c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI) model of Alzheimer's disease.

Treatments for Alzheimer's disease have primarily focused on removing brain amyloid plaques to improve cognitive outcomes in patients. We developed small compounds, known as BK40143 and BK40197, and we hypothesize that these drugs alleviate microglial-mediated neuroinflammation and induce autophagic clearance of neurotoxic proteins to improve behavior in models of neurodegeneration. Specificity binding assays of BK40143 and BK40197 showed primary binding to c-KIT/Platelet Derived Growth Factor Receptors (PDGFR)α/ß, whereas BK40197 also differentially binds to FYVE finger-containing phosphoinositide kinase (PIKFYVE). Both compounds penetrate the CNS, and treatment with these drugs inhibited the maturation of peripheral mast cells in transgenic mice, correlating with cognitive improvements on measures of memory and anxiety. In the brain, microglial activation was profoundly attenuated and amyloid-beta and tau were reduced via autophagy. Multi-kinase inhibition, including c-KIT, exerts multifunctional effects to reduce neurodegenerative pathology via autophagy and microglial activity and may represent a potential therapeutic option for neurodegeneration.

ß-amyloid monomer scavenging by an anticalin protein prevents neuronal hyperactivity in mouse models of Alzheimer's Disease.

Hyperactivity mediated by synaptotoxic ß-amyloid (Aß) oligomers is one of the earliest forms of neuronal dysfunction in Alzheimer's disease. In the search for a preventive treatment strategy, we tested the effect of scavenging Aß peptides before Aß plaque formation. Using in vivo two-photon calcium imaging and SF-iGluSnFR-based glutamate imaging in hippocampal slices, we demonstrate that an Aß binding anticalin protein (Aß-anticalin) can suppress early neuronal hyperactivity and synaptic glutamate accumulation in the APP23xPS45 mouse model of ß-amyloidosis. Our results suggest that the sole targeting of Aß monomers is sufficient for the hyperactivity-suppressing effect of the Aß-anticalin at early disease stages. Biochemical and neurophysiological analyses indicate that the Aß-anticalin-dependent depletion of naturally secreted Aß monomers interrupts their aggregation to neurotoxic oligomers and, thereby, reverses early neuronal and synaptic dysfunctions. Thus, our results suggest that Aß monomer scavenging plays a key role in the repair of neuronal function at early stages of AD.

Patient-Reported Outcomes following Tibial Plateau Fractures: Mid- to Short-Term Implications for Knee Function and Activity Level.

Background: Patients with complex proximal tibial plateau fractures (TPFs) tend to overestimate the prognosis of their injury, potentially due to factors such as a limited understanding, optimism, and the influence of the pain intensity. Understanding the reasons behind this misperception is crucial for healthcare providers to effectively communicate with patients and establish realistic expectations for treatment outcomes. The purpose of this study was to analyze the outcomes of TPFs, with a particular focus on patient-reported outcome measures concerning functional recovery, pain levels, and overall satisfaction with treatment. The authors aim to provide valuable insights into the realistic expectations and potential limitations that patients may encounter during their recovery journey. Methods: In this retrospective single-center study, all surgically treated TPFs between January 2014 and December 2019 with a minimum follow-up of 12 months were included. Several patient-reported outcome measures were obtained, including the International Knee documentation Committee Score (IKDC), Lyholm score, Tegner score, and visual analog scale (VAS) for pain. Fractures were classified according to Schatzker, and then subgrouped into simple (Schatzker I-III) and complex (Schatzker IV-VI) fractures. Results: A total of 54 patients (mean age 51.1 ± 11.9 years, 59.3% female) with a mean follow-up time of 3.9 years were included. Schatzker II fractures were present in 48% (n = 26) of the cases, with Schatzker III in 6% (n = 3), Schatzker IV fractures in 6% (n = 3), and Schatker VI fractures in 41% (n = 22) of the cases. All outcome scores showed a significant improvement between the first year after surgery and the last follow-up (mean: 3.9 years). Simple fractures showed significantly lower patient-reported outcomes when compared to the preinjury state; however, good to excellent results were observed. Patient-reported outcomes of complex fractures showed no significant changes in the study period with good to excellent results. When it comes to the Lysholm score, there were no significant differences in the outcome between simple and complex fractures. Furthermore, there was a return-to-sports rate of 100%, with high rates of changing sporting activity in 25% (simple fractures) and 45% in complex fractures. Conclusions: The data from this study showed that both simple and complex tibial plateau fractures show favorable outcomes at the midterm follow-up, and that injury severity does not correlate with worse results. While patients may tend to overestimate the recovery speed, this research highlights the importance of long-term follow-up, demonstrating a substantial improvement between one year post-surgery and the final evaluation. Return-to-sports rates were high, with adjustments needed for certain activities. However, patients should recognize the need to shift to lower-impact sports and the lengthy recovery process.

Design, synthesis and biological evaluation of Nucleosidic CD99 inhibitors that selectively reduce Ewing sarcoma viability.

Ewing Sarcoma (ES) is a cancer of bone and soft tissues affecting mostly children and young adults. Aggressive progression and poor prognosis of this malignancy call for novel and targeted treatments. CD99 is a transmembrane protein that is abundantly expressed on ES cells and is a diagnostic marker for the disease. ES cells are selectively sensitive to CD99 inhibition compared to most normal cells and other tumors. Therefore, CD99 is a good molecular target for ES treatment. Clofarabine and cladribine are two FDA approved drugs that are administered for their inhibitory acts on DNA synthesis to treat relapsed or refractory acute lymphoblastic and myeloid leukemia. They have also been shown to directly bind to CD99 and inhibit ES growth through a distinct mechanism. In the current study, we designed, synthesized and tested new ES specific derivatives of both drugs that would continue to target CD99 but with expected reduction in cellular membrane permeability and rendered unsuitable for inhibiting DNA synthesis. By using commercially available clofarabine and cladribine purine nucleoside analogs, we modified the primary alcohol moiety at the deoxyribose C-5' terminal site to suppress phosphorylation and thus inhibition of subsequent DNA synthesis pathways. In addition, we incorporated a variety of polar groups in the ribose and purine rings to reduce membrane permeability and investigated the effects of configurational changes in the sugar moiety. Among 26 new derivatives, we identified two compounds, BK50164 and BK60106, that cause cell death specifically in ES primarily due to inhibition of CD99 but not via inhibition of DNA synthesis. These findings provide a road map for the future development selective CD99 inhibitors for targeted treatment of ES.

Changing patterns in the epidemiology of tibial plateau fractures: a 10-year review at a level-I trauma center.

PURPOSE: Mobility patterns of western societies have been changing due to ongoing demographic change. Therefore, continuously updated epidemiological data on fracture morphology and treatment strategies are needed. METHODS: This retrospective single-center study included all tibial plateau fractures (TPF) between January 2011 and December 2020 in a level-I trauma center in Central Europe. Epidemiology, trauma mechanism and fracture morphology were analyzed. Age- and sex-specific differences regarding fracture classification (Schatzker, AO/OTA, Moore) and changes during the study period are highlighted. RESULTS: A total of 607 patients (55.2% women, 44.8% men, mean age 52.9 years (± 17.9)) were included in the study, 462 (76.1%) thereof having undergone surgical treatment. Over the decade, an increase in mean age (+ 7.4 years; p = 0.10), incidence (+ 68%; p < 0.05) and low-energy trauma was observed, with the highest peak in elderly women. Within classifications, AO/OTA 41-B3 (24.9%), Schatzker II (26.8%) and Moore V (46.6%) fractures were the most common. CONCLUSION: Incidence (+ 68%), mean age and fractures with signs of knee dislocation of tibial plateau fracture increased over the last decade and low-energy trauma mechanism are more frequent. As the increase in incidence is mainly seen in older women, the comorbidities and need for immediate postoperative full weight-bearing have to be considered in treatment strategies.

3D osteotomies-improved accuracy with patient-specific instruments (PSI).

PURPOSE: Three-dimensional (3D) printed patient-specific instruments (PSI) have been introduced to increase precision and simplify surgical procedures. Initial results in femoral and tibial osteotomies are promising, but validation studies on 3D planning, manufacturing of patient-specific cutting blocks and 3D evaluation of the attained results are lacking. METHODS: In this study, patient-specific cutting blocks and spacers were designed, fabricated, and used to perform a high tibial osteotomy (HTO). After segmentation of CT data sets from 13 human tibiae, 3D digital planning of the HTO was performed with a medial opening of 8 mm. These 3D models were used to fabricate patient-specific cutting blocks and spacers. After the surgical procedure, accuracy was evaluated measuring 3D joint angles and surface deviations. RESULTS: The lowest mean deviation was found to be 0.57° (SD ± 0.27) for the MPTA. Medial and lateral tibial slope deviated from the 3D planning by an average of 0.98° (SD ± 0.53) and 1.26° (SD ± 0.79), respectively, while tibial torsion deviated by an average of 5.74° (SD ± 3.24). Color analysis of surface deviations showed excellent and good agreement in 7 tibiae. CONCLUSION: With 3D cutting blocks and spacers, the 3D planning of the HTO can be translated into reality with small deviations of the resulting joint angles. Within this study, the results of the individual steps are examined for errors and thus a critical evaluation of this new and promising method for performing patient-specific HTOs is presented.

Intraoperative alignment correlates well with long standing radiographs - The X-ray grid method in complex knee surgery.

OBJECTIVE: While long standing radiographs (LSR) represent the gold standard for preoperative alignment assessment and planning of lower limb deformity corrections, there is no consensus about the intraoperative alignment assesments (IAC) due to various limitations of the common methods. The present study introduces a radiolucent X-ray grid with integrated radiopaque lines explicitly designed for fluoroscopic IAC and evaluates its reliability in comparsion to the LSR. METHODS: Patients with posttaumatic and congenital lower limb deformity surgery and preoperative LSR as well as fluoroscopic IAC utilizing the X-ray grid were retrospectively included to the study. The mechanical axis deviation (MAD) in percentage of the maximum tibial width from the medial to the lateral in comparison between the image pairs was set as primary outcome parameter. Multiple rater and measurements determined intra- and interobserver reliabilit of both imaging methods. In addition, the effects of age, gender, body mass index (BMI), etiology, joint line convergence angle (JLCA), and extent varus or valgus deformity were analysed. RESULTS: A total of 84 patients were finally included. The mean absolute difference of MAD between the two techniques was 7.2 ± 0.8%. MAD between the LSR and IAC correlated at a high level (R = 0.96, p <0.001). The agreement decreased with increasing extent of deformity (p <0.01) and with higher deviation of JLCA between LSR and IAC (p <0.01). Intra- and interobserver concordance correlation coefficient (CCC) for MAD measurements were 0.99 for both imaging techniques. CONCLUSION: Fluoroscopy combined with the X-ray grid method is a valid tool for intraoperative assessment of lower limb alignment in deformity correction surgery, and the correlation between LSR and IAC is better than in other similar techniques described in the literature. However, in case of severe coronal alignment deformity and highly divergent JLCA, the agreement between both imaging techniques decreases significantly.

Reliability of 3D planning and simulations of medial open wedge high tibial osteotomies.

Purpose: In medial open-wedge high tibial osteotomy (HTO) hinge axis and osteotomy plane influence the resulting anatomy, but accurate angular quantifications using 3D-planning-simulations are lacking. The objectives of this study were developing a standardized and validated 3D-planning method of an HTO and to perform several simulated realignments to explain unintended anatomy changes. Methods: The cutting direction of the main osteotomy was defined parallel to the medial tibial slope and the hinge axis 1.5 cm distal to the lateral plateau. For interobserver testing, this 3D planning was performed on 13 digital models of human tibiae by two observers. In addition, four different hinge axis positions and five differently inclined osteotomy planes each were simulated. The osteotomy direction ranged from medial 0°-30° anteromedial, while the tilt of the osteotomy plane compared to the tibial plateau was -10° to +10°. All anatomic angular changes were calculated using 3D analysis. Results: Multiple HTO plannings by two medical investigators using standardized procedures showed only minimal differences. In the 3D-simulation, each 10° rotation of the hinge axis resulted in a 1.7° significant increase in slope. Tilting the osteotomy plane by 10° resulted in significant torsional changes of 2°, in addition to minor but significant changes in the medial proximal tibial angle (MPTA). Conclusion: Standardized 3D-planning of the HTO can be performed with high reliability using two-observer planning. 3D-simulations suggest that control of the osteotomy plane is highly relevant to avoid unintended changes in the resulting anatomy, but this can be a helpful tool to modify specific angles in different pathologies in the HTO.

Treatment Challenges in Multiple Sclerosis - A Continued Role for Glatiramer Acetate?

Earlier diagnosis, access to disease-modifying therapies (DMTs), and improved supportive care have favorably altered the disease course of multiple sclerosis (MS), leading to an improvement in long-term outcomes for people with MS (PwMS). This success has changed the medical characteristics of the population seen in MS clinics. Comorbidities and the accompanying polypharmacy, immune senescence, and the growing number of approved DMTs make selecting the optimal agent for an individual patient more challenging. Glatiramer acetate (GA), a moderately effective DMT, interacts only minimally with comorbidities, other medications, or immune senescence. We describe here several populations in which GA may represent a useful treatment option to overcome challenges due to advanced age or comorbidities (e.g., hepatic or renal disease, cancer). Further, we weigh GA's potential merits in other settings where PwMS and their neurologists must base treatment decisions on factors other than selecting the most effective DMT, e.g., family planning, conception and pregnancy, or the need for vaccination.

Selective chiroptical sensing of D/L-cysteine.

A chromophoric bifunctional probe design that allows selective chiroptical sensing of cysteine in aqueous solution is introduced. The common need for chiral HPLC separation is eliminated which expedites and simplifies the sample analysis while reducing solvent waste. Screening of the reaction between six phenacyl bromides and the enantiomers of cysteine showed that cyclization to an unsaturated thiomorpholine scaffold coincides with characteristic UV and CD effects, in particular when the reagent carries a proximate auxochromic nitro group. The UV changes and CD inductions were successfully used for determination of the absolute configuration, enantiomeric composition and total concentration of 18 test samples. This assay is highly selective for free cysteine while other amino acids, cysteine derived small peptides and biothiols do not interfere with the chiroptical signal generation.

VisQA: X-raying Vision and Language Reasoning in Transformers.

Visual Question Answering systems target answering open-ended textual questions given input images. They are a testbed for learning high-level reasoning with a primary use in HCI, for instance assistance for the visually impaired. Recent research has shown that state-of-the-art models tend to produce answers exploiting biases and shortcuts in the training data, and sometimes do not even look at the input image, instead of performing the required reasoning steps. We present VisQA, a visual analytics tool that explores this question of reasoning vs. bias exploitation. It exposes the key element of state-of-the-art neural models - attention maps in transformers. Our working hypothesis is that reasoning steps leading to model predictions are observable from attention distributions, which are particularly useful for visualization. The design process of VisQA was motivated by well-known bias examples from the fields of deep learning and vision-language reasoning and evaluated in two ways. First, as a result of a collaboration of three fields, machine learning, vision and language reasoning, and data analytics, the work lead to a better understanding of bias exploitation of neural models for VQA, which eventually resulted in an impact on its design and training through the proposition of a method for the transfer of reasoning patterns from an oracle model. Second, we also report on the design of VisQA, and a goal-oriented evaluation of VisQA targeting the analysis of a model decision process from multiple experts, providing evidence that it makes the inner workings of models accessible to users.

Palladium and Nickel Catalyzed Suzuki Cross-Coupling with Alkyl Fluorides.

Suzuki cross-coupling of benzylic and unactivated aliphatic fluorides with aryl- and alkenylboronic acids has been achieved via mechanistically distinct Pd and Ni catalyzed pathways that outperform competing protodeboronation, ß-hydride elimination, and homocoupling processes. The utility is demonstrated with more than 20 examples including heterocyclic structures, 1,1-disubstituted and trans-1,2-disubstituted alkenes, and by the incorporation of acetonitrile into functionalized (hetero)arenes.

Salient objects dominate the central fixation bias when orienting toward images.

Short-latency saccades are often biased toward salient objects or toward the center of images, for example, when inspecting photographs of natural scenes. Here, we measured the contribution of salient objects and central fixation bias to visual selection over time. Participants made saccades to images containing one salient object on a structured background and were instructed to either look at (i) the image center, (ii) the salient object, or (iii) at a cued position halfway in between the two. Results revealed, first, an early involuntary bias toward the image center irrespective of strategic behavior or the location of objects in the image. Second, the salient object bias was stronger than the center bias and prevailed over the latter when they directly competed for visual selection. In a second experiment, we tested whether the center bias depends on how well the image can be segregated from the monitor background. We asked participants to explore images that either did or did not contain a salient object while we manipulated the contrast between image background and monitor background to make the image borders more or less visible. The initial orienting toward the image was not affected by the image-monitor contrast, but only by the presence of objects-with a strong bias toward the center of images containing no object. Yet, a low image-monitor contrast reduced this center bias during the subsequent image exploration.

Total Splenectomy for a Giant Isolated Splenic Hydatid Cyst Compressing the Abdominal Viscera: A Case Report.

BACKGROUND Extrahepatic and extrapulmonary localizations of cystic echinococcosis (CE) are rare and the incidence of splenic involvement is seen in 1.0% to 3.3% of all cases in the endemic areas of the Middle East and Asia. The diagnostic pathway consists of a detailed travel history, physical examination, abdominal ultrasonography, computed tomography, and serological tests. The efficacy of perioperative administration of albendazole (400 mg twice a day) has been proven; however, the appropriate surgical procedure for the treatment of giant, centrally located splenic hydatid cysts remains controversial. CASE REPORT We present the case of a 49-year-old woman referred to our hospital for a suspected isolated splenic hydatid cyst causing a compression of the right kidney, stomach, and the tail of the pancreas. She reported chronic pain in the left upper quadrant and a history of contact with animals. She underwent open splenectomy via a medial to lateral approach to minimize manipulation of the spleen. In addition, she received perioperative parasitostatic drug therapy with albendazole. The postoperative period was uneventful and the histologic analysis confirmed the diagnosis. CONCLUSIONS The spleen is a rare location for isolated CE, especially in non-endemic areas and must be considered in the differential diagnosis of splenic cystic masses. Surgical resection remains the most effective treatment that completely resolves this condition. A comparison of randomized trials is needed to compare the recurrence rates between splenectomy and spleen-preserving procedures in the treatment of giant splenic hydatid cysts.

Chiroptical sensing of homocysteine.

The cyclization reaction between ortho-phthalaldehyde and l-homocysteine coincides with the generation of a pronounced positive CD signal at approximately 335 nm. Under identical conditions, other amino acids including cysteine produce very weak CD responses. This unusual substrate specificity allows accurate chiroptical analysis of the enantiomeric composition of homocysteine samples in the presence of cysteine without the need for time-consuming chromatographic separation. This significantly simplifies and speeds up ee determination at reduced solvent waste production.

Cancellous allogenic and autologous bone grafting ensure comparable tunnel filling results in two-staged revision ACL surgery.

OBJECTIVES: Patients with recurrent instability after anterior cruciate ligament (ACL) reconstruction often present with enlarged or misplaced tunnels and bone grafting is required prior to the actual revision reconstruction. Autologous bone grafting features limited quantity and donor site morbidity. These problems may be eliminated utilizing cancellous bone allografts, but their efficiency and reliability have not been investigated systematically. The aim of the present study was to compare tunnel filling rates attained by utilizing either allogenic or autologous cancellous bone grafts. MATERIALS AND METHODS: A total of 103 consecutive patients were enrolled retrospectively. All patients suffered from recurrent instability and underwent either allogenic or autologous cancellous bone grafting. Computed tomography (CT) was carried out before and after the bone grafting procedure. Based on preoperative CT scans, positioning and maximum diameter of the femoral and tibial tunnels were determined. Tunnel filling rates were calculated as a ratio of pre- and postoperative tunnel volumes. Primary outcome was the tibial tunnel filling rate. Femoral filling rates and density of the grafted bone were assessed secondarily. RESULTS: Preoperative CT scans revealed no significant differences between the two groups regarding distribution of misplacement and widening of the femoral or tibial tunnel. Postoperative CT scans were conducted after an interval of 5.2 months. Tunnel filling rates of 74.5% (± 14.3) femoral and 85.3% (± 10.3) tibial were achieved in the allogenic compared to 74.3% (± 15.9) femoral and 84.9% (± 9.4) tibial in the autologous group. With p values of 0.85 at the femur and 0.83 at the tibia, there were no significant differences between the groups. The density of the grafted bone revealed significantly higher values in the allogenic group. CONCLUSIONS: Utilizing cancellous bone allografts in two-staged revision ACL surgery provides for sufficient and reproducible filling of enlarged or misplaced tunnels. The filling rates are comparable to those achieved with autologous bone grafting. Advantages of allografts are the unrestricted quantity and the absence of any harvesting procedure.

Machine Learning-Based Classification of the Health State of Mice Colon in Cancer Study from Confocal Laser Endomicroscopy.

In this article, we address the problem of the classification of the health state of the colon's wall of mice, possibly injured by cancer with machine learning approaches. This problem is essential for translational research on cancer and is a priori challenging since the amount of data is usually limited in all preclinical studies for practical and ethical reasons. Three states considered including cancer, health, and inflammatory on tissues. Fully automated machine learning-based methods are proposed, including deep learning, transfer learning, and shallow learning with SVM. These methods addressed different training strategies corresponding to clinical questions such as the automatic clinical state prediction on unseen data using a pre-trained model, or in an alternative setting, real-time estimation of the clinical state of individual tissue samples during the examination. Experimental results show the best performance of 99.93% correct recognition rate obtained for the second strategy as well as the performance of 98.49% which were achieved for the more difficult first case.

The value of elbow arthroscopy in diagnosing and treatment of radial head fractures.

BACKGROUND: Surgical treatment of radial head fractures is increasingly performed arthroscopically. These fractures often feature concomitant injuries to the elbow joint, which may be under-diagnosed in the radiological examinations. Little is known about the diagnostic value of arthroscopy, the treatment options that arise from arthroscopically assisted fracture fixation and clinical results. We hypothesized that arthroscopy can detect additional concomitant injuries and simultaneously expands the therapeutic options. Therefore aim of this study was to compare arthroscopic and radiologic findings, to assess the distinct arthroscopic procedures and to follow up on the clinical outcomes. METHODS: Twenty patients with radial head fractures were retrospectively included in two study centers. All patients underwent elbow arthroscopy due to at least one of the following suspected concomitant injuries: osteochondral lesions of the humeral capitellum, injuries of the collateral ligaments or loose joint bodies. Preoperative radiological findings were compared to arthroscopic findings. Afterwards, arthroscopic treatment options and clinical outcomes were assessed. RESULTS: Arthroscopic findings led to revision of the classified fracture type in 70% (p = 0.001) when compared to preoperative conventional radiographs (CR) and in 9% (p = 0.598) when compared to computed tomography (CT) or magnetic resonance imaging (MRI). Diagnosis of loose bodies was missed in 60% (p < 0.001) of the CR and in 18% (p = 0.269) of the CT/MRI scans. Osteochondral lesions were not identified in 94% (p < 0.001) of the CR and in 27% (p = 0.17) of the CT/MRI scans. Percutaneous screw fixation was performed in 65% and partial radial head resection in 10%. Arthroscopy revealed elbow instability in 35%, leading to lateral collateral ligament reconstruction. After a mean follow up of 41.4 ± 3.4 months functional outcome was excellent in all cases (DASH-Score 0.6 ± 0.8; MEPI-Score 98.5 ± 2.4; OES-Score 47.3 ± 1.1). CONCLUSIONS: Elbow arthroscopy has a significant diagnostic value in radial head fractures when compared to standard radiological imaging. Although statistically not significant, arthroscopy also revealed concomitant injuries in patients that presented with an uneventful MRI/CT. Furthermore, all intraarticular findings could be treated arthroscopically allowing for excellent functional outcomes. TRIAL REGISTRATION: Institutional Review Board University of Munich (LMU), Trial Number 507-14.

Augmentation of plate osteosynthesis for proximal humeral fractures: a systematic review of current biomechanical and clinical studies.

INTRODUCTION: Secondary dislocation due to loss of fixation is the most common complication after plate fixation of proximal humeral fractures. A wide range of different techniques for augmentation has been described to improve the primary and secondary stability. Nevertheless, comparative analyses on the specific advantages and limitations are missing. Therefore, the aim of the present article was to systematically review and evaluate the current biomechanical and clinical studies. MATERIALS AND METHODS: The databases of PubMed and EMBASE were comprehensively searched for studies on augmentation techniques for proximal humeral fractures using defined search terms. Subsequently, all articles identified were screened for eligibility and subdivided in either clinical or biomechanical studies. Furthermore, the level of evidence and study quality were assessed according the Oxford Centre for Evidence-Based Medicine and the Coleman Methodology Score, respectively. RESULTS: Out of 2788, 15 biomechanical and 30 clinical studies were included. The most common techniques were structural allogenic or autologous bone grafting to enhance the medial support, metaphyseal void filling utilizing synthetic bone substitutes or bone grafts, and screw-tip augmentation with bone cement. Biomechanical data were available for structural bone grafting to enhance the medial support, void filling with synthetic bone substitutes, as well as for screw-tip augmentation. Clinical evidence ranged from level II-IV and study quality was 26-70/100 points. Only one clinical study was found investigating screw-tip augmentation. All studies included revealed that any kind of augmentation positively enhances mechanical stability, reduces the rate of secondary dislocation, and improves patients' clinical outcome. None of the studies showed relevant augmentation-associated complication rates. CONCLUSIONS: Augmentation of plate fixation for proximal humeral fractures seems to be a reliable and safe procedure. All common techniques mechanically increase the constructs' stability. Clinically evaluated procedures show reduced complication rates and improved patient outcomes. Augmentation techniques seem to have the highest significance in situations of reduced bone mineral density and in high-risk fractures, such as 4-part fractures. However, more high-quality and comparative clinical trials are needed to give evidence-based treatment recommendations.

Optical Chirality Sensing with a Stereodynamic Aluminum Biphenolate Probe.

The determination of the enantiopurity and the concentration of chiral compounds by chiroptical sensing with molecular probes is increasingly attractive for high-throughput screening applications including streamlined asymmetric reaction development. In this study, we use stereodynamic aluminum biphenolate complexes for quantitative ee and concentration analysis of amino alcohols and α-hydroxy acids. An important feature of the tropos biphenolate ligand used is the presence of a phenylacetylene antenna for optimal chirality recognition and CD/UV responses at high wavelengths. The complexation-driven chirality amplification yields strong CD signals, which allows quantitative chiroptical sensing with good accuracy. We show that aluminate biphenolate sensors can exhibit linear and nonlinear correlations between the induced CD signals and the enantiomeric composition or concentration of the chiral substrate.