Search Results (109)

Localised cutaneous leishmaniasis (LCL) is a common neglected tropical disease in Ethiopia, which is mainly treated with intralesional (IL) pentavalent antimonial such as sodium stibogluconate (SSG) and/or cryotherapy. Both treatments are painful, and studies are lacking on the pain associated with these or affected individuals’ experiences of them. A cross-sectional, observational study was conducted at ALERT Comprehensive Specialized Hospital, Addis Ababa/Ethiopia. The socio-demographic and clinical data of individuals affected by LCL receiving IL SSG and/or cryotherapy was gathered, and their treatment was observed. Participants quantified their treatment-associated pain using the Wong–Baker Pain Scale. Health-related quality of life was measured using the (Children’s) Dermatology Life Quality Index. Adverse effects, participant experiences with local therapies, and dermatologists’ experiences and opinions of local LCL treatment were assessed using structured questionnaires. Of the thirty-six individuals with LCL included (64% male, 14% children), 52% reported a treatment-associated pain score ≥ 8. Cryotherapy administered with a cotton bud was associated with lower pain scores ≤ 6 (odds ratio: 0.15, 95% confidence interval: 0.03–0.89) compared to a cryotherapy spray device. There was wide variation in treatment administration. Local LCL treatment is painful, and most individuals experience significant pain. This study highlights the need for less painful but effective treatments, structured training, and clear standard operating procedures. Full article

Background: Basal cell carcinoma (BCC) is the most common skin cancer worldwide, with a multifactorial aetiology involving environmental and intrinsic factors. A small subset of patients develops high-frequency BCC (HF-BCC), defined as ≥9 BCCs within 3 years. Objective: To analyse demographic, clinical, and histopathological features of non-syndromic HF-BCC in a Belgian cohort, compared with low-burden BCC patients and healthy controls. Methods: A retrospective cohort study was conducted at Erasme Hospital (Brussels) using data from the EUSCAP platform. Clinical, behavioural, and histopathological data were collected and statistically analysed. Results: Of 783 patients, 16 with HF-BCC were identified. For comparison, 32 patients with 1–2 BCCs and 117 patients without BCC were selected. HF-BCC patients showed distinct characteristics, including a higher proportion of superficial BCCs (68.3% vs. 50%, p = 0.01) and fewer nodular subtypes (43.2% vs. 63.5%, p = 0.01). Their tumours were less frequently located on the nose and ears compared with patients having 1–2 BCCs. HF-BCC was associated with a personal history of squamous cell carcinoma (SCC) and actinic keratosis (AK). Conclusions: HF-BCC patients display distinct anatomical, histopathological and clinical characteristics, with a predominance of superficial BCC and an association with a personal history of SCC and AK. They show a lower frequency of tumours on the nose and ears, with a stronger tendency for localisation on the trunk and extremities. Identifying risk factors and genetic markers may contribute to improved early detection strategies, preventive measures, and the development of targeted therapies. Full article

Background/Objectives: In many cases, the detection of a single lesion could revolutionise patient clinical management; not all localisations, especially those with a low uptake and, consequently, a low Tumour-to-Background Ratio (TBR), are readily detectable using [¹⁸F]F-FDG PET/CT. LAFOV-PET offers a potential enhancement in lesion detection, but the proportion of patients who would benefit from its use has yet to be determined. With the present analysis, we aimed to assess which clinical contexts the enhancement in lesion detection could affect the most. Methods: This retrospective study included 764 patients who underwent [¹⁸F]F-FDG PET/CT between January and April 2024. Data were obtained through a review of PET/CT reports. Inclusion criteria comprised patients who attended our centre for cancer pathologies or masses of undetermined nature (MUNs) in a staging setting, excluding patients who had undergone a prior [¹⁸F]F-FDG PET/CT scan or who had received therapy for any cancer pathology. This analysis focused on the total number of lesions identified, as well as the SUVmax of the lesion with the highest uptake. We analysed the proportion of patients who were within the range of number of lesions between 1 and 2, as well as who had an SUVmax of the lesion with the highest uptake between 2 and 5, either in the whole patient population or in the pathologies with a larger numerosity in the present study. Results: Among the 862 scans analysed, 289 (34%) were found to be negative, while 573 (66%) presented at least one localisation. In total, 4.5% of patients presented both a lesion number of between 1 and 2 and an SUVmax of the lesion with the highest uptake between 2 and 5. Among the malignancies that were the most common in the analysed population, a higher-than-average proportion of patients meeting these criteria were found in melanoma (6.2%), breast cancer (5.9%), and multiple myeloma (4.8%) patients. Conversely, the conditions that presented a lower proportion of patients in this range were suffering from MUNs (4.0%), lung cancer (2.1%), head–neck cancer (2.1%), suspected lymphoma (2.0%), and colon cancer (0.0%). Conclusions: Our analysis shows that almost 1 in 20 patients evaluated at oncological staging with [¹⁸F]F-FDG PET/CT could benefit from the increased diagnostic sensitivity offered by LAFOV-PET scanners. These data, although preliminary, support the need for future prospective controlled studies to confirm the actual clinical impact of implementing LAFOV-PET in current practice. Full article

Bacillus Calmette–Guérin (BCG)-related immune reconstitution inflammatory syndrome (IRIS) is a recognised complication following antiretroviral therapy (ART) initiation in HIV-infected infants. We report the case of a 19-month-old child with undiagnosed perinatally acquired HIV due to maternal nondisclosure. The child developed ipsilateral axillary lymphadenitis at the BCG vaccination site shortly after starting ART. The clinical features and temporal association with ART supported a diagnosis of BCG-IRIS. The child was successfully managed with conservative pharmacological treatment alone—rifampicin, isoniazid, and macrolide therapy—without surgical incision or corticosteroids. Progressive improvement of the lesion was observed, and complete clinical resolution occurred over the following months, alongside immune recovery. This case underscores the importance of recognising BCG-IRIS, even in settings where HIV diagnosis may be delayed, and supports the feasibility of conservative management in paediatric patients, potentially avoiding surgical intervention in settings of localised disease. Full article

Background: Endophthalmitis is a rare, sight-threatening condition resulting from infection inside the eye. This study more accurately characterises the cytokines upregulated in human endophthalmitis, and for the first time demonstrates a correlation with cytokine elevation in the serum. Methods: We recruited 39 patients, 17 with endophthalmitis and 22 controls. We compared cytokine expression quantified through cytometric bead assays for both vitreous and serum. Conclusions: The cytokine profile in the vitreous of patients with infectious endophthalmitis was suggestive of a highly inflammatory environment, as 23/26 cytokines examined were significantly elevated. In the patient sera, MMP-9, MPO, Calprotectin, NGAL, SAA (HVIP1), and MCP-1 (HIP1) were all significantly elevated in endophthalmitis samples, which was unexpected as pathology was thought to be localised with minimal systemic effects. Overall, many of the observed cytokines in endophthalmitis are associated with neutrophil responses, and we believe that this deserves further investigation with a view to developing immunomodulatory therapies to prevent endophthalmitis or improve clinical outcomes. Furthermore, our novel demonstration that cytokine elevation associated with endophthalmitis can be demonstrated in serum may allow for novel and rapid interventions. Full article

This retrospective multicentre study investigated haemorrhagic myelopathy as a rare complication of steroid-responsive meningitis-arteritis (SRMA) in nine dogs. The affected dogs exhibited varied neurological deficits, including cervical hyperesthesia, generalised stiffness, ambulatory tetraparesis, and, in the most severe cases, paraplegia without nociception. MRI findings primarily localised haemorrhagic lesions to the thoracolumbar (T3-L3) region, with intradural–extramedullary haemorrhages being the most common type. Most cases responded favourably to immunosuppressive therapy with prednisolone, either alone or in combination with cytarabine. Surgical intervention, performed in a case of compressive extradural haemorrhage, led to a successful recovery of ambulation. Two cases presented or developed paraplegia without nociception, despite immunosuppression. These findings emphasise the importance of advanced imaging and timely therapeutic interventions in addressing atypical and severe manifestations of SRMA. Full article

Common antibiotic therapies to treat bacterial infections are associated with systemic side effects and the development of resistance, directly connected to duration and dosage. Local drug delivery systems (DDSs) offer an alternative by localising antibiotics and thereby limiting their side effects while reducing the dosage necessary. A biodegradable polyester polycaprolactone (PCL)-based DDS was thus produced, containing various clinically relevant drugs. It was shown that the incorporation of four distinct antibiotic classes (amoxicillin, doxycycline, metronidazole and rifampicin), with very high mass fractions ranging up to 20 wt%, was feasible within the PCL matrix. This DDS showed the capacity for effective and sustained release. The release kinetics over 14 days were proven, showing a significant decrease in cytotoxicity with smooth muscle cells as well as an antibacterial effect on (1) aerobic, (2) anaerobic, (3) Gram-positive and (4) Gram-negative pathogens in vitro. The DDS demonstrated a markedly diminished cytotoxic impact owing to sustained release in comparison to pure antibiotics, while simultaneously maintaining their antibacterial efficacy. In conclusion, DDSs are a more tolerable form of antibiotics administration due to the hydrophobic PCL matrix causing a slower diffusion-controlled release, proven as a release mechanism via the Peppa–Sahlin model. Full article

Background: Metritis, a common postpartum uterine infection in bovines, poses substantial challenges in livestock management, including compromised fertility and economic losses. Poor uterine drug penetration and systemic side effects, necessitating innovative localised delivery systems and limiting current systemic antibiotic treatments. Aim: This study aimed to develop and evaluate the potential effect of the ofloxacin-loaded hydrogel as a localised drug delivery system to treat metritis in bovine. The focus was on achieving sustained drug release, enhanced antibacterial efficacy and reduced inflammation in the endometrium. Materials and Methods: The CS/PVA hydrogel was synthesised using a freeze–thaw method and further optimised for drug encapsulation efficiency (96.7 ± 2.1%), stability and biocompatibility. Physicochemical characterisation included swelling behaviour, mechanical properties and rheological analysis. In vitro drug release profiles in the simulated uterine fluid were assessed over 72 h and antibacterial activity was tested against common uterine pathogens such as Escherichia coli and S. aureus. In vivo studies were conducted on bovines diagnosed with endometritis to evaluate clinical recovery. Results: The SEM image of the ofloxacin-loaded CS/PVA hydrogel resulted in a smooth and porous structure demonstrating larger pore size than the blank. The rheological study suggested higher stability and elastic behaviour. Antibacterial assays on E. coli and S. aureus revealed significant inhibition zones, respectively, indicating potent efficacy. In vivo, evaluated on treated bovine, reduced bacterial loads were exhibited (2.86 × 10^5A CFU/mL → 6.37 × 10^2B CFU/mL), clinical improvement was marked and uterine inflammation was resolved. Conclusions: Ofloxacin-loaded hydrogels represent a promising localised treatment for bovine metritis, offering sustained antibacterial action and improved clinical outcomes. This approach addresses the limitations of systemic antibiotic therapies and provides a practical solution for enhanced veterinary care. Further studies are recommended to validate these findings in more extensive field trials and explore commercialisation potential. Full article

Phosphodiesterase 4 (PDE4) is a key regulator of cyclic adenosine monophosphate (cAMP) signalling in cardiomyocytes, controlling contractility, calcium handling, and hypertrophic responses. PDE4 provides spatial and temporal precision to cAMP signalling, particularly under β-adrenergic stimulation, through its compartmentalised activity in subcellular nanodomains, including the sarcoplasmic reticulum, plasma membrane and nuclear envelope. This review highlights the cardiac PDE4 isoforms PDE4A, PDE4B and PDE4D, focusing on their distinct localisation and contributions to cardiac physiology and pathophysiology, particularly in heart failure and arrhythmias. Although PDE4 plays a smaller role in overall cAMP hydrolysis in human hearts than in rodents, its compartmentalised function remains critical. Recent therapeutic advances have shifted from pan-PDE4 inhibitors to isoform-specific approaches to enhance efficacy while minimising systemic toxicity. We discuss the potential of selective PDE4 modulators, gene therapies and combination strategies in restoring cAMP compartmentation and preventing maladaptive cardiac remodelling. By integrating rodent and human studies, this review underscores the translational challenges and therapeutic opportunities surrounding PDE4, positioning it as both a key regulator of cardiac signalling and a promising target for heart failure therapies. Full article

Pseudomonas aeruginosa is one of the leading causes of nosocomial respiratory tract infections, significantly affecting morbidity and mortality. It can persist in the lungs of patients with cystic fibrosis (CF) for extended periods because of its adaptive capacity. The main aim of this study was to determine the phenotypic and genotypic resistance to antibiotics of clinical isolates of P. aeruginosa that persist in patients with CF receiving long-term antimicrobial therapy. The study included nine strains of P. aeruginosa isolated from the sputum of patients with CF admitted to the hospital. Susceptibility to antibiotics was determined using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria. Whole-genome sequencing was performed for phylogeny, sequence typing, and to identify antibiotic-resistant genes. The study showed that during long-term persistence in the lungs of patients receiving antibacterial therapy, the restoration of susceptibility to antibiotics occurred in some cases. Multilocus sequence typing and phylogeny revealed six sequence types. Functional annotation identified 72 genes responsible for resistance to antibacterial and chemical substances, with either chromosomal or plasmid localisation. Full article

Boron Neutron Capture Therapy (BNCT) is a therapeutic approach used to treat malignancies that are difficult to localise and typically inoperable. This therapy involves two stages: the administration of the boron (¹⁰B) isotope, which selectively enters cancer cells without affecting healthy tissue, followed by irradiation of the tumour with a neutron beam. In this study, boron carbide (B₄C), a ceramic material with exceptional physical and chemical properties, was used as a nanoparticle platform for BNCT. The surface of the boron carbide nanoparticles was optimised by modifying them with compounds such as dextrin, dextran T70, sorbitol, lysine, and arginine. Boron carbide was synthesised directly from boron and carbon and then subjected to grinding, washing, and centrifugation. The unmodified and modified samples were analysed for their particle size, zeta potential, and toxicity against glioblastoma T98G cells. Additionally, FTIR spectroscopy confirmed the successful surface modifications. The results demonstrate that boron carbide, as a ceramic material, can be effectively functionalised with biocompatible compounds. Among the tested modifications, B₄C-dextrin and B₄C-dextran T70 exhibited the highest toxicity towards cancer cells, demonstrating the potential of ceramic platforms in biomedical applications. Full article

Background: stereotactic ablative body radiotherapy (SABR) is a disruptive radiation therapy technique which is increasingly used for the treatment of urologic cancers. The aim of this narrative review is to provide an overview on the current landscape of SABR in urologic cancers and highlight advancements on the horizon. Methods: a narrative review of the contemporary role of SABR in urologic cancers is conducted. Results: in localised prostate cancer, SABR boasts excellent tumour control and biochemical control, with acceptable GU and GI toxicity. Its comparison to laparoscopic radical prostatectomy is currently ongoing. SABR appears to be practical for metastasis-directed therapy in metastatic prostate cancer, with good local control and a low toxicity profile, either alone or in combination with ADT. In localised RCC, SABR offers adequate local control with a modest impact on renal function in patients unfit for surgical management. Its role in metastatic RCC is much more established, where it has been shown to be superior to conventional radiotherapy. Emerging evidence suggests that SABR has a role in delaying systemic therapy whilst maintaining QOL and overall survival. Intriguingly, in metastatic prostate cancer and metastatic RCC, SABR results in a cytoreductive and immunomodulatory ‘abscopal effect’, a focus of current investigations. Conclusions: SABR has emerged as a safe, effective, and feasible treatment for urologic cancers. Urologists should be aware of its increasing use in localised prostate cancer and metastatic RCC, with good oncological outcomes combined with acceptable toxicity. In addition, SABR holds promise for both metastatic prostate cancer and localised RCC treatment in terms of toxicity and oncological outcomes. Full article

Myocardial ischaemia reperfusion injury (IRI) occurring from acute coronary artery disease or cardiac surgical interventions such as bypass surgery can result in myocardial dysfunction, presenting as, myocardial “stunning”, arrhythmias, infarction, and adverse cardiac remodelling, and may lead to both a systemic and a localised inflammatory response. This localised cardiac inflammatory response is regulated through the nucleotide-binding oligomerisation domain (NACHT), leucine-rich repeat (LRR)-containing protein family pyrin domain (PYD)-3 (NLRP3) inflammasome, a multimeric structure whose components are present within both cardiomyocytes and in cardiac fibroblasts. The NLRP3 inflammasome is activated via numerous danger signals produced by IRI and is central to the resultant innate immune response. Inhibition of this inherent inflammatory response has been shown to protect the myocardium and stop the occurrence of the systemic inflammatory response syndrome following the re-establishment of cardiac circulation. Therapies to prevent NLRP3 inflammasome formation in the clinic are currently lacking, and therefore, new pharmacotherapies are required. This review will highlight the role of the NLRP3 inflammasome within the myocardium during IRI and will examine the therapeutic value of inflammasome inhibition with particular attention to carbon monoxide, nitric oxide, and hydrogen sulphide as potential pharmacological inhibitors of NLRP3 inflammasome activation. Full article

The AurkA serine/threonine kinase is a key regulator of cell division controlling mitotic entry, centrosome maturation, and chromosome segregation. The microtubule-associated protein TPX2 controls spindle assembly and is the main AurkA regulator, contributing to AurkA activation, localisation, and stabilisation. Since their identification, AurkA and TPX2 have been described as being overexpressed in cancer, with a significant correlation with highly proliferative and aneuploid tumours. Despite the frequent occurrence of AurkA/TPX2 co-overexpression in cancer, the investigation of their involvement in tumorigenesis and cancer therapy resistance mostly arises from studies focusing only on one at the time. Here, we review the existing literature and discuss the mitotic phenotypes described under conditions of AurkA, TPX2, or AurkA/TPX2 overexpression, to build a picture that may help clarify their oncogenic potential through the induction of chromosome instability. We highlight the relevance of the AurkA/TPX2 complex as an oncogenic unit, based on which we discuss recent strategies under development that aim at disrupting the complex as a promising therapeutic perspective. Full article

Cataracts are the world’s leading cause of blindness, and diabetes is the second leading risk factor for cataracts after old age. Despite this, no preventative treatment exists for cataracts. The altered metabolism of excess glucose during hyperglycaemia is known to be the underlying cause of diabetic cataractogenesis, resulting in localised disruptions to fibre cell morphology and cell swelling in the outer cortex of the lens. In rat models of diabetic cataracts, this damage has been shown to result from osmotic stress and oxidative stress due to the accumulation of intracellular sorbitol, the depletion of NADPH which is used to regenerate glutathione, and the generation of fructose metabolites via the polyol pathway. However, differences in lens physiology and the metabolism of glucose in the lenses of different species have prevented the translation of successful treatments in animal models into effective treatments in humans. Here, we review the stresses that arise from hyperglycaemic glucose metabolism and link these to the regionally distinct metabolic and physiological adaptations in the lens that are vulnerable to these stressors, highlighting the evidence that chronic oxidative stress together with osmotic stress underlies the aetiology of human diabetic cortical cataracts. With this information, we also highlight fundamental gaps in the knowledge that could help to inform new avenues of research if effective anti-diabetic cataract therapies are to be developed in the future. Full article