Search Results (8,704)

Background/Objectives: Renal transplantation is the treatment of choice for patients with end-stage renal disease. In the last decade, the number of older renal transplant recipients has significantly increased. However, these patients are at a higher risk of developing post-transplant complications. Therefore, identifying the suitable biomarkers to predict which older patients are at risk of complications is crucial. Cellular senescence could provide insights into the increased vulnerability in this population and guide personalized post-transplant care. Methods: This preliminary study involved biopsies from 25 patients with renal allograft rejection and 18 patients without rejection, further divided into older (50–65 years) and younger (29–40 years) groups. Biopsies were collected at different time points after transplantation, and rejection was classified according to the histological Banff 07 criteria. Additionally, immunohistochemistry for the markers of cellular senescence, p27^kip1 and p16^INK4a, was performed. Results: We observed that the number of p27^kip1-positive glomeruli was higher in the older patients with rejection compared to the younger patients with rejection, and a similar pattern was found in the patients without rejection. However, the number of p27^kip1-positive tubules was higher in the older patients with rejection compared to the younger patients with rejection, as well as compared to both the older and younger patients without rejection. Tubular p16^INK4a expression was not significantly different in the older patients with rejection compared to the younger patients with rejection, and the same pattern was observed in the patients without rejection. However, it was increased in the older patients with rejection in comparison to the older patients without rejection. Conclusions: Our preliminary data suggest the strong potential of both p16^INK4a and p27^kip1 as biomarkers of renal graft rejection, particularly in older renal transplant recipients. Full article

Background: The use of microvascular grafts is the gold standard in oral and maxillofacial surgery for the reconstruction of soft tissue and bony and combined defects. Graft loss is one of the most serious complications in the field of reconstructive surgery. A comprehensive analysis of factors influencing this is, therefore, essential. Methods: This hypothesis-generating study analyzed 251 patient cases of oral and maxillofacial surgery at the University Hospital Düsseldorf from 2016 to 2020 regarding patient- and therapy-specific parameters for their impact on graft survival. Results: Statistically significant influencing factors were found among the 80 parameters examined: treatment with antiplatelet medication and a BMI ≥ 24.5 at the time of surgery had a positive influence on graft survival, while existing diabetes mellitus, atrial fibrillation, tracheostomy, and a longer operation time had a statistically relevant negative influence. Conclusions: This work demonstrates the relevance of patient-specific risk stratification and the need for further research to develop a valid risk profile. Identifying high-risk patients with medium-sized defects, where alternatives to microvascular reconstruction are available, appears to be crucial for the clinical outcome. Full article

Peripheral facial paralysis represents a disabling condition with serious psychological and social impact. Patients with peripheral facial paralysis have a disfigurement of the face with loss of harmony and symmetry and difficulties in everyday facial functions such as speaking, drinking, laughing, and closing their eyes, with impairment of their quality of life. This paralysis leads to impairment of facial expression, which represents one of the first means of communication, an important aspect of human interaction. This review aims to explore the reanimation techniques for managing peripheral facial paralysis. An analysis of static and dynamic techniques for facial reanimation is provided, including muscle flaps, nerve grafting techniques, and bioengineering solutions. Each technique showed its benefits and drawbacks; despite several options for facial reanimation, no technique has been detected as the gold standard. Therefore, each patient must be evaluated on an individual basis, considering their medical history, age, expectations, and treatment goals, to find the best and most fitting treatment. Full article

Background: Malignant eyelid tumours present a considerable challenge in the field of ophthalmic oncology, necessitating a combination of precision oncological care and meticulous reconstruction to ensure the preservation of eyelid functionality and the maintenance of facial aesthetics. Method: This study presents a review of the outcomes of 167 patients who underwent eyelid reconstruction following the excision of primary non-melanocytic malignant tumours. The choice of reconstruction technique was dependent on a number of factors, including the stage of the tumour, its location, and the characteristics of the patient. The most commonly used techniques included regional flaps, local flaps, and skin grafts. The most frequently employed reconstruction techniques were forehead flaps (59 cases), simple excisions (38 cases), and Mustarde cheek flaps (16 cases). Result: The postoperative complications, including ectropion, epiphora, and flap necrosis, were recorded. However, no significant correlation was found between the risk of complications and either the location of the tumour or the reconstruction method employed. Despite the complexity of medial canthal and lower eyelid reconstruction, satisfactory aesthetic and functional outcomes were generally achieved. Conclusions: This study emphasises the importance of individualised surgical planning, highlighting the advantages and limitations of various techniques to optimise both the functional and aesthetic results. Full article

The development of biomaterials with gradient surface modification capable of spatially controlled cell adhesion and migration is of great importance for tissue engineering and regeneration. In this study, we proposed a method for the covalent modification of PLA-based materials with a cationic polypeptide (polylysine, PLys) via a thiol-ene click reaction carried out under a light gradient. With this aim, PLA-based films were fabricated and modified with 2–aminoethyl methacrylate (AEMA) as a double bond source. The latter was introduced by reacting pre-formed and activated surface carboxyl groups with the amino group of AEMA. The success of the modification was confirmed by ¹H NMR, Raman and X-ray photoelectron spectroscopy data. A further photoinduced thiol-ene click reaction in the presence of a photosensitive initiator as a radical source was further optimized using cysteine. For grafting of PLys via the thiol-ene click reaction, PLys with a terminal thiol group was synthesized by ring-opening polymerization using Cys(Acm) as an amine initiator. Deprotection of the polypeptide resulted in the formation of free thiol groups of Cys-PLys. Successful gradient grafting of Cys-PLys was evidenced by covalent staining with the fluorescent dye Cy3-NHS. In addition, PLys gradient-dependent adhesion and migration of HEK 293 cells on PLys-PLA-based surfaces was confirmed. Full article

Crigler–Najjar Syndrome (CNS) is a rare genetic disorder caused by mutations in the UGT1A1 gene, leading to impaired bilirubin conjugation and severe unconjugated hyperbilirubinemia. CNS presents in the following forms: CNS type 1 (CNS1), the more severe form with the complete absence of UGT1A1 activity, and CNS type 2 (CNS2), with partial enzyme activity. This narrative review aims to provide a detailed overview of CNS, highlighting its clinical significance and the need for new, more effective treatments. By summarizing current knowledge and discussing future treatments, this article seeks to encourage further research and advancements that can improve outcomes for CNS patients. The literature analysis showed that CNS1 requires aggressive management, including phototherapy and plasmapheresis, but liver transplantation (LT) remains the only definitive cure. The timing of LT is critical, as it must be performed before the onset of irreversible brain damage (kernicterus), making early intervention essential. However, LT poses risks such as graft rejection and lifelong immunosuppression. CNS2 is milder, with patients responding well to phenobarbital and having a lower risk of kernicterus. Recent advancements in gene therapy and autologous hepatocyte transplantation offer promising alternatives to LT. Gene therapy using adeno-associated virus (AAV) vectors has shown potential in preclinical studies, though challenges remain in pediatric applications due to liver growth and pre-existing immunity. Autologous hepatocyte transplantation avoids the risk of rejection but requires further research. These emerging therapies provide hope for more effective and less invasive treatment options, aiming to improve the quality of life for CNS patients and reduce reliance on lifelong interventions. Full article

Purpose: To compare the postoperative complications and clinical outcomes of Descemet membrane endothelial keratoplasty (DMEK) and Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with previous glaucoma filtering surgery. Methods: In this retrospective comparative case series, we analysed postoperative visual acuity and intraocular pressure, graft survival, rate of graft detachment and/or dislocation, number of rebubbling and/or graft repositioning procedures, and graft rejection or failure (primary and secondary). Results: Sixteen eyes with DMEK and 80 eyes with DSAEK with previous glaucoma surgery were studied. The results were recorded at 3 and 12 months postoperatively. No statistically significant differences in postoperative visual acuity were found between the two groups at any stage of the follow-up. Intraocular pressure was lower in the DMEK group at the follow-up stage of 3 (p = 0.0022) and 12 months (p = 0.0480). Visually significant graft detachment was recorded in 31.3% and 22.5% of DMEK and DSAEK cases, respectively (p = 0.4541). All DMEK detachments (n = 5) were managed with slit-lamp rebubbling. Out of 18 graft detachments in the DSAEK group, 2 grafts were observed due to small graft detachment, 6 large graft detachments underwent rebubbling performed in the operating theatre, and 10 eyes needed primary graft repositioning for graft dislocation. Conclusions: DMEK is a feasible option to treat endothelial failure in complex eyes with previous glaucoma surgery. In the DMEK group, visual acuity outcomes and possibly postoperative intraocular pressure control were better compared with the DSAEK group. Full article

Over the past two decades, the development and commercialization of slow-release fertilizers (SRFs) have significantly advanced, with the primary aim of mitigating environmental issues associated with excessive fertilizer use. A range of methodologies, including chemical and physical reactions, incorporation into carriers with porous and layered structures, and coating techniques, have been explored and refined. On the other hand, global challenges such as drought and desertification further underscore the need for SRFs that not only control nutrient release but also improve soil moisture retention. This paper reviews the development and application of eco-friendly starch hydrogels as fertilizer carriers and water retention for SRFs, particularly starch-based superabsorbent polymers (SAPs) produced through grafting copolymerization with acrylamide. This review explores both scientific issues, such as the microstructures and releasing mechanisms of SAPs, and technical development, involving copolymerization technologies, multi-initialization processes, methods of loading fertilizer into hydrogel, etc. Starch, as both a biodegradable and renewable carbohydrate polymer, offers distinct advantages due to its excellent chemical stability and high reactivity. The fabrication techniques of SAPs have been developed from traditional batch polymerization in aqueous solutions to more efficient, solvent-free reactive extrusion. The benefits of SRFs based on SAPs encompass enhanced soil aeration, the prevention of soil deterioration, the minimization of water evaporation, environmental pollution control, reduction in plant mortality, and prolonged nutrient retention within soil. In this review, we summarize the current progress, identify limitations in existing technologies, and propose future research directions to further enhance the performance of starch-based SRFs. Full article

Acute gastrointestinal graft-versus-host disease (GI aGVHD) is a significant and life-threatening complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). Early diagnosis of GI aGVHD is crucial for improving patient outcomes, but it remains a challenge due to the condition’s nonspecific symptoms and the reliance on invasive diagnostic methods, such as biopsies and endoscopic procedures. In recent years, interest in non-invasive diagnostic techniques for graft-versus-host disease has increased, with contrast-enhanced ultrasound (CEUS) being one of them. For this reason, we aimed to examine the potential of ultrasound as a non-invasive, safe, and cost-effective alternative for the early detection and monitoring of GI aGVHD in this review. Our narrative review aims to describe the use of multimodal US that includes conventional US (B-mode and Doppler US) and advanced ultrasound techniques such as CEUS and CRTE for the non-invasive diagnosis of GI GVHD. We browsed several databases, including PubMed, Scopus, Web of Science, and Google Scholar. The search spanned 2000 to the present, focusing on articles written in English that reviewed the use of these imaging techniques in the context of GI GVHD. Following our research, we noticed that CEUS offers several advantages, including the real-time visualization of the gastrointestinal wall, assessment of blood flow, and detailed microvascular analysis—all achieved without the use of ionizing radiation. This feature makes CEUS an appealing option for repeated assessments, which are often necessary in monitoring the progression of GI aGVHD. When used in conjunction with conventional gastrointestinal ultrasound (GIUS), CEUS provides a more comprehensive view of the structural and functional changes occurring in the GI tract, potentially enhancing diagnostic accuracy and allowing for earlier intervention. In comparison to traditional diagnostic methods like tissue biopsy or CT scans, CEUS is less invasive, quicker to perform, and better tolerated by patients, especially those in fragile health following allo-SCT. Its non-invasive nature and ability to provide immediate imaging results make it a valuable tool for clinicians, particularly in settings where minimizing patient discomfort and risk is paramount. However, despite these advantages, there are still gaps in the literature regarding CEUS’s full diagnostic accuracy for GI aGVHD. Further research, including larger clinical trials and comparative studies, is needed to validate CEUS’s role in routine clinical practice and to establish standardized protocols for its use. Nonetheless, CEUS shows considerable potential to transform the diagnostic approach to GI aGVHD by improving early detection, reducing the need for invasive procedures, and ultimately enhancing treatment outcomes for affected patients. Full article

Background: Deviations in serum creatinine (SCr), due to its determination using a Jaffe or an enzymatic method, have an effect on kidney disease detection and staging. It is not yet clear how large this effect is in kidney transplant recipients (KTRs). SCr measurement differences are of particular importance here to evaluate the graft function. Methods: The results of all parallel SCr measurements (Jaffe and enzymatic method) of adult outpatient KTRs in the same serum sample at the University Hospital Essen (Germany) between January 2020 and October 2023 were evaluated. A Bland–Altman plot with 95% limits of agreement (LoA) was used to assess the difference between the Jaffe and the enzymatic SCr (eSCr). For all patients, we used the CKD-EPI 2009 and EKFC formula, and for patients ≥ 70 years, we also used the BIS1 formula for the determination of eGFR. Results: A total of 12,081 parallel SCr measurements from 1243 KTRs were analyzed, where 61% were male and the median age was 53 years. On average, Jaffe SCr was 0.03 mg/dL higher than eSCr (LoA −0.16; 0.21 mg/dL). On average, the eGFR determined by Jaffe SCr was 1.9 mL/min/1.73 m² lower than the eGFR determined by eSCr (LoA −9.5; 5.7 mL/min/1.73 m²). The comparison of eGFR between the two SCr methods revealed a different CKD stage in 1589 (13%) of all analyzed measurements, most frequently between G2/G3a (41%) and G3a/G3b (24%). When using the EKFC and BIS1 formulas, there were approximately the same number of measurements leading to a different CKD stage. Conclusions: In more than every tenth SCr determination in outpatient KTRs, the difference between the Jaffe and enzymatic methods had an influence on the assignment to a CKD stage. This effect was comparably pronounced for all eGFR formulas applied. Full article

Surface-based biosensors have proven to be of particular interest in the monitoring of human pathogens by means of their distinct nucleic acid sequences. Genosensors rely on targeted gene/DNA probe hybridization at the surface of a physical transducer and have been exploited for their high specificity and physicochemical stability. Unfortunately, these sensing materials still face limitations impeding their use in current diagnostic techniques. Most of their shortcomings arise from their suboptimal surface properties, including low hybridization density, inadequate probe orientation, and biofouling. Herein, we describe and compare two functionalization methodologies to immobilize DNA probes on a glass substrate via a thermoresponsive polymer in order to produce genosensors with improved properties. The first methodology relies on the use of a silanization step, followed by PET-RAFT of NIPAM monomers on the coated surface, while the second relies on vinyl sulfone modifications of the substrate, to which the pre-synthetized PNIPAM was grafted to. The functionalized substrates were fully characterized by means of X-ray photoelectron spectroscopy for their surface atomic content, fluorescence assay for their DNA hybridization density, and water contact angle measurements for their thermoresponsive behavior. The antifouling properties were evaluated by fluorescence microscopy. Both immobilization methodologies hold the potential to be applied to the engineering of DNA biosensors with a variety of polymers and other metal oxide surfaces. Full article

Given progressive population ageing and the increase in the number of patients with comorbidities, the management of chronic and/or hard-to-heal wounds (HHWs) nowadays represents a common problem in many clinical settings. In these cases, standard strategies may not be sufficient. Autologous grafting represent the gold standard for permanent wound closure, but is almost never realized when the skin loss is extensive/the patient is young. The grafting of homologous skin/dermal tissue procured from cadaver donors (i.e., allografting) represents the best alternative, especially when the dermal component is lost. This request supports the activities of skin bank establishments (including donor screening, skin procurement, processing, storage, and distribution) that are regulated by specific guidelines and need to continuously meet quality standard requirements. The aim of this work is to both give specific insights of all the procedures implied in allograft preparation as well as an overview of their practical application in the treatment of different HHWs. The particular characteristics of each skin/dermal allograft released by Siena Skin Bank (cryopreserved/glycerol-preserved skin/de-epidermized dermis, acellular lyophilized de-epidermized dermis/reticular dermis) are also discussed. The exemplificative series of HHWs managed in the Dermatology Department of Siena were classified according their etiology into post-traumatic, vascular (arterial/venous/mixed/lymphatic), inflammatory, surgical, and heat/chemical burns. Globally, the clinical advantages obtained include: acceleration of healing process, pain sparing, resistance to bacterial contamination, dermal regeneration (instead of scarring), and better aesthetic–functional outcome. Full article

The endothelin system is reported to play a significant role in glomerular and tubulointerstitial kidney disease. In the kidney, endothelins are produced in mesangial cells and the glomerular basement membrane by the endothelium and podocytes. The endothelin system regulates glomerular function by inducing proliferation, increasing permeability and in effect proteinuria, and stimulating inflammation, tubular fibrosis, and glomerular scarring. Endothelin A receptor antagonists have been proven to delay the progression of chronic kidney disease and play a protective role in immunoglobulin A nephropathy, focal segmental glomerulosclerosis, and diabetic nephropathy. There are several ongoing research studies with ETAR antagonists in nondiabetic nephropathy, Alport disease, vasculitis and scleroderma nephropathy, which results are promising. Some reports suggest that the endothelin system might contribute to ischemia–reperfusion injury, acute graft rejection and deterioration of graft function. Endothelin inhibition in renal transplantation and its influence on graft survival is the future direction needing further research. The most frequent side effects associated with ETAR antagonists is fluid retention. Additionally, it should be considered if selective ETAR antagonists therapy needs to be co-administered with sodium-glucose co-transporter 2 inhibitors, renin–angiotensin–aldosterone inhibitors or diuretics and which patients should be recruited to such treatment to minimize the risk of adverse outcomes. Full article

The sural nerve provides sensory innervation to the skin on the distal posterolateral third of the lower extremity. The morphological variants are characterized by high variability. However, it most commonly arises from a union of the medial sural cutaneous nerve and the peroneal communicating branch of the common fibular nerve. This article overviews the anatomical and clinical significance of the sural nerve. Despite the remarkable development of genetic diagnostics, sural nerve biopsy is still a very important tool to diagnose peripheral neuropathies such as diabetic, vascular and inflammatory neuropathies. Furthermore, the sural nerve is also commonly transplanted due to its characteristics. Such a procedure is applicable in cases of segmental nerve loss, but it is also used to restore potency in patients after radical prostatectomy. The knowledge of anatomical variants of the sural nerve is also crucial as it allows to minimize its damage during surgical procedures. Furthermore, during an ankle surgery, a nerve block can be used to complement anesthesia. The major aim of this work is to review contributions of the sural nerve to physiological and pathophysiological processes. Full article

Nasal delivery is a non-invasive strategy for effective drug delivery. Nevertheless, in order to promote drug uptake by the nasal mucosa, it is fundamental to increase its residence time in the administration site. To this aim, nano-sized drug delivery systems are widely exploited. Within this context, the commercially available nanoemulsion for parenteral nutrition is a biocompatible, safe and clinically approved vehicle for drug delivery. Furthermore, the nanodroplet surface can be modified via a well-established protocol to graft Concavalin A, a lectin capable of improving the mucosal adhesion, by binding to the α-mannose and α-glucose residues of the mucosal glycocalyx. The obtained targeted formulation is able to induce haemagglutination, as opposite to non-modified nanoemulsion. Furthermore, the ConA grafting maintains the physicochemical properties of the nanodroplets (size~230 nm, Z < −35 mV) and does not interfere with the loading of the Rose Bengal fluorescent probe. Fluorescently labelled ConA grafted nanodroplets showed enhanced permeation and accumulation in ex vivo bovine nasal mucosa. This study is a proof of concept that Concanavalin A can be used to decorate the surface of nanodroplets, acting as a permeation promoter. Full article