Pain related to percutaneous nephrolithotomy (PCNL) is multifactorial and poorly elucidated. However, understanding the pathophysiology of pain can enable a practical approach to pain management, which can be tailored to...Pain related to percutaneous nephrolithotomy (PCNL) is multifactorial and poorly elucidated. However, understanding the pathophysiology of pain can enable a practical approach to pain management, which can be tailored to each patient. A number of potential mechanisms underlie pain perception in PCNL, and these mechanisms can be leveraged at various points on the perioperative care pathway. These interventions provide opportunities for modulation of pain associated with PCNL but must take into account various technical, pharmacological and patient-related considerations. Technical considerations include the influence of percutaneous access, stone removal and drainage techniques. Pharmacological aspects include the use of various analgesics and anaesthesia approaches. Patient factors include consideration of the biopsychosocial model in pain experience to understand each individual's response to pain. By understanding the contemporary evidence surrounding the physiology of postoperative pain and identifying tangible intervention points, we can seek to mitigate postoperative pain in patients undergoing PCNL.
Spatial transcriptomics has emerged as a powerful tool for discerning the heterogeneity of the tumour microenvironment across various cancers, including renal cell carcinoma (RCC). Spatial transcriptomics-based studies c...Spatial transcriptomics has emerged as a powerful tool for discerning the heterogeneity of the tumour microenvironment across various cancers, including renal cell carcinoma (RCC). Spatial transcriptomics-based studies conducted in clear-cell RCC (the only RCC subtype studied using this technique to date) have given insights into spatial interactions within this disease. These insights include the role of epithelial-to-mesenchymal transitioning, revealing proximity-dependent interactions between tumour cells, fibroblasts, interleukin-2-expressing macrophages and hyalinized regions. Investigations into metabolic programmes have shown high transcriptional heterogeneity within tumours, with a tendency of increased metabolic activity towards the tumour centre. T cell infiltration has been shown to be independent of neoantigen burden, although T cell activity correlates with both metabolic states and various transcripts expressed by tumour cells, fibroblasts and monocytes. The role of tertiary lymphoid structures in both plasma cell maturation and their infiltration of the tumour has been shown through tracks of fibroblasts. Collectively, these findings indicate the potential of spatial transcriptomics to reveal predictive spatial features, supporting its promise in the development of biomarkers for clear-cell RCC management.
Multiple conditions can cause hypoxia in the testis, including exposure to high altitude, sleep apnoea, testicular torsion and varicocele. Varicocele accounts for up to 44% of instances of primary infertility, but the cu...Multiple conditions can cause hypoxia in the testis, including exposure to high altitude, sleep apnoea, testicular torsion and varicocele. Varicocele accounts for up to 44% of instances of primary infertility, but the cumulative contribution of hypoxic conditions to male infertility is undefined. Results of controlled hypobaric hypoxia studies have demonstrated a substantial detrimental effect of short-term and long-term exposures on sperm; however, downstream effects on embryo development and offspring health are less well understood. Hypoxia can have direct and indirect effects on the molecular biology and biochemistry of germ cells, including changes to gene expression, metabolism, oxidative stress and to the endocrine environment. Hypoxia also has often-overlooked effects on the epididymis, such as altered composition and gene expression of epithelial cells, with knock-on effects on sperm maturation, including the capacity to acrosome react. Evidence from model species shows that paternal hypoxia exposure results in disrupted embryo development and transgenerational effects on male fertility and offspring physiology. Overall, hypoxia induces a complex, multifaceted subfertility phenotype that is reversible with resolution of the exposure, in part because of a resilient testis stem cell population that thrives in hypoxia. However, the potential for transgenerational effects deserves further exploration, particularly in considering the purported decline in sperm counts over the past 50 years.
A number of reports have suggested that the use of prolonged antibiotic treatment could be an effective therapy for patients with overactive bladder (OAB); however, this approach is contrary to existing recommendations r...A number of reports have suggested that the use of prolonged antibiotic treatment could be an effective therapy for patients with overactive bladder (OAB); however, this approach is contrary to existing recommendations regarding the prolonged non-specific use of antibiotics. The existing evidence in this area seems to be circumstantial and anecdotal but, despite this limitation, the use of long-term antibiotic therapy for OAB seems to be increasing. Review and synthesis of the existing evidence for use of antibiotic therapy in patients with OAB identify few studies - just seven papers and four conference proceedings - which are heterogeneous in their design, inclusion and exclusion criteria, treatment regimen employed, approach to the use of antimuscarinic medications, follow-up protocols, and measured outcomes. Overall, the limitation of these published data, the potential adverse events associated with long-term antibiotic use, concerns about antimicrobial resistance and the wide availability of other conventional treatments mean that no compelling data support the routine use of antibiotic therapy and that antibiotic treatment of OAB is not supported by an adequate contemporary evidence base. In the absence of acute urinary tract infection, the management of the non-specific syndrome of OAB should follow existing evidence-based investigational and treatment guidelines. Contemporary therapy following attention to fluid intake relies upon anticholinergic or β3-adrenergic agonist treatment with progression to intravesical onabotulinumtoxinA therapy or neuromodulation in non-responders to oral therapy.
Neuromodulation has been used in the treatment of various pelvic organ dysfunctions for almost 40 years and several placebo-controlled studies have confirmed its clinical effect. Many neuromodulation methods using differ...Neuromodulation has been used in the treatment of various pelvic organ dysfunctions for almost 40 years and several placebo-controlled studies have confirmed its clinical effect. Many neuromodulation methods using different devices and stimulation parameters, targeting different neural structures have been introduced, but only a limited number have been adopted into routine clinical use. A substantial volume of basic research and clinical studies addressing specific effects of neuromodulation in the treatment of overactive bladder (OAB) have been published to date; however, their mechanistic implications have not been comprehensively summarized. Thus, our understanding of the mechanism of action of neuromodulation in OAB treatment is mainly based on postulated theories. Results from animal experiments suggest that different neuromodulation methods used to treat OAB share the same basic principles. The most likely explanation for the effect of neuromodulation in OAB therapy is the suppression of bladder afferent signalling, promotion of spinal guarding reflexes and modulation of non-specific supraspinal regulatory circuits.