ML/early onset drusen. In addition to the sub-RPE deposits some deposits appear above the RPE, however have different characteristic findings on FA/ICG, autofluorescence, near infrared reflectance and blue light imaging than SDD observed in patients with age-related macular degeneration. SD OCT alone might not be sufficient to characterize these type of drusen in ML.

Response to ranibizumab therapy in neovascular AMD - an evaluation of good and bad responders.

BACKGROUND: Treatment of neovascular age-related macular degeneration (AMD) with Lucentis shows a broad spectrum regarding the course of visual acuity (VA). While some patients show a good response (increase in VA), others disclose much less promising results. PATIENTS AND METHODS: A retrospective data analysis of all eyes treated for neovascular AMD at the University Hospital of Zurich, Switzerland for at least 12 months was carried out. The courses of VA between the 90th (good responders, GR) and the 10th (bad responders, BR) percentiles were compared at 3, 12 and 24 months from baseline. An analysis regarding demographic data, lesion type and size as well as injection frequency and visits was done and predictive factors for GR and BR were evaluated. RESULTS: Marked differences in the course of VA between GR (n = 30) and BR (n = 30) are already observed 3 months from baseline. In GR the gains in VA after 3, 12 and 24 were 15.7 +/- 9 letters ETDRS, 25.3 +/- 7 and 14.0 +/- 14. BR showed a deterioration of 8.3 +/- 11 letters ETDRS after 3, 22.1 +/- 8 after 12 and 23.6 +/- 13 after 24 months. The gender distribution was equal with a higher percentage of female patients (64 % in BR and 66 % in GR). The baseline VA was statistically significantly lower in GR (45.7 +/- 10 vs. 55.4 +/- 11, p < 0.05) than in BR. No other significant differences in baseline data were found, and no predictor for group membership could be identified. CONCLUSIONS: Only the course of VA in the first three months seems to be of value for an estimation of the response to treatment. In the future the response to treatment in the early phase may influence the treatment algorithm and the injection frequency.

[Precision pulse capsulotomy : The new capsulorhexis?] / Präzisionspulskapsulotomie : Die neue Kapsulorhexis?

The manual capsulorhexis created by Neuhann is still the standard procedure for opening the anterior capsule for cataract surgery. A limitation is the inaccuracy in the size and placement of the opening due to manual execution. In addition to the femtosecond laser a possible improvement in the standardization of capsulorhexis is provided by the Zepto procedure (precision pulse capsulotomy, PPC). In this case a 5.25 mm rhexis is created in a standardized fashion with a flexible suction adapter in which a nitinol ring is located. Whether the strength of PPC is comparable or better than that of the manual technique and how it behaves in terms of capsule shrinkage has not yet been finally clarified.

[Intravitreal bevacizumab versus verteporfin and intravitreal triamcinolone acetonide in patients with neovascular age-related macula degeneration]. / Intravitreales Bevacizumab vs. Verteporfin und intravitreales Triamcinolon Acetonid bei Patienten mit neovaskulärer AMD.

AIM: The aim of this study was to compare intravitreal bevacizumab (IVB) and verteporfin therapy in combination with 4 mg intravitreal triamcinolone (PDT-IVTA) in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: A total of 30 eyes of 30 patients with neovascular AMD were included in a prospective, randomized study. Ten eyes received PDT-IVTA with a standard light fluence of 50 J/cm(2) (SPDT-IVTA), ten were treated with PDT-IVTA with a reduced light fluence of 25 J/cm(2) (RPDT-IVTA) and ten received IVB. The main outcome was evaluated using early treatment diabetic retinopathy study (ETDRS) visual acuity, fluorescein angiography and optical coherence tomography (OCT) at baseline as well as at day 1, week 1, 1 month and 3 months after therapy. RESULTS: At the beginning of therapy, the distribution of the groups was balanced. After 3 months, the SPDT-IVTA group showed a non-significant vision loss of seven letters (p<0.3) while a vision loss of 0.5 letters (p<0.9) was found in the RPDT-IVTA group. At the same time, the IVB group had a vision improvement of 11.8 letters (p<0.001). This vision improvement was statistically significant compared to the results of both PDT-IVTA groups (p<0.005). Central retinal thickness (CRT) decreased up to month 3 in the SPDT-IVTA group by 132 microm, in the RPDT-IVTA group by 78 mum and in the IVB group by 138 microm, (p<0.05 in the three groups). No significant difference in the decrease of CRT was found between the treatment groups after 3 months. CONCLUSION: IVB shows significantly better results in vision improvement in the short-term compared to the two PDT-IVTA groups. Within 3 months, all groups showed a comparable decrease in CRT. Long-term follow-up is required to evaluate the safety and treatment efficacy of all treatment modalities.

Economic burden of clinical trials in lung cancer in a German Comprehensive Cancer Center.

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.

Anecortave acetate for the treatment of subfoveal choroidal neovascularization secondary to age-related macular degeneration.

PURPOSE: Anecortave acetate is a novel angiostatic cortisene being evaluated clinically for treatment of exudative age-related macular degeneration (ARMD). A randomized, placebo-controlled, efficacy and safety dose duration study of anecortave acetate for depot suspension (3 mg, 15 mg, 30 mg) in this patient population was completed in June 2003. As part of this trial, 128 patients with subfoveal choroidal neovascularization (CNV) secondary to ARMD were enrolled and treated for up to 2 years by 18 clinical sites in the United States and European Union. METHODS: Study patients were evaluated clinically with detailed ophthalmic examinations, general physical examinations, assessments of best-corrected logMAR visual acuity, and angiographic evaluations. The Digital Angiography Reading Center (New York City, NY) assessed lesion eligibility while the clinical investigators assessed overall patient eligibility prior to treatment. As part of this study, study medication was delivered as a posterior juxtascleral depot using a specially designed curved cannula at 6-month intervals if in the masked investigator's opinion the patient's lesion could benefit from additional treatment. RESULTS: The 2-year efficacy results of this placebo-controlled study demonstrated that RETAANE 15 mg (anecortave acetate for depot suspension) was statistically superior to placebo for stabilization of vision (<3 logMAR line change from baseline) and for inhibition of neovascular lesion growth. There were no serious treatment-related safety issues associated with either the study medication or the procedure for administration. CONCLUSIONS: Anecortave acetate 15 mg for depot suspension is clinically efficacious compared to placebo for treatment of subfoveal exudative ARMD lesions when administered at 6-month intervals as a posterior juxtascleral depot.

Topographic angiography and optical coherence tomography: a correlation of imaging characteristics.

PURPOSE: Topographic angiography (TAG) using confocal scanning laser angiography and optical coherence tomography (OCT) are new imaging modalities that have been introduced during recent years. OCT and TAG imaging were compared to specify the characteristics of each imaging modality. METHODS: TAG using fluorescein angiography (FA) provides a three-dimensional profile of the vascular structures based on the analysis of a set of 32 confocal images over a depth of 4 mm. OCT provides cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex (RPE-CC). The authors compared and evaluated both modalities in 10 patients with predominantly classic choroidal neovascularization (CNV), 10 patients with serous pigment epithelial detachment (PED), and 10 patients with geographic RPE atrophy, all secondary to age-related macular degeneration (ARMD). RESULTS: In patients with classic CNV, TAG detected neovascular structures and delineated their configuration. In PEDs pooling of extravascular fluid is demonstrated, and in geographic RPE atrophy TAG showed reduced choroidal perfusion. Classic CNV was demonstrated by OCT as a hyperreflective band at the level of the RPE-CC, and PED showed a dome-shaped RPE detachment. In geographic RPE atrophy, OCT imaged loss of the RPE band and had an increased depth resolution. CONCLUSIONS: TAG and OCT are useful imaging modalities in the evaluation of ARMD cases. TAG visualizes the vascular configuration and dynamic perfusion and leakage changes. OCT is able to document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. Both modalities may provide further valuable insight into ARMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.

Arguments against a close relationship between non-phosphorylating and phosphorylating glyceraldehyde-3-phosphate dehydrogenases.

Non-phosphorylating NADP-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (EC 1.2.1.9) from spinach leaves was purified to homogeneity using an improved purification procedure. Thus, a major contaminant with molecular mass and ion-exchange properties similar to non-phosphorylating GAPDH was eliminated. Using this pure non-phosphorylating GAPDH, cofactor stereospecificity was determined by 1H NMR. Analysis of the NADPH formed from the hydride transfer from glyceraldehyde-3-phosphate to [4-2H]NADP showed that the enzyme belongs to the A-stereospecific dehydrogenase family. This stereospecificity is the same as that described for the aldehyde dehydrogenase (ALDH) superfamily and opposite to that of the phosphorylating GAPDH. Moreover, results from peptide sequencing analysis suggest a similarity in sequence between the non-phosphorylating GAPDH and ALDHs. Thus, the results taken all together strongly suggest that non-phosphorylating GAPDH belongs to the ALDH family and has no close relationship to the phosphorylating GAPDH class.

Immunostaining for leukocyte common antigen using an amplified avidin-biotin-peroxidase complex method and paraffin sections. A study of 735 hematopoietic and nonhematopoietic human neoplasms.

Antibodies to leukocyte common antigen (LCA) are valuable in surgical pathology in the diagnostic separation of malignant lymphomas from poorly differentiated neoplasms of other types. However, several publications have reported difficulty in obtaining adequate LCA labeling in paraffin-embedded specimens. To assess this problem further, we applied an amplified version of the avidin-biotin-peroxidase complex procedure to 315 formaldehyde-fixed hematopoietic malignancies, and 420 nonhematopoietic tumors that had been similarly processed. All non-Hodgkin's lymphomas were LCA-reactive with this method, whereas none of the nonhematopoietic neoplasms were stained. Twelve of 25 cases of Hodgkin's disease displayed LCA-positivity in Reed-Sternberg cells, but all contained reactive, benign inflammatory cells. Hence, the specificity of the amplified anti-LCA/avidin-biotin-peroxidase technique was 100%, and its sensitivity was 96%. This procedure should allow surgical pathologists to obtain reliable, reproducible staining of hematopoietic neoplasms in paraffin-embedded tissues.

Predictors of alcoholics' acquisition of treatment-related knowledge.

Only modest relationships have been found between cognitive functioning and treatment outcome; there is some indication of better prediction of within-treatment progress. The current study attempted to determine whether either cognitive or sociodemographic/alcohol-related variables were predictive of learning in educational treatment. Eighty-seven male alcoholics were exposed to one hour of instruction on the medical effects of alcohol. Sociodemographic, alcohol-related, and cognitive functioning measures were obtained at the outset of treatment. Knowledge was assessed 24 hours prior to and 24 hours and three weeks after the intervention. Statistically significant increases in knowledge were found both 24 hours and three weeks following the educational intervention; retention of information declined significantly from 24 hours to three weeks post-intervention. Discriminant function analyses using either seven cognitive variables or six alcohol-related/sociodemographic variables significantly discriminated between learners and nonlearners 24 hours after the intervention. The weighted composite of measures in each of the analyses was able to successfully differentiate learners from nonlearners in over 70% of the cases. The findings suggest that the clinician may be able to employ a limited number of variables to differentiate between patients who will and will not be able to acquire knowledge from educational interventions.

Photodynamic therapy with verteporfin: a new treatment in ophthalmology.

Photodynamic therapy (PDT) with verteporfin is a new treatment modality in ophthalmology that has previously shown its effectiveness in treatment of a variety of neoplastic pathologies. In this therapeutic approach, the photosensitizer verteporfin is activated by non-thermal laser light to obtain closure of neovascular structures. Preclinical and clinical studies have indicated that PDT is a safe, selective, and effective treatment for choroidal neovascularization in age-related macular degeneration. No significant damage to the neurosensory retina was found, which explains why PDT does not cause loss of visual acuity and may be used in a larger population than laser photocoagulation. This review summarizes the mechanisms of action of PDT, and the results of preclinical and clinical studies in ophthalmology.

[Chorioretinal anastomosis as unfavourable prognostic factor during photodynamic therapy]. / Chorioretinale Anastomosen als ungünstiger Prognosefaktor bei photodynamischer Therapie.

BACKGROUND: The aim of this study was the documentation of chorioretinal anastomosis in neovascular age-related macular degeneration (AMD) and correlation with functional and angiographic results following photodynamic therapy (PDT). METHOD: A total of 100 patients presenting with neovascular AMD and indication for PDT based on the presence of predominantly classic choroidal neovascularization (CNV), underwent ophthalmoscopic and angiographic screening for chorioretinal anastomosis. Conventional PDT using verteporfin was performed according to the recommended standard procedure. The pre- and post-treatment status at 3 and 6 months post-PDT in all patients and at 1 week in selected patients was documented with respect to the central visual acuity test (ETDRS), ophthalmoscopy as well as fluorescein (FA) and indocyanine green angiography (ICGA). RESULTS: A primary chorioretinal anastomosis was found in 6% ( n=12) of all eyes with CNV and classic PDT indication. Mean visual loss within the first 6 months after therapy was 3 lines indicating lack of visual stabilization according to the PDT study criteria.Furthermore, an increase in visual acuity could not be documented in any case. Angiography demonstrated continuous progression of CNV size although PDT had been uneventful. The characteristic initial occlusion of the CNV with homogeneous hypofluorescence was absent angiographically at 1 week post-PDT. The anastomosis was detected by ICGA in all eyes and by ophthalmoscopy or optical coherence tomography (OCT) in most eyes. DISCUSSION: Chorioretinal anastomosis is not a rare finding associated with predominantly classic CNV. The presence of anastomosis appears to be an unfavourable prognostic factor during PDT. If a chorioretinal shunt is suspected evaluation by ICGA and/or OCT should be performed and the indication for PDT should be rediscussed.