Effective exosomes reduction in hypercholesterinemic patients suffering from cardiovascular diseases by lipoprotein apheresis: Exosomes apheresis.

INTRODUCTION: Extracellular vesicles (EVs) have been identified as playing a role in atherosclerosis. METHODS: A group of 37 hypercholesterolemic patients with atherosclerotic cardiovascular diseases (ASCVD) and 9 patients requiring hemodialysis (HD) were selected for the study. RESULTS: EVs were comparably reduced by various LA methods (Thermo: 87.66% ± 3.64, DALI: 87.96% ± 4.81, H.E.L.P.: 83.38% ± 11.98; represented as SEM). However, LDL-C (66%; 55%; 75%) and Lp(a) (72%; 67%; 79%) were less effectively reduced by DALI. There was no significant difference in the reduction of EVs when comparing different techniques, such as hemoperfusion (DALI; n = 13), a precipitation (H.E.L.P.; n = 5), and a double filtration procedure (Thermofiltration; n = 19). Additionally, no effect of hemodialysis on EVs reduction was found. CONCLUSIONS: The study suggests that EVs can be effectively removed by various LA procedures, and this effect appears to be independent of the specific LA procedure used, as compared to hemodialysis.

Free Flap Reconstruction of Sternal Defects after Cardiac Surgery: An Algorithmic Approach for Dealing with Sparse Recipient Vessels.

Background: Sparsity of recipient vessels poses a challenge for microsurgical free flap reconstruction of sternal defects following deep sternal wound infection after cardiac surgery. Methods: From January 2013, a standardized algorithm for dealing with sparse recipient vessels was strictly followed. In this retrospective study including 75 patients, we compared operative details, surgical complications, and reconstructive outcomes of patients treated according to this algorithm (group A: January 2013-May 2021; n = 46) with a historical control group (group B: January 2000-December 2012, n = 29). Results: The left internal mammary artery had been harvested for arterial bypass grafting in 40 of 46 cases (87%) in group A and in all cases in group B. The right internal mammary artery (RIMA) and right internal mammary vein (RIMV) were the first choice as recipient vessels. In case of unsuitability of the RIMV, a right cephalic vein (CV) turndown was used for venous outflow. If both RIMA and RIMV proved insufficient, a single-stage arterio-venous loop (AVL) between the CV and subclavian artery (CV-SA AVL), CV and thoracoacromial artery (CV-TA AVL), or subclavian artery and subclavian vein (SA-SV AVL) was established. The algorithmic approach significantly reduced partial flap necrosis [group A: n = 3 (7%) versus group b: n = 7 (24%); P = 0.04], and overall operation time [group A: 360 ±â€…88 min versus group B: 415 ±â€…80 min; P = 0.01]. Conclusions: Standardized approaches improve clinical outcomes in microsurgical free flap sternal reconstruction after cardiac surgery.

Radium-223 in women with hormone receptor-positive bone-metastatic breast cancer receiving endocrine therapy: pooled analysis of two international, phase 2, randomized, double-blind, placebo-controlled trials.

BACKGROUND: Most women with advanced breast cancer have skeletal metastases. Radium-223 is an alpha-emitting radionuclide that selectively targets areas of bone metastases. METHODS: Two double-blind, placebo-controlled studies of radium-223 were conducted in women with hormone receptor-positive (HR+), bone-predominant metastatic breast cancer. All patients received endocrine therapy (ET), as a single agent of the investigator's choice (Study A) or exemestane + everolimus (Study B). Patients were randomized to receive radium-223 (55 kBq/kg) or placebo intravenously every 4 weeks for six doses. Accrual was halted following unblinded interim analyses per protocol amendments, and both studies were terminated. We report pooled analyses of symptomatic skeletal event-free survival (SSE-FS; primary endpoint), radiologic progression-free survival (rPFS) and overall survival (OS; secondary), and time to bone alkaline phosphatase (ALP) progression (exploratory). RESULTS: In total, 382 patients were enrolled, and 196 SSE-FS events (70% planned total) were recorded. Hazard ratios (95% confidence intervals) and nominal p values for radium-223 + ET versus placebo + ET were: SSE-FS 0.809 (0.610-1.072), p = 0.1389; rPFS 0.956 (0.759-1.205), p = 0.7039; OS 0.889 (0.660-1.199), p = 0.4410; and time to bone ALP progression 0.593 (0.379-0.926), p = 0.0195. Radium-223- or placebo-related treatment-emergent adverse events were reported in 50.3% versus 35.1% of patients (grade 3/4: 25.7% vs. 8.5%), with fractures/bone-associated events in 23.5% versus 23.9%. CONCLUSIONS: In patients with HR+ bone-metastatic breast cancer, numeric differences favoring radium-223 + ET over placebo + ET for the primary SSE-FS endpoint were suggestive of efficacy, in line with the primary outcome measure used in the underlying phase 2 studies. No similar evidence of efficacy was observed for secondary progression or survival endpoints. Adverse events were more frequent with radium-223 + ET versus placebo + ET, but the safety profile of the combination was consistent with the safety profiles of the component drugs. Clinical trial registration numbers Study A: NCT02258464, registered October 7, 2014. Study B: NCT02258451, registered October 7, 2014.

Near-Field Observation of the Photonic Spin Hall Effect.

The photonic spin Hall effect, referring to the spatial separation of photons with opposite spins due to spin-orbit interactions, has enabled potential for various spin-sensitive applications and devices. Here, using scattering-type near-field scanning optical microscopy, we observe spin-orbit interactions introduced by a subwavelength semiring antenna integrated in a plasmonic circuit. Clear evidence of unidirectional excitation of surface plasmon polaritons is obtained by direct comparison of the amplitude- and phase-resolved near-field maps of the plasmonic nanocircuit under excitation with photons of opposite spin states coupled to a plasmonic nanoantenna. We present details of the antenna design and experimental methods to investigate the spatial variation of complex electromagnetic fields in a spin-sensitive plasmonic circuit. The reported findings offer valuable insights into the generation, characterization, and application of the photonic spin Hall effect in photonic integrated circuits for future and emerging spin-selective nanophotonic systems.

Microporous Polylactic Acid Scaffolds Enable Fluorescence-Based Perfusion Imaging of Intrinsic In Vivo Vascularization.

In vivo tissue engineering (TE) techniques like the AV loop model provide an isolated and well-defined microenvironment to study angiogenesis-related cell interactions. Functional visualization of the microvascular network within these artificial tissue constructs is crucial for the fundamental understanding of vessel network formation and to identify the underlying key regulatory mechanisms. To facilitate microvascular tracking advanced fluorescence imaging techniques are required. We studied the suitability of microporous polylactic acid (PLA) scaffolds with known low autofluorescence to form axial vascularized tissue constructs in the AV loop model and to validate these scaffolds for fluorescence-based perfusion imaging. Compared to commonly used collagen elastin (CE) scaffolds, the total number of vessels and cells in PLA scaffolds was lower. In detail, CE-based constructs exhibited significantly higher vessel numbers on day 14 and 28 (d14: 316 ± 53; d28: 610 ± 74) compared to the respective time points in PLA-based constructs (d14: 144 ± 18; d28: 327 ± 34; each p < 0.05). Analogously, cell counts in CE scaffolds were higher compared to corresponding PLA constructs (d14: 7661.25 ± 505.93 and 5804.04 ± 716.59; d28: 11211.75 + 1278.97 and 6045.71 ± 572.72, p < 0.05). CE scaffolds showed significantly higher vessel densities in proximity to the main vessel axis compared to PLA scaffolds (200-400 µm and 600-800 µm on day 14; 400-1000 µm and 1400-1600 µm on day 28). CE scaffolds had significantly higher cell counts on day 14 at distances from 800 to 2000 µm and at distances from 400 to 1600 µm on day 28. While the total number of vessels and cells in PLA scaffolds were lower, both scaffold types were ideally suited for axial vascularization techniques. The intravascular perfusion of PLA-based constructs with fluorescence dye MHI148-PEI demonstrated dye specificity against vascular walls of low- and high-order branches as well as capillaries and facilitated the fluorescence-based visualization of microcirculatory networks. Fluorophore tracking may contribute to the development of automated quantification methods after 3D reconstruction and image segmentation. These technologies may facilitate the characterization of key regulators within specific subdomains and add to the current understanding of vessel formation in axially vascularized tissue constructs.

Electrical programmable multilevel nonvolatile photonic random-access memory.

Photonic Random-Access Memories (P-RAM) are an essential component for the on-chip non-von Neumann photonic computing by eliminating optoelectronic conversion losses in data links. Emerging Phase-Change Materials (PCMs) have been showed multilevel memory capability, but demonstrations still yield relatively high optical loss and require cumbersome WRITE-ERASE approaches increasing power consumption and system package challenges. Here we demonstrate a multistate electrically programmed low-loss nonvolatile photonic memory based on a broadband transparent phase-change material (Ge2Sb2Se5, GSSe) with ultralow absorption in the amorphous state. A zero-static-power and electrically programmed multi-bit P-RAM is demonstrated on a silicon-on-insulator platform, featuring efficient amplitude modulation up to 0.2 dB/µm and an ultralow insertion loss of total 0.12 dB for a 4-bit memory showing a 100× improved signal to loss ratio compared to other phase-change-materials based photonic memories. We further optimize the positioning of dual microheaters validating performance tradeoffs. Experimentally we demonstrate a half-a-million cyclability test showcasing the robust approach of this material and device. Low-loss photonic retention-of-state adds a key feature for photonic functional and programmable circuits impacting many applications including neural networks, LiDAR, and sensors for example.

Enhancing Focusing and Defocusing Capabilities with a Dynamically Reconfigurable Metalens Utilizing Sb2Se3 Phase-Change Material.

Metalenses are emerging as an alternative to digital micromirror devices (DMDs), with the advantages of compactness and flexibility. The exploration of metalenses has ignited enthusiasm among optical engineers, positioning them as the forthcoming frontier in technology. In this paper, we advocate for the implementation of the phase-change material, Sb2Se3, capable of providing swift, reversible, non-volatile focusing and defocusing within the 1550 nm telecom spectrum. The lens, equipped with a robust ITO microheater, offers unparalleled functionality and constitutes a significant step toward dynamic metalenses that can be integrated with beamforming applications. After a meticulously conducted microfabrication process, we showcase a device capable of rapid tuning (0.1 MHz level) for metalens focusing and defocusing at C band communication, achieved by alternating the PCM state between the amorphous and crystalline states. The findings from the experiment show that the device has a high contrast ratio for switching of 28.7 dB.

Self-Powered Sb2Te3/MoS2 Heterojunction Broadband Photodetector on Flexible Substrate from Visible to Near Infrared.

Van der Waals (vdWs) heterostructures, assembled by stacking of two-dimensional (2D) crystal layers, have emerged as a promising new material system for high-performance optoelectronic applications, such as thin film transistors, photodetectors, and light-emitters. In this study, we showcase an innovative device that leverages strain-tuning capabilities, utilizing a MoS2/Sb2Te3 vdWs p-n heterojunction architecture designed explicitly for photodetection across the visible to near-infrared spectrum. These heterojunction devices provide ultra-low dark currents as small as 4.3 pA, a robust photoresponsivity of 0.12 A W-1, and reasonable response times characterized by rising and falling durations of 0.197 s and 0.138 s, respectively. These novel devices exhibit remarkable tunability under the application of compressive strain up to 0.3%. The introduction of strain at the heterojunction interface influences the bandgap of the materials, resulting in a significant alteration of the heterojunction's band structure. This subsequently shifts the detector's optical absorption properties. The proposed strategy of strain-induced engineering of the stacked 2D crystal materials allows the tuning of the electronic and optical properties of the device. Such a technique enables fine-tuning of the optoelectronic performance of vdWs devices, paving the way for tunable high-performance, low-power consumption applications. This development also holds significant potential for applications in wearable sensor technology and flexible electro-optic circuits.

[State of the art: lipoprotein apheresis]. / State of the Art: Lipoproteinapherese.

Lipoprotein apheresis (LA) is usually a last resort in cardiovascular high-risk patients in the context of secondary prevention after lifestyle measures and maximal pharmacotherapy have failed to prevent the occurrence of new atherosclerotic cardiovascular events (ASCVDE) or to achieve the internationally accepted target values for LDL cholesterol (LDL-C). Patients with homozygous familial hypercholesterolemia (hoFH), in whom myocardial infarctions can occur even in children < 10 years of age without adequate therapy, often owe their survival to LA (used here in primary prevention). Severe hypercholesterolemia (HCH) can often be well controlled with modern potent lipid-lowering agents, including PCSK9 approaches, so that the need for LA has decreased here over the years. In contrast, the number of patients in whom elevation of lipoprotein(a) (Lp(a)) is relevant to atherogenesis is increasing in applications to the apheresis committees of the associations of panel physicians (KV). For this indication, LA is currently the only therapeutic procedure approved by the Federal Joint Committee (G-BA). LA significantly reduces the new occurrence of ASCVDE (comparison with the situation before the start of LA), especially in Lp(a) patients. There are convincing observational studies and a German LA Registry with now 10-year data, but there is no randomized controlled trial. This had been requested by the G-BA in 2008, and a corresponding concept was designed but not accepted by the ethics committee. In addition to the highly effective reduction of atherogenic lipoproteins, many discussed pleiotropic effects of LA itself, the medical rounds and motivating discussions also with the nursing staff, which take place within the weekly LA, certainly contribute to the success of the therapy (steady adjustment of all cardiovascular risk factors, lifestyle measures including smoking cessation, adherence of medication intake). This review article summarizes and discusses the study situation, clinical practical experience as well as the future of LA against the background of the currently rapid development of new pharmacotherapies.

Fat Grafts Show Higher Hypoxia, Angiogenesis, Adipocyte Proliferation, and Macrophage Infiltration than Flaps in a Pilot Mouse Study.

BACKGROUND: Over 137,000 breast reconstructions are performed annually by American Society of Plastic Surgeons (ASPS) members. Vascularized flaps and avascular lipofilling each account for over 33,000 autologous reconstructions. Although clinical and experimental observations suggest biologic differences with diverging effects on locoregional tumor control, comparative animal models are lacking. The authors standardized existing techniques in immunocompetent mice, laying the foundation for in vivo models of autologous breast reconstruction combinable with orthotopic tumor implantations. METHODS: Twenty-five groin flaps and 39 fat grafts were transferred in female BALB/c-mice. Adipocytes were tracked via Hoechst-Calcein-DiI staining ( n = 2 per group), and postoperative volume retentions were compared via magnetic resonance imaging ( n = 3 per group) on days 1, 11, 21, and 31. Proliferation indices, microvessel densities, tissue hypoxia, and macrophage infiltrates were compared via Ki67, CD31, pimonidazole, and hematoxylin-eosin staining on days 5, 10, 15, 20, and 30 ( n = 4 per group). RESULTS: Viable adipocytes were present in both groups. Graft volumes plateaued at 42.7 ± 1.2% versus 81.8 ± 4.0% of flaps ( P < 0.001). Initially, grafts contained more hypoxic cells (day 5: 15.192 ± 1.249 versus 1.157 ± 192; P < 0.001), followed by higher proliferation (day 15: 25.2 ± 1.0% versus 0.0 ± 0.0%; P < 0.001), higher microvessel numbers (day 30: 307.0 ± 13.2 versus 178.0 ± 10.6; P < 0.001), and more pronounced macrophage infiltrates (graded 3 versus 2; P < 0.01). CONCLUSION: This comparative murine pilot study of vascularized flaps versus avascular lipofilling suggests differences in volume retention, proliferation, angiogenesis, hypoxia, and inflammation. CLINICAL RELEVANCE STATEMENT: The biological differences of fat grafting versus flap transfer are not fully understood because no single comparative experimental model has been established to date. The authors present the first comparative small animal model of both techniques, which will allow the gaining of deeper insights into their biological effects.

Beyond cholesterol-pleiotropic effects of lipoprotein apheresis.

Cardiovascular disease is a leading cause of mortality worldwide, which is caused mainly by atherosclerosis, a chronic inflammatory disease of blood vessels. Therefore, atherosclerosis represents a complex disorder, which induces damage or imbalance on different levels: for example, genes, cytokines, lipoproteins, cells, vessels, and organs. Lipoprotein apheresis (LA) is a well-established extracorporeal treatment of severe hyperlipoproteinemia. In addition, LA may have simultaneously crucial effects on many other atherogenic factors during the treatments, for example, as vascular inflammation, rheology, mobilization of adult stem cells and gene expressions in blood or endothelial cells, which will be discussed in this short review. In addition, stable microRNAs besides tissues also appear in extracellular compartments, for example, vessels, involved in atherosclerotic processes, were found to be reduced by LA treatments. In summary, LA represents a complex therapeutic procedure, that provides an ideal tool for the treatment of complex disorders such as atherosclerosis.

The German Lipoprotein Apheresis Registry-Summary of the ninth annual report.

During 2012-2020, 89 German apheresis centers collected retrospective and prospective observational data of 2028 patients undergoing regular lipoprotein apheresis (LA) for the German Lipoprotein Apheresis Registry (GLAR). More than 47 500 LA sessions are documented in GLAR. In 2020, all patients treated with LA showed a high immediate median reduction rate of LDL-C (68.2%, n = 1055) and Lp(a) (72.4%, n = 994). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to 7 years on LA (y + 1 to y + 7). During the first 2 years of LA (y + 1 and y + 2), a MACE reduction of 78% was observed. Current analysis of GLAR data shows very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid lowering medication regular by LA results.

Event- and biostratigraphic evidence for two independent Ries and Steinheim asteroid impacts in the Middle Miocene.

For decades, the Nördlinger Ries and Steinheim Basin in southern Germany have been regarded as a textbook example of a terrestrial impact crater doublet, although the oldest crater lake deposits in both craters suggest a biostratigraphic age difference of ~ 0.5 to 1 Myr. We previously presented stratigraphic arguments that challenged the double impact scenario and favoured a model of two temporally independent impact events in the Mid-Miocene. We here present, for the first time, four localities within a distance of ~ 50-100 km from the Ries and ~ 50-70 km from the Steinheim crater that expose two independent seismite horizons, together unique within the Upper Freshwater Molasse of the North Alpine Foreland Basin, each one featuring impressive water escape structures. The seismite horizons are separated by ~ 10 to 15 m of undisturbed Molasse deposits and, biostratigraphically, by an entire European Land Mammal Zone, thus providing evidence for two independent major seismic events within a time span of ~ 0.5-1 Myr. Both the lower and the upper seismite horizons can be correlated litho- and biostratigraphically with the basal crater lake sediments at the Ries and Steinheim craters, respectively, deposited immediately after the impacts. From a biostratigraphic point of view, the impact event that formed the Steinheim Basin probably occured around 14 Ma, some 0.8 Myr after the ~ 14.81 Ma Ries impact event.

Prepectoral Breast Reconstruction without Acellular Dermal Matrix: Have We Come Full Circle?

Breast reconstruction is an integral part of breast cancer treatment [...].

Novel Insights into the Management of Patients with Very High Cardiovascular Risk Eligible for PCSK9 Inhibitor Treatment: Baseline Findings from the PERI-DYS Study.

AIM: The PERI-DYS study aims to characterize two groups of patients with dyslipidaemia at very high CV risk: PCSK9i receivers and patients qualifying for but not receiving PCSK9i. METHODS: This is an observational study by office-based and clinic-based physicians, mainly cardiologists and other internists in Germany, with data extracted from patient charts. CLINICALTRIALS: gov identifier NCT03110432. RESULTS: A total of 1659 patients were enrolled across 70 sites. The majority of patients (91.0%) were reported as having mixed dyslipidaemia or non-familial or heterozygous familial hypercholesterolemia. At enrolment, 794 (47.9%) of patients were PCSK9i receivers (of these 65.9% ongoing, and 34.1% newly treated within 30 days before their baseline visit). Among PCSK9i receivers, the majority had evolocumab 140 mg (n = 632, 38.1% of total). PCSK9i receivers compared to non-receivers were about 2 years younger and had a lower proportion of males. In terms of comorbidities, they had (statistically significantly) more often CAD, and less often PAD, diabetes mellitus, arterial hypertension and chronic renal disease. The calculated untreated median LDL-C was 187 mg/dl (IQR 127; 270) in ongoing PCSK9i receivers, 212 mg/dl (IQR 132; 277) in newly treated PCSK9i receivers, and 179 mg/dl (IQR 129; 257) in non-receivers. Physician-reported statin intolerance was much more common in the two PCSK9i receiver groups as compared to non-receivers (67.3% versus 15.3%). Consequently, patients in the PCSK9i groups received fewer concomitant statins. Mean total cholesterol (143 vs. 172 mg/dl) and LDL-C (69 vs. 99 mg/dl) were considerably lower in ongoing PCSK9i receivers compared to non-receivers. CONCLUSIONS: PCSK9i receivers are characterized by higher baseline LDL-C and a higher portion of statin intolerance compared to those qualified for but not-receiving PCSK9i treatment. On-treatment, LDL-C was lower in PCSK9i receivers. Ongoing follow-up will determine the prognostic importance of these findings.

Systemically injected bone marrow mononuclear cells specifically home to axially vascularized tissue engineering constructs.

Inducing axial vascularisation of tissue engineering constructs is a well-established method to support tissue growth in large 3-dimensional tissues. Progenitor cell chemotaxis towards axially vascularized tissues has not been well characterized. In a prospective randomized controlled study including 32 male syngeneic Lewis rats we investigated the capability of the axially vascularized constructs to attract systemically injected bone marrow mononuclear cells (BMMNCs). The underlying mechanism for cell homing was investigated focusing on the role of hypoxia and the SDF1-CXCR4-7 axis. Sixteen animals were used as donors for BMMNCs. The other animals were subjected to implantation of a tissue engineering construct in the subcutaneous groin region. These constructs were axially vascularized either via an arteriovenous loop (AVL, n = 6) or via uninterrupted flow-through vessels (non-AVL, n = 10). BMMNCs were labelled with quantum dots (Qdot® 655) and injected 12 days after surgery either via intra-arterial or intravenous routes. 2 days after cell injection, the animals were sacrificed and examined using fluorescence microscopy. The Qdot® 655 signals were detected exclusively in the liver, spleen, AVL constructs and to a minimal extent in the non-AVL constructs. A significant difference could be detected between the number of labelled cells in the AVL and non-AVL constructs with more cells detected in the AVL constructs specially in central zones (p <0.0001). The immunohistological analysis showed a significant increase in the absolute expression of HIF-1 in the AVL group in comparison to the non-AVL group. The PCR analysis confirmed a 1.4-fold increase in HIF-1 expression in AVL constructs. Although PCR analysis showed an enhanced expression of CXCR4 and CXCR7 in AVL constructs, no significant differences in SDF1 expression were detected via immunohistological or PCR analysis. At the examined time point, the AVL constructs can attract BMMNCs in a mechanism probably related to the hypoxia associated with a robust tissue formation.

Maximum Entropy Technique and Regularization Functional for Determining the Pharmacokinetic Parameters in DCE-MRI.

This paper aims to solve the arterial input function (AIF) determination in dynamic contrast-enhanced MRI (DCE-MRI), an important linear ill-posed inverse problem, using the maximum entropy technique (MET) and regularization functionals. In addition, estimating the pharmacokinetic parameters from a DCE-MR image investigations is an urgent need to obtain the precise information about the AIF-the concentration of the contrast agent on the left ventricular blood pool measured over time. For this reason, the main idea is to show how to find a unique solution of linear system of equations generally in the form of [Formula: see text] named an ill-conditioned linear system of equations after discretization of the integral equations, which appear in different tomographic image restoration and reconstruction issues. Here, a new algorithm is described to estimate an appropriate probability distribution function for AIF according to the MET and regularization functionals for the contrast agent concentration when applying Bayesian estimation approach to estimate two different pharmacokinetic parameters. Moreover, by using the proposed approach when analyzing simulated and real datasets of the breast tumors according to pharmacokinetic factors, it indicates that using Bayesian inference-that infer the uncertainties of the computed solutions, and specific knowledge of the noise and errors-combined with the regularization functional of the maximum entropy problem, improved the convergence behavior and led to more consistent morphological and functional statistics and results. Finally, in comparison to the proposed exponential distribution based on MET and Newton's method, or Weibull distribution via the MET and teaching-learning-based optimization (MET/TLBO) in the previous studies, the family of Gamma and Erlang distributions estimated by the new algorithm are more appropriate and robust AIFs.

A Multidisciplinary Approach to Complex Dermal Sarcomas Ensures an Optimal Clinical Outcome.

Primary dermal sarcomas (PDS) belong to a highly clinically, genetically and pathologically heterogeneous group of rare malignant mesenchymal tumours primarily involving the dermis or the subcutaneous tissue. The tumours are classified according to the mesenchymal tissue from which they originate: dermal connective tissue, smooth muscle or vessels. Clinically, PDS may mimic benign soft tissue lesions such as dermatofibromas, hypertrophic scarring, etc. This may cause substantial diagnostic delay. As a group, PDS most commonly comprises the following clinicopathological forms of dermal sarcomas: dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), dermal undifferentiated pleomorphic sarcoma (DUPS), leiomyosarcoma (LMS), and vascular sarcomas (Kaposi's sarcoma, primary angiosarcoma, and radiation-induced angiosarcoma). This clinical entity has a broad spectrum regarding malignant potential; however, local aggressive behaviour in some forms causes surgical challenges. Preoperative, individualised surgical planning with complete free margins is pivotal along with a multidisciplinary approach and collaboration across highly specialised surgical and medical specialties. The present review gives a structured overview of the most common forms of dermal sarcomas including surgical recommendations and examples for advanced reconstructions as well as the current adjunctive medical treatment strategies. Optimal aesthetic and functional outcomes with low recurrence rates can be achieved by using a multidisciplinary approach to complex dermal sarcomas. In cases of extended local tumour invasion in dermal sarcomas, advanced reconstructive techniques can be applied, and the interdisciplinary microsurgeon should be an integral part of the sarcoma board.

A Chirality-Based Quantum Leap.

There is increasing interest in the study of chiral degrees of freedom occurring in matter and in electromagnetic fields. Opportunities in quantum sciences will likely exploit two main areas that are the focus of this Review: (1) recent observations of the chiral-induced spin selectivity (CISS) effect in chiral molecules and engineered nanomaterials and (2) rapidly evolving nanophotonic strategies designed to amplify chiral light-matter interactions. On the one hand, the CISS effect underpins the observation that charge transport through nanoscopic chiral structures favors a particular electronic spin orientation, resulting in large room-temperature spin polarizations. Observations of the CISS effect suggest opportunities for spin control and for the design and fabrication of room-temperature quantum devices from the bottom up, with atomic-scale precision and molecular modularity. On the other hand, chiral-optical effects that depend on both spin- and orbital-angular momentum of photons could offer key advantages in all-optical and quantum information technologies. In particular, amplification of these chiral light-matter interactions using rationally designed plasmonic and dielectric nanomaterials provide approaches to manipulate light intensity, polarization, and phase in confined nanoscale geometries. Any technology that relies on optimal charge transport, or optical control and readout, including quantum devices for logic, sensing, and storage, may benefit from chiral quantum properties. These properties can be theoretically and experimentally investigated from a quantum information perspective, which has not yet been fully developed. There are uncharted implications for the quantum sciences once chiral couplings can be engineered to control the storage, transduction, and manipulation of quantum information. This forward-looking Review provides a survey of the experimental and theoretical fundamentals of chiral-influenced quantum effects and presents a vision for their possible future roles in enabling room-temperature quantum technologies.