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Non-small cell lung cancer (NSCLC) has made a remarkable development in recent decades with respect to its perception. In the late 1990s it was the "problem child" as the main cause of cancer with increasing tendencies, especially in women and with a pronounced stigmatization. It is now the role model as a biologically rational targeted treatment based on molecular dependencies of the tumor with a vast improvement of the traditionally poor survival times. Molecular tumor boards have long followed the NSCLC example in the assessment of targeted treatment approaches for other tumor entities. This review article gives an overview of the current possibilities for targeted treatment of NSCLC, which nowadays are applicable for nearly one third of all patients with NSCLC., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: The gold standard therapy for full-thickness macular holes (FTMH) is vitrectomy (PPV) with peeling of the internal limiting membrane (ILM), gas tamponade of the vitreous cavity and postoperative face-down positioning. Nevertheless, eyes with large macular holes (> 400 µm) and surgical failures remain difficult to manage. Recently, ILM transplantation (ILM-TX) techniques were developed with acceptable results, advocating different mechanisms of hole closure: in such a setting, the ILM could serve as a scaffold for neuronal tissue in the pedicle ILM flap technique or the ILM could induce a contraction of the FTMH rims through shrinking of a folded ILM plug., Patients/material and Methods: This retrospective study evaluates the functional and anatomic outcomes following ILM-TX for large FTMH and failed FMTH surgery. Large holes (group 1) were treated by the pedicle flap and the plug technique. Persistent holes following vitrectomy and ILM peeling (group 2) were treated with the plug technique. All ILM-TX were performed under perfluorocarbon liquid (PFCL) with a subsequent silicone oil tamponade., Results: In group 1 (6 eyes), three eyes had a free ILM graft and three eyes underwent a pedunculated ILM-TX. The mean best corrected visual acuity (BCVA, LogMar) before primary ILM-TX was 1.18 ± 0.54 with a mean initial hole size of 681 ± 106 µm and a photoreceptor defect (PRD) of 1829 ± 474 µm. Five of six eyes showed a postoperative anatomical macular hole closure (83%). The mean BCVA after a mean follow-up of 9.3 ± 5.1 months was 0.83 ± 0.31 after a free ILM graft and 0.95 ± 0.79 after a pedunculated ILM flap. The PRD reduced to 1781 ± 713 µm after a free ILM graft and 1148 ± 378 µm after a pedunculated ILM flap. In group 2 (7 eyes), all patients had failed initial macular hole surgery closure. Prior to free ILM-TX BCVA was 1.05 ± 0.41, the hole size was 433 ± 183 µm and PRD was 2012 ± 718 µm. After a mean of 9.6 ± 4.1 months following ILM-TX, in six of seven eyes the FTMH hole was closed (86%), BCVA improved to 0.53 ± 0.34 and the PRD shortened to 843 ± 291 µm., Conclusion: In most cases, with large FTMH or holes after failed vitrectomy plus ILM peeling, ILM-TX allows a hole closure. Functional outcomes show stabilization and sometimes even a slight improvement., Competing Interests: Die Autoren geben an, dass kein Interessenkonflikt besteht., (Georg Thieme Verlag KG Stuttgart · New York.)

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., (Georg Thieme Verlag KG Stuttgart · New York.)

Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

Background: Up-regulated expression of the vascular endothelial growth factor (VEGF) in von Hippel-Lindau (VHL) disease has been postulated to induce retinal hemangioblastoma. Intravitreal injections of anti-VEGF drugs might provide a new therapeutic option in this condition., Methods: In a single case decision a patient with active retinal hemangioblastomas due to VHL disease received repeated intravitreal injections of 0.5 mg ranibizumab., Results: Subsequent to intravitreal anti-VEGF therapy, the signs of activity of the retinal hemangioblastomas slowly regressed., Conclusions: Intravitreal anti-VEGF therapy might, as monotherapy or as combination therapy, offer a new treatment option for retinal hemangioblastoma.

Purpose: The purpose of this study was to evaluate the early treatment response following systemic and intravitreal bevacizumab therapy in patients with neovascular age-related macular degeneration (AMD)., Patients and Methods: In a prospective cohort study 12 eyes with neovascular AMD were treated with 5 mg/kg systemic bevacizumab, and 13 eyes with 1 mg intravitreal bevacizumab. Systemic therapy was given three times at 2-week intervals, intravitreal therapy up to three times at 4-week intervals. Patients were evaluated according to best corrected visual acuity (VA) and optical coherence tomography (OCT) at baseline as well as at week 1, week 4 and week 12 after therapy. Fluorescein angiography (FA) was performed at baseline and week 12., Results: Systemic and intravitreal bevacizumab therapy showed a treatment response within one week. Visual acuity improved at week 1 by 4.9 letters from baseline in the systemic and by 6.9 letters in the intravitreal treatment group. Central retinal thickness (CRT), as measured by OCT decreased by 51.9 microm and 176.4 microm, respectively. At month 3 a persistent treatment effect was detectable. Mean gain in visual acuity was 11 letters in the systemic and 8.3 letters in the intravitreal group, CRT had decreased by 100 microm and 153.8 microm, respectively. Leakage as evaluated by FA was significantly reduced or absent in all patients., Conclusion: The early treatment responses following systemic and intravitreal bevacizumab appear to be similar. Both groups show improvement in VA and decrease in CRT within 1 week and up to 3 months. Long-term follow-up is required to evaluate the safety and treatment durability of both treatment modalities using bevacizumab.

Vascular endothelial growth factor (VEGF) is considered to play an essential role in the pathogenesis of age-related macular degeneration due to its vascular permeability-inducing and angiogenic properties. Ranibizumab, a small antibody fragment designed to competitively bind all VEGF isoforms, passes after intravitreal injection all retinal layers reaching the retinal pigment epithelium-choroid complex. Experimental animal models showed the drug to be safe and effective. Subsequently, Phase I/II clinical trials conducted in patients with neovascular AMD demonstrated a good safety profile, and a significant functional benefit. Ranibizumab therapy repeated every four weeks for the treatment of neovascular AMD is currently in Phase III clinical trials. Combination therapy trials aiming for improved treatment durability and effectiveness are currently ongoing as well as new treatment strategies using intermittent, optical coherence tomography (OCT) guided therapy. Anti-VEGF therapy using Ranibizumab is a promising new treatment option for neovascular AMD.

Purpose: The purpose of this study was to evaluate the impact of photodynamic therapy (PDT) on the regulation of angiogenic factors such as vascular endothelial growth factor (VEGF) and pigment epithelium derived factor (PEDF) in human eyes., Methods: Eyes of patients with untreatable malignancy served as the study eyes (n = 2), age-matched donor eyes were used as controls (n = 2). Standard Verteporfin-PDT was applied to intact areas of the posterior pole. One week after PDT the eyes were examined by ophthalmoscopy as well as fluorescein (FA) and indocyanine green angiography (ICGA). After enucleation the eyes were processed for LM/EM histology. Immunolabeling using specific antibodies against VEGF and PEDF was performed in PDT-treated areas, untreated collateral areas of study eyes and untreated areas of control eyes., Results: All PDT-treated areas demonstrated a typical choroidal hypofluorescence on FA/ICGA. In LM/EM histology a selective damage of choriocapillary endothelial cells was found. VEGF expression was localized only to choriocapillary endothelial cells and focally in larger choroidal vessels of PDT-treated areas. Untreated areas of study eyes and controls were VEGF-negative. PEDF staining was observed in retinas and RPE of all eyes, but only choroidal endothelial cells of PDT-treated areas showed a PEDF-positive reactivity., Conclusion: PDT not only induces structural and angiographic, but also biological effects in human eyes. VEGF and PEDF expression can be documented in choroidal endothelial cells following PDT and could have an impact on the recovery process after treatment.

Purpose: Photodynamic therapy (PDT) induces occlusive and regenerative effects in choroidal neovascularization (CNV) and physiological choroid. The process of vascular alteration is documented quantitatively and qualitatively by three-dimensional angiography., Method: In a prospective, randomized trial 30 patients with subfoveal CNV due to age-related macular degeneration (AMD) were treated with PDT or placebo. Fluorescence series with 32 tomographic images over a 4-mm depth were analyzed topographically and reproduced in a three-dimensional display., Results: At initial presentation CNV lesions were documented as a well-defined prominence in all patients. In the verteporfin group CNV height continuously decreased with each interval. In the placebo group CNV slightly increased in height during the first 6 months and remained stable at about 90% of the initial prominence at long-term follow-up. After 12 months 44% of the patients in the verteporfin group developed an additional choroidal defect., Conclusion: Three-dimensional angiography offers a reliable documentation of CNV progression and regression during PDT. A decrease in CNV size is associated with an increase in choroidal perfusion defects.

Objective: Evaluation of efficacy of photodynamic therapy (PDT) for classic choroidal neovascularization (CNV) beyond the common indication., Methods: A group of 256 patients was treated with photodynamic therapy from January to December 2000. Ten of these patients had a predominantly classic CNV due to angioid streaks (5), parafoveal telangiectasia (2), or chorioretinitis (3). In two patients an idiopathic origin of the CNV was presumed. Another 21 patients showed a juxtafoveal classic membrane (12) or a recurrence after laser photocoagulation (9). Visual acuity was evaluated, also in correlation to age and CNV size. Continuous follow-up of CNV and leakage size was performed with fluorescein angiography., Results: Overall 85% of the patients showed visual stabilization or improvement during an average observation period of 10.5 months. A correlation was found between age and visual improvement favoring younger patients; however, no correlation was found between visual improvement and CNV size. CNV and leakage size decreased moderately over the 9-month follow-up from 1.81/3.45 mm(2) to 1.61/2.60 mm(2)., Conclusion: PDT shows efficacy for classic choroidal neovascularization beyond the common indication.

Purpose: ICG angiography (ICGA) was used to document the effect of repeated PDT (verteporfin) on size and leakage of choroidal neovascularisation in age-related macular degeneration (AMD) and treatment-related side effects on the choroid., Methods: Forty-two patients were followed over 24 months in a clinical trial for PDT in AMD. The ICGAs were performed every 3 months with a confocal laser scanning system. Patients received repeated verteporfin treatment. At each control visit, the patients were retreated if leakage was present in fluorescein angiography (FA)., Results: A continuous, highly significant reduction in CNV size and leakage area was found over 24 months. The initial CNV size dropped by 23% from 3.86 mm2 to 2.98 mm2. The leakage area in the late phase of the angiogram decreased by 30.3% from 5.0 mm2 to 3.5 mm2. A significant side effect of PDT on the choroid was documented by an increased hypofluorescent area in ICGA. The maximum size of the hypofluorescent area was reached after 12 months. At month 24, the choroidal fluorescence showed recovery in respect to area and intensity of fluorescence. But hypofluorescence surrounding the CNV lesion was already present in 40 out of 42 eyes before treatment., Conclusion: The ICGA confirms that repeated PDT treatments lead to a significant reduction in CNV size and leakage area over as long as 2 years. CNV lesions are surrounded by choriocapillary hypofluorescence in ICGA. PDT causes further hypoperfusion of the choroid but in the long-term significant recovery of choroidal perfusion was shown.

Background: Photodynamic therapy is a new option for treatment of choroidal neovascularisation in patients with age-related macular degeneration. But choroidal changes and associated angiographic characteristics have not been further evaluated., Patients: Indocyanine green angiography was used to follow 38 patients with subfoveal choroidal neovascularisation in age-related macular degeneration over up to two years. All patients were treated with the photosensitizer Benzoporphyrin Derivative-MA receiving either a single or triple treatment., Results: Indocyanine green angiography shows two effects of photodynamic therapy. On the one hand a selective and lasting closure of choroidal neovascularisation was documented. Choroidal neovascularisation-size and leakage was significantly reduced in the entire treatment group to 20.7% and 28.3% one week after treatment, followed by a slow increase to 33.3% and 41.2% at up to two years longterm follow up. On the other hand photodynamic therapy causes typically a peri-lesional hypofluorescence in Indocyanine green angiography. This hypofluorescence is most likely due to choroidal hypoperfusion and vascular endothelial changes. A continuous increase in fluorescence was shown, reaching again 90% of the pretreatment intensity at 3 months, documenting a good recovery of the choroidal network., Conclusion: The results show that photodynamic therapy is an alternative treatment in age-related macular degeneration with choroidal, subfoveal neovascularisation. Indocyaningreen angiography reflects well choroidal changes associated with this therapy and may be helpful to choose treatment intervals.

Purpose: Photodynamic therapy (PDT) has been shown to provide immediate occlusion of choroidal neovascularization (CNV), followed by recurrent leakage after single PDT in the majority of the cases after 3 months. Indocyanine green angiography (ICG-A) was used to evaluate completeness of CNV occlusion, effects on physiological choroid and patterns of CNV recurrence., Methods: ICG-A was performed using a confocal laser scanning ophthalmoscope (HRA) before PDT at 1 week, 4 and 12 weeks following PDT. Twenty patients with single and 10 patients with repeated PDT treatments with administration of benzoporphyrin derivative and radiant exposures between 50 and 150 J/cm2 were evaluated., Results: Before PDT well-defined CNV was detectable during early ICG-A in all lesions. Depending on the number of treatments, CNV was absent in early phase ICG-A in 46-83%. CNV reappeared at week 4 in many and at 12 weeks in 77 (66%) of the cases. The treated area regularly showed hypofluorescence, which persisted until week 12. The intensity of choroidal hypofluorescence showed wide interindividual variability. Recurrence may originate from persistent feeder vessels., Conclusion: With ICG-A we demonstrated that PDT induces hypofluorescence of CNV and choroid possibly due to perfusion changes or blockade phenomena. Recurrence may be due to reperfusion of the preexisting CNV or regrowth from feeder vessels.

This investigation in several hospitals of the Federal Republic of Germany attempts for the first time to demonstrate the effects of soft bedding on the patients' condition on hand of well known and in other disciplines well established criteria. It could be shown that the softness of the mattress causes considerable problems for the patient. Furthermore, it becomes clear that the extent of nursing increases markedly with a very soft bedding of the patient in order to compensate for the disadvantages arising from it. Materials used in the prevention of bed sores (so called antidecubitus mattresses) have to be evaluated critically. Nurses must attempt to determine which kind of mattress ought to be used. If the mobility of the patient is not to be restricted even more, the use of a harder mattress may have to be considered.

Contamination of soil by toxic substances, in particular from hazardous waste and air pollution, is not only an important environmental medical problem but also has far-reaching effects on the community. Environmental toxicological assessment is based on the different types of use taking the paths of ingestion into consideration. In the following article the scheme by Eikmann and Kloke systematizes this approach. Orientation values (soil values) for metals and several harmful organic substances for different types of use are presented.

In 1990, the State of North-Rhine-Westphalia established an ordinance on the quality of playground soil and sand. This ordinance includes guideline values for toxic metals (arsenic, lead, cadmium, chromium) in playground soil not covered by vegetation and quality standards for sand to be applied on playgrounds. Additionally guideline values were set for mercury, nickel and thallium. The guideline values include two categories: guideline value I represents the upper limits (95-percentiles) of the background levels of toxic metals generally found in upper soil layers in the State of North-Rhine-Westphalia. Guideline values II ("action levels") were selected on the basis of toxicological considerations. In cases where concentrations of metals above these guideline values are detected, immediate actions (urgent redevelopment measures) are required. Quality standards for playground sand were established to ensure that only noncontaminated sand is applied for playgrounds.

The increasing number of discussions on the influence of toxic environmental factors, including SIDS, prompted systematic postmortem chemical-toxicological investigations to be carried out on 54 SIDS cases and 2 control cases of the same age group. Tissue levels of arsenic, lead, cadmium, mercury, and pentachlorphenol, as well as other organic noxious agents, were measured in several organs. In addition, the COHb concentrations were determined. In spite of the widely scattered values, the extreme levels measured and the arithmetic means and median averages of As, Pb, Cd, Hg, PCP, and COHb had no more range in concentrations than can be expected for toxic effects - according to present knowledge anyway. It was observed that infants from an urban environment showed no greater concentration of noxious agents than did infants from rural regions. There were also no differences between SIDS cases and the controls, nor was there a correlation between infections of the respiratory system that are often morphologically detected - including laryngitis - and higher concentrations of these agents in the organs of SIDS cases.