Diagnostic Tests for Female Bladder Outlet Obstruction : A Systematic Review from the European Association of Urology Non-neurogenic Female LUTS Guidelines Panel

Acknowledgements Jae Hung Jung, Murat Gul, Ege Can Serefoglu (translation of foreign language articles) and Karin Plass for administrative support.Peer reviewedPostprin

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

DEVELOPING A TISSUE ENGINEERED AUTOLOGOUS FASCIAL GRAFT FOR PELVIC FLOOR RECONSTRUCTIVE SURGERY

Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are common problems that affect many women. Approximately 1 in 10 women will require surgery to treat one or both conditions during their lifetime. Recently, surgical repair has utilized non-degradable synthetic mesh which has led to an incidence of serious complications such as exposure in up to 15% of patients. The main aim of this thesis was to produce a pelvic floor repair material (PFRM), composed of an electrospun synthetic polymeric scaffold seeded with autologous fibroblasts, that is robust enough for surgical handling and has adequate mechanical properties to enforce/or reinforce repair techniques used for SUI and POP at the point of implantation and beyond. We produced and evaluated 5 polymeric scaffolds and identified that 2, random fibre electrospun scaffolds composed of PLA and PU, most closely resembled native vaginal tissue in mechanical properties whilst having the best handling characteristics. The response of fibroblasts on scaffolds to mechanical conditioning was then evaluated using three simple models. Dynamic uniaxial tension (stretch) using near physiological strains led to organization of the extracellular matrix and was the most promising conditioning technique. Future work will further assess responses of scaffolds and cell/scaffold combinations to repetitive stretch. The response of fibroblasts on scaffolds to a variety of bioactive factors added to the culture media was also assessed. Dexamethasone and Ascorbic acid supplementation led to significant increases in the production of ECM proteins and mechanical properties of cell-seeded polymeric scaffolds. In future, it may be useful to integrate these factors into polymeric scaffolds so that they are released into the wound bed with the aim of providing an ongoing stimulus for ECM production and the maintenance of the mechanical integrity of healing tissues

Underactive bladder: Pathophysiology and clinical significance

Underactive bladder (UAB) is a voiding disorder which generates disabling lower urinary tract symptoms (LUTS) due to the inability to produce an effective voiding contraction sufficient to empty the bladder. The underlying abnormality, that is usually appreciated when performing urodynamic studies, has been defined by the International Continence Society (ICS) as detrusor underactivity (DUA). DUA is a common yet under-researched bladder dysfunction. The prevalence of DUA in different patient groups suggests that multiple aetiologies are implicated. Currently there is no effective therapeutic approach to treat this condition. An improved understanding of the underlying mechanisms is needed to facilitate the development of new advances in treatment. The purpose of this review is to discuss the epidemiology, pathophysiology, common causes and risk factors potentially leading to DUA; to aid in the appropriate diagnosis of DUA to potentially improve treatment outcomes

Assessment of BPH/BOO

The assessment of men with bladder outflow obstruction relies on an adequate history and examination. Uroflowmetry and post-void residue estimation are very revealing and may be sufficient in the majority of men. The prostate-specific antigen test may be used to select men who are at a high risk of progression. In specific situations, cystometry may be required. We discuss the use of cystometry and the newer less-invasive methods of assessment that have emerged over the last few years, including ultrasound estimation of intravesical prostatic protrusion, prostatic urethra angle, detrusor wall thickness, ultrasound-estimated bladder weight, near-infrared spectroscopy and the condom catheter and penile cuff tests. Although these techniques show promise, they still require further modifications, standardization and testing in larger populations. In addition, they should be used in men where only specific questions need to be answered

Health And Wellbeing Impact And Treatment of Nocturia – A Review of The Literature

Nocturia is a prevalent and highly bothersome lower urinary tract symptom (LUTS) affecting men and women of all ages. In waking to void there is disruption to an individual’s sleep that can lead to daytime tiredness and a loss of vitality. This may significantly impact upon physical, mental, and social wellbeing. It is recognised that nocturia has a multifactorial aetiopathogenesis that encompasses systemic, psychogenic, as well as lower urinary tract factors, necessitating separate evaluation to other LUTS. In particular, nocturnal polyuria is an under-recognised cause of nocturia that may respond well to antidiuretic pharmacotherapy

Non‑Hormonal treatment of BPH/BOO

Objectives: To review the use of non-hormonal pharmacotherapies in the treatment of lower urinary tract symptoms (LUTS) due to presumed benign prostatic hyperplasia (BPH). Materials and Methods: A search of the PUBMED database was conducted for the terms BPH, LUTS, bladder outlet obstruction, alpha-adrenoceptor blockers, anti-muscarinics, and phosphodiesterase-5-inhibitors. Results: Medical therapy has long been established as the accepted standard of care in the treatment of male LUTS. The aim of treatment is improvement in symptoms and quality of life whilst minimizing adverse effects. The agents most widely used as 1 st line therapy are alpha-blockers (AB), as a standalone or in combination with 2 other classes of drug; 5-α reductase inhibitors and anti-muscarinics. AB have rapid efficacy, improving symptoms and flow rate in a matter of days, these effects are then maintained over time. AB do not impact on prostate size and do not prevent acute urinary retention or the need for surgery. Anti-mucarinics, alone or in combination with an AB are safe and efficacious in the treatment of bothersome storage symptoms associated with LUTS/BPH. Phosphodiesterase-5 inhibitors are an emerging treatment option that improve LUTS without improving flow rates. Conclusions: AB are the most well-established pharmacotherapy in the management of men with LUTS/BPH. The emergence of different classes of agent offers the opportunity to target underlying pathophysiologies driving symptoms and better individualize treatment