Functional and morphological changes in diabetic macular edema over the course of anti‐vascular endothelial growth factor treatment

Purpose:  To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti‐vascular endothelial growth factor (VEGF) treatment with Ranibizumab. Methods:  A consecutive series of 39 study eyes with centre‐involving DME were included in this study. In all subjects, best‐corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD‐OCT) cross‐sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross‐sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. Results:  Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 μm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = ?1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = ?3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = ?4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = ?1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = ?0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = ?2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. Conclusions:  ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti‐VEGF therapy with Ranibizumab in patients with DME.     

Design and evaluation of a chitosan–aprotinin conjugate for the peroral delivery of therapeutic peptides and proteins susceptible to enzymatic degradation

One main barrier for the peroral administration of therapeutic peptides and proteins is the enzymatic barrier, that is mediated by luminally secreted and membrane bound proteolytic enzymes. It was the aim of the study to synthesise, characterise and evaluate a novel polymer–inhibitor conjugate in order to improve the bioavailability of orally-administered peptides and proteins. The trypsin/chymotrypsin inhibitor aprotinin was covalently bound to chitosan. The percentage of the inhibitor in the polymer–inhibitor conjugate (m/m) was determined to be between 1.11 ± 0.36 and 1.92 ± 0.05%. In vitro enzyme assays clearly demonstrated the potential of the novel conjugate to inhibit trypsin and chymotrypsin. Moreover, studies in rats were performed to evaluate the efficacy of the conjugate in vivo. Eight hours after oral administration of tablets containing insulin and the novel chitosan–aprotinin conjugate, the mean blood glucose level decreased to 84 ± 6%. In contrast, the mean blood glucose level in the control group increased to 121 ± 8% of the initial measured blood glucose level. In conclusion it was demonstrated that chitosan–aprotinin conjugate represents a novel and promising tool for the oral administration of therapeutic peptides and proteins susceptible to enzymatic degradation caused by trypsin and chymotrypsin.     

Update Breast Cancer 2022 Part 5 – Early Stage Breast Cancer

The treatment of patients with early stage breast cancer has changed in recent years due to the introduction of pembrolizumab, olaparib, and abemaciclib. These and other drugs with the same class of active ingredient are currently in trial for various indications. This review article summarizes the latest results that have either been presented at major conferences such as the ESMO 2022 or published recently in international journals. This includes reports on newly discovered breast cancer genes, atezolizumab in neoadjuvant therapy in HER2-positive patients, long-term data from the APHINITY study, and on how preoperative peritumoral application of local anesthetics can influence the prognosis. We also present solid data on dynamic Ki-67 from the ADAPT studies.Key words: breast cancer, surgery, chemotherapy, therapy standard     

Synthesis of Zeolites from Fine-Grained Perlite and Their Application as Sorbents

The hydrothermal alteration of perlite into zeolites was studied using a two-step approach. Firstly, perlite powder was transformed into Na-P1 (GIS) or hydro(xy)sodalite (SOD) zeolites at 100 °C and 24 h using 2 or 5 M NaOH solutions. Secondly, the Si:Al molar ratio of the reacted Si-rich solution was adjusted to 1 by Na-aluminate addition to produce zeolite A (LTA) at 65 or 95 °C and 6 or 24 h at an efficiency of 90 ± 9% for Al and 93 ± 6% for Si conversion. The performance of these zeolites for metal ion removal and water softening applications was assessed by sorption experiments using an artificial waste solution containing 4 mmol/L of metal ions (Me²⁺: Ca²⁺, Mg²⁺, Ba²⁺ and Zn²⁺) and local tap water (2.1 mmol/L Ca²⁺ and 0.6 mmol/L Mg²⁺) at 25 °C. The removal capacity of the LTA-zeolite ranged from 2.69 to 2.86 mmol/g for Me²⁺ (=240–275 mg/g), which is similar to commercial zeolite A (2.73 mmol/g) and GIS-zeolite (2.69 mmol/g), and significantly higher compared to the perlite powder (0.56 mmol/g) and SOD-zeolite (0.88 mmol/g). The best-performing LTA-zeolite removed 99.8% Ca²⁺ and 93.4% Mg²⁺ from tap water. Our results demonstrate the applicability of the LTA-zeolites from perlite for water treatment and softening applications.     

Influence of fluoride concentration and ethanol pre-treatment on the reduction of the acid susceptibility of enamel

Objective

To determine the association between KOH-soluble and structurally bound fluoride uptake and the erosion resistance of enamel, respectively. Additionally, the effect of enamel pre-treatment with ethanol before fluoridation was assessed.

Methods

Sixty bovine incisors (4 specimens/tooth) were randomly allocated to six groups (A-F). Samples 1 and 2 remained untreated, serving as control at baseline. Pre-treatment of the samples was performed for 5 min with 99% ethanol (groups A, B and C) or physiologic saline (groups D, E and F). Samples 3 and 4 were treated either with 0.5% (groups A and D), 1.0% (groups B and E) or 1.5% (groups C and F) fluoride solution. In samples 1 and 3, uptake of KOH-soluble and structurally bound fluoride was determined. Samples 2 and 4 were used for the determination of acid susceptibility by immersion in 1 ml HCl for 30 s. Calcium release into HCl was assessed by atomic absorption spectroscopy. Differences between the groups were calculated by unpaired t-tests (p < 0.05).

Results

Mode of pre-treatment showed no influence on fluoride acquisition. KOH-soluble and structurally fluoride uptake increased with increasing fluoride concentrations. Highest acid resistance was observed after treatment with 1% fluoride solution for both kinds of pre-treatment followed by 1.5% and 0.5% fluoride solution.

Conclusion

Dose-dependency was observed for enamel fluoride acquisition but not for acid resistance.     

Cortical parameters predict bone strength at the tibial diaphysis,but are underestimated by HR-pQCT and μCT compared to histomorphometry

Cortical bone and its microstructure are crucial for bone strength, especially at the long bone diaphysis. However, it is still not well-defined how imaging procedures can be used as predictive tools for mechanical bone properties. This study evaluated the capability of several high-resolution imaging techniques to capture cortical bone morphology and assessed the correlation with the bone's mechanical properties. The microstructural properties (cortical thickness [Ct.Th], porosity [Ct.Po], area [Ct.Ar]) of 11 female tibial diaphysis (40–90 years) were evaluated by dual-energy X-ray absorptiometry (DXA), high-resolution peripheral-quantitative-computed-tomography (HR-pQCT), micro-CT (μCT) and histomorphometry. Stiffness and maximal torque to failure were determined by mechanical testing. T-Scores determined by DXA ranged from 0.6 to −5.6 and a lower T-Score was associated with a decrease in Ct.Th (p ≤ 0.001) while the Ct.Po (p ≤ 0.007) increased, and this relationship was independent of the imaging method. With decreasing T-Score, histology showed an increase in Ct.Po from the endosteal to the periosteal side (p = 0.001) and an exponential increase in the ratio of osteons at rest to those after remodelling. However, compared to histomorphometry, HR-pQCT and μCT underestimated Ct.Po and Ct.Th. A lower T-Score was also associated with significantly reduced stiffness (p = 0.031) and maximal torque (p = 0.006). Improving the accuracy of Ct.Po and Ct.Th did not improve prediction of the mechanical properties, which was most closely related to geometry (Ct.Ar). The ex-vivo evaluation of mechanical properties correlated with all imaging modalities, with Ct.Th and Ct.Po highly correlated with the T-Score of the tibial diaphysis. Cortical microstructural changes were underestimated with the lower resolution of HR-pQCT and μCT compared to the histological ‘gold standard’. The increased accuracy did not result in an improved prediction for local bone strength in this study, which however might be related to the limited number of specimens and thus needs to be evaluated in a larger collective.     

Zur Behandlung des veralteten Kahnbeinbruches und der Kahnbeinpseudarthrose der Hand

Ohne ZusammenfassungMit 12 Textabbildungen