Anthony Kupelian

Discrediting microscopic pyuria and leucocyte esterase as diagnostic surrogates for infection in patients with lower urinary tract symptoms: Results from a clinical and laboratory evaluation

Microscopic pyuria is widely used as a surrogate marker of infection, although there is little data supporting its use in patients who present with non‐acute LUTS. The effects of urinary storage, preservation, and the use of laboratory methods to enhance leucocyte detection, are also unclear. This large, prospective study highlights the poor performance of dipstick urine analysis, and direct microscopy, as surrogate markers of UTI in patients with LUTS. A series of laboratory analyses also examine the effects of urine handling and processing on test integrity, which have important implications for clinical practice.

Enterococcus faecalis subverts and invades the host urothelium in patients with chronic urinary tract infection.

Bacterial urinary tract infections (UTI) are a major growing concern worldwide. Uropathogenic Escherichia coli has been shown to invade the urothelium during acute UTI in mice and humans, forming intracellular reservoirs that can evade antibiotics and the immune response, allowing recurrence at a later date. Other bacterial species, such as Staphylococcus saprophyticus, Klebsiella pneumonia and Salmonella enterica have also been shown to be invasive in acute UTI. However, the role of intracellular infection in chronic UTI causing more subtle lower urinary tract symptoms (LUTS), a particular problem in the elderly population, is poorly understood. Moreover, the species of bacteria involved remains largely unknown. A previous study of a large cohort of non-acute LUTS patients found that Enterococcus faecalis was frequently found in urine specimens. E. faecalis accounts for a significant proportion of chronic bladder infections worldwide, although the invasive lifestyle of this uropathogen has yet to be reported. Here, we wanted to explore this question in more detail. We harvested urothelial cells shed in response to inflammation and, using advanced imaging techniques, inspected them for signs of bacterial pathology and invasion. We found strong evidence of intracellular E. faecalis harboured within urothelial cells shed from the bladder of LUTS patients. Furthermore, using a culture model system, these patient-isolated strains of E. faecalis were able to invade a transitional carcinoma cell line. In contrast, we found no evidence of cellular invasion by E. coli in the patient cells or the culture model system. Our data show that E. faecalis is highly competent to invade in this context; therefore, these results have implications for both the diagnosis and treatment of chronic LUTS.

Urinary ATP as an indicator of infection and inflammation of the urinary tract in patients with lower urinary tract symptoms.

BackgroundAdenosine-5′-triphosphate (ATP) is a neurotransmitter and inflammatory cytokine implicated in the pathophysiology of lower urinary tract disease. ATP additionally reflects microbial biomass thus has potential as a surrogate marker of urinary tract infection (UTI). The optimum clinical sampling method for ATP urinalysis has not been established. We tested the potential of urinary ATP in the assessment of lower urinary tract symptoms, infection and inflammation, and validated sampling methods for clinical practice.MethodsA prospective, blinded, cross-sectional observational study of adult patients presenting with lower urinary tract symptoms (LUTS) and asymptomatic controls, was conducted between October 2009 and October 2012. Urinary ATP was assayed by a luciferin-luciferase method, pyuria counted by microscopy of fresh unspun urine and symptoms assessed using validated questionnaires. The sample collection, storage and processing methods were also validated.Results75 controls and 340 patients with LUTS were grouped as without pyuria (n = 100), pyuria 1-9 wbc μl-1 (n = 120) and pyuria ≥10 wbc μl-1 (n = 120). Urinary ATP was higher in association with female gender, voiding symptoms, pyuria greater than 10 wbc μl-1 and negative MSU culture. ROC curve analysis showed no evidence of diagnostic test potential. The urinary ATP signal decayed with storage at 23°C but was prevented by immediate freezing at ≤ -20°C, without boric acid preservative and without the need to centrifuge urine prior to freezing.ConclusionsUrinary ATP may have a role as a research tool but is unconvincing as a surrogate, clinical diagnostic marker.

Segmental bowel resection for deep infiltrating endometriosis.

Riiskjær et al. report the functional outcome of segmental bowel resection for rectosigmoid endometriosis during the laparoscopic treatment of deep infiltrating disease. This large, prospective study, employing validated outcome measures, is a welcome addition to the literature. We note that some patients who underwent discoid resection of bowel endometriosis were included. Segmental resection and disc resection entail different degrees of dissection, perhaps resulting in variable neurological effects. Injury to the inferior hypogastric plexi and their visceral branches is thought to mediate the functional problems associated with excisional surgery for endometriosis. It remains difficult to determine the impact of bowel resection alone on autonomic function, as the removal of other disease will influence outcome. The authors describe attempts to preserve autonomic nerves during surgery and ‘nerve sparing’ techniques have been reported (Landi et al. Hum Reprod. 2006;21:774–81). Sexual function improved after surgery, driven primarily by a reduction in dyspareunia. Statistically significant improvements in sexual satisfaction, intimacy, desire, and coital frequency were also noted. The reduction in dyspareunia and associated distress represents a change in SVQ responses from ‘quite a bit’ to ‘a little’ and these improvements are likely to be clinically meaningful. At baseline and 1 year postoperatively, almost half of the study population described major symptoms stratified by the LARS questionnaire. Defaecation frequency increased after surgery, although the median scores for other bowel symptoms were unchanged. These data imply that segmental bowel resection should not be undertaken in the expectation that functional bowel symptoms will improve. The impact of surgery on painful defaecation was not reported, although we note plans for future publication. Median ICIQ-FLUTS scores were similar before and after surgery, although the authors did report a reduction in postoperative bladder pain. The pathophysiological explanation for this is unclear. If the effect is real, it could be related to the surgical treatment of bladder lesions or to a reduction in central sensitisation following surgical treatment of disease elsewhere. Measures of central tendency such as the median describe the average characteristics of a population. Although they are informative summary statistics, they can conceal information about the risk of new-onset symptoms. The inclusion of these data might have complemented the analysis. The need for intermittent catheterisation after this type of surgery is common, although voiding usually returns in the longterm (Minelli et al. Arch Surg 2009;144:234–9). Catheter dependence was not reported but would have been an interesting addition. In summary, this large, prospective series demonstrates that in their hands, sexual function after surgery improves, and the median effect of surgery on bladder function is likely neutral. Although bowel frequency increased, patients were no more likely to experience faecal urgency or anal incontinence after surgery than before. Although local excision of bowel endometriosis is preferred to segmental resection where feasible (Fanfani et al. Fertil Steril 2010;94:444–9), these data provide further evidence that segmental resection can be undertaken with a low risk of functional consequences. However, it must be appreciated that the extent of dissection outside the proximity of the bowel is likely to have influenced the results.