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Hyperkalaemia is one of the most common electrolyte disorders in patients with cardiovascular disease (CVD). The true burden of hyperkalaemia in the real-world setting can be difficult to assess, but in population-based cohort studies up to 4 in 10 patients developed hyperkalaemia. In addition to drugs interfering with potassium metabolism and food intake, several conditions can cause or worsen hyperkalaemia, such as advanced age, diabetes, and chronic kidney disease. Mortality, cardiovascular morbidity, and hospitalisation are higher in patients with hyperkalaemia. Hyperkalaemia represents a major contraindication or a withholding cause for disease-modifying therapies like renin–angiotensin–aldosterone inhibitors (RAASi), mainly mineralocorticoid receptor antagonists. Hyperkalaemia can be also classified as acute and chronic, according to the onset. Acute hyperkalaemia is often a life-threatening emergency requiring immediate treatment to avoid lethal arrhythmias. Therapy goal is cell membrane stabilisation by calcium administration, cellular intake, shift of extracellular potassium to the intracellular space (insulin, beta-adrenergic agents, sodium bicarbonate), and increased elimination with diuretics or dialysis. Chronic hyperkalaemia was often managed with dietary counselling to prevent potassium-rich food intake and tapering of potassium-increasing drugs, mostly RAASi. Sodium polystyrene sulphonate, a potassium binder, was the only therapeutic option. Recently, new drugs such as patiromer and sodium zirconium cyclosilicate give new opportunities for the treatment of hyperkalaemia, as they proved to be safe, well tolerated, and effective. Aim of this review is to describe the burden of hyperkalaemia in cardiovascular patients, its direct and indirect effects, and the therapeutic options now available in the acute and chronic setting.

In the context of biomaterials, small-molecules and drugs testing, intravital microscopy allows to quantify in-vivo the immune reaction, reducing the number of laboratory animals required to statistically validate the product. However, fluorescence microscopy is affected by limited tissue penetration due to light scattering and by optical aberrations, induced on focused beams, by the animal tissue surrounding the implant. In this framework, we developed a system of microlenses coupled to microscaffolds, both incorporated in a miniaturized imaging window. The chip is designed to act as an in-situ microscope objective with the aim to overcome the restrictions of in-vivo imaging (i.e. spherical aberrations) and to allow multiple biological observations in the same animal (by including fluorescent beacons). The device is fabricated by two-photon polymerizing a biocompatible photoresist called SZ2080. The microlenses are manufactured by the concentric polar scanning of the laser beam to realize their outer surface, followed by the UV bulk polymerization of their inner SZ2080. We preliminarily characterized the imaging capabilities of our implantable system on live cells cultured on flat substrates and 3D microscaffolds by coupling it to low magnification objectives. The microlenses optical quality is sufficient to induce non-linear excitation and collect two-photon excitation images with the same level of laser intensity and signal-to-noise ratio. Remarkably, they allow to efficiently excite the fluorescence of labelled human fibroblasts collecting high resolution magnified images. These results will open the way to the application of implanted micro-optics for the real-time and continuous in-vivo observation of complex biological processes.

The possibility to fabricate microstructures to be used in the medical field is a reality. Further steps in this direction consist in the fabrication of active microstructures for implants and/or for cellular treatments. Two major areas of interest will be briefly treated here. The first is the one of stimulus-responsive optical polymers, especially hydrogels, that can be shaped by means of laser 3D printing and ablation. These can be used for thermal stimulation, energy transduction and sensing. The composition of these polymeric blends is an essential parameter to tune their properties as actuators and/or sensing platforms and to determine the elasto-mechanical characteristics of the printed hydrogel. A second field of interest is the microfabrication of rigid microstructures that can stand the tissue-induced stresses in implants. The increasing demand of microdevices for nanomedicine and personalized medicine has fostered the quest for an efficient combination of composite and hybrid photo-responsive materials and digital micro/nano-manufacturing. Existing works have exploited multiphoton laser photo-polymerization to obtain fine 3D microstructures in hydrogels in an additive manufacturing approach or exploited laser ablation of preformed hydrogels to carve 3D cavities. The aim of this report is to provide a short overview of the basics of photo-polymerization induced by two-photon excitation and to discuss two case studies. In the first one, we discuss the most recent and prominent results in the field of multiphoton laser direct writing of biocompatible hydrogels that embed active nanomaterials not interfering with the writing process and endowing the biocompatible microstructures with physically or chemically activable features such as photo-thermal activity, chemical swelling and chemical sensing. In the second case, we outline the fabrication steps and the first tests of a novel chip which aims at enabling longitudinal studies of the reaction to the biomater

Intravital microscopy windows for in vivo observation of tissue are desirable in many biomedical fields, from immunology to the assessment of the foreign body reaction to biomaterials. Moreover, they allow one to reduce the number of animals required to statistically validate biomaterials if compared with traditional histopathological analyses of animal biopsies [1,2].

We report new methods of 2 photon polymerization of microlenses with high numerical aperture, large diameter and good optical quality. We characterize the aberrations of these lenses that, coupled to raster scanning optical microscopes, allow two-photon excitation imaging of cells. In-vivo non-linear imaging will be also discussed, opening the possibility to use these micro-lenses in implants for the continuous inspection of biological dynamics in vivo.

Non-linear excitation microscopy offers several advantages for in-vivo imaging compared to conventional confocal techniques. However, tissue penetration can still be an issue due to scattering and spherical aberrations induced on focused beams by the tissue. The use of low numerical aperture objectives to pass through the outer layers of the skin, together with high dioptric power microlenses implanted in-vivo close to the observation volume, can be beneficial to the reduction of optical aberrations. Here, Fibroblast cell culture plano-convex microlenses to be used for non-linear imaging of biological tissue are developed and tested. The microlenses can be used as single lenses or multiplexed in an array. A thorough test of the lenses wavefront is reported together with the modulation transfer function and wavefront profile. Magnified fluorescence images can be retrieved through the microlenses coupled to commercial confocal and two-photon excitation scanning microscopes. The signal-to-noise ratio of the images is not substantially affected by the use of the microlenses and the magnification can be adjusted by changing the relative position of the microlens array to the microscope objective and the immersion medium. These results are opening the way to the application of implanted micro-optics for optical in-vivo inspection of biological processes.

We report new methods of 2 photon polymerization of microlenses with high numerical aperture, large diameter and good optical quality. We characterize the aberrations of these lenses that, coupled to raster scanning optical microscopes, allow two-photon excitation imaging of cells. In-vivo non-linear imaging will be also discussed, opening the possibility to use these micro-lenses in implants for the continuous inspection of biological dynamics in vivo.

Surgical excision followed by histopathological examination is the gold standard for melanoma screening. However, the color-based inspection of hematoxylin-and-eosin-stained biopsies does not provide a space-resolved quantification of the melanin content in melanocytic lesions. We propose a non-destructive photo-thermal imaging method capable of characterizing the microscopic distribution and absolute concentration of melanin pigments in excised melanoma biopsies. By exploiting the photo-thermal effect primed by melanin absorption of visible laser light we obtain label-free super-resolution far-infrared thermal images of tissue sections where melanin is spatially mapped at sub-diffraction 40-µm resolution. Based on the finite-element simulation of the full 3D heat transfer model, we are able to convert temperature maps into quantitative images of the melanin molar concentration on B16 murine melanoma biopsies, with 4·10−4 M concentration sensitivity. Being readily applicable to human melanoma biopsies in combination with hematoxylin-and-eosin staining, the proposed approach could complement traditional histopathology in the characterization of pigmented lesions ex-vivo.

The current protocols for biocompatibility assessment of biomaterials, based on histopathology, require the sacrifice of a huge number of laboratory animals with an unsustainable ethical burden and remarkable cost. Intravital microscopy techniques can be used to study implantation outcomes in real time though with limited capabilities of quantification in longitudinal studies, mainly restricted by the light penetration and the spatial resolution in deep tissues. We present the outline and first tests of a novel chip which aims to enable longitudinal studies of the reaction to the biomaterial implant. The chip is composed of a regular reference microstructure fabricated via two-photon polymerization in the SZ2080 resist. The geometrical design and the planar raster spacing largely determine the mechanical and spectroscopic features of the microstructures. The development, in-vitro characterization and in vivo validation of the Microatlas is performed in living chicken embryos by fluorescence microscopy 3 and 4 days after the implant; the quantification of cell infiltration inside the Microatlas demonstrates its potential as novel scaffold for tissue regeneration.

Background: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. Methods: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. Results: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge