Tag Archive for: Translational Science


Article of the Week: Indoor cold exposure and nocturia

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Indoor cold exposure and nocturia: a cross-sectional analysis of the HEIJO-KYO study

Keigo Saeki, Kenji Obayashi and Norio Kurumatani
Department of Community Health and Epidemiology, Nara Medical University School of Medicine, Nara, Japan



To investigate the association between indoor cold exposure and the prevalence of nocturia in an elderly population.

Subjects and Methods

The temperature in the living rooms and bedrooms of 1 065 home-dwelling elderly volunteers (aged ≥60 years) was measured for 48 h. Nocturia (≥2 voids per night) and nocturnal urine production were determined using a urination diary and nocturnal urine collection, respectively.



The mean ± sd age of participants was 71.9 ± 7.1 years, and the prevalence of nocturia was 30.8%. A 1 °C decrease in daytime indoor temperature was associated with a higher odds ratio (OR) for nocturia (1.075, 95% confidence interval [CI] 1.026–1.126; P = 0.002), independently of outdoor temperature and other potential confounders such as basic characteristics (age, gender, body mass index, alcohol intake, smoking), comorbidities (diabetes, renal dysfunction), medications (calcium channel blocker, diuretics, sleeping pills), socio-economic status (education, household income), night-time dipping of ambulatory blood pressure, daytime physical activity, objectively measured sleep efficiency, and urinary 6-sulphatoxymelatonin excretion. The association remained significant after adjustment for nocturnal urine production rate (OR 1.095 [95% CI 1.042–1.150]; P < 0.001).


Indoor cold exposure during the daytime was independently associated with nocturia among elderly participants. The explanation for this association may be cold-induced detrusor overactivity. The prevalence of nocturia could be reduced by modification of the indoor thermal environment.

Editorial: Does cold exposure cause nocturia?

We have all experienced that changing from a warm environment to a colder external temperature may provoke a sudden compelling desire to void. This feeling fits quite well with part of the definition of urgency following the International Continence Society definition. Consequently, it is logical to suspect that cold exposure during daytime may influence bladder behaviour and hence contribute to nocturia episodes. These Japanese authors [1] performed a cross-sectional analysis as part of a community based cohort study in 1127 home-dwelling volunteers aged ≤60 years. Living room and bedroom temperatures were measured for 48 h and the participants completed voiding charts and nocturnal urine collection, but were excluded if >12 h were spent outside their house. The mean age of the participants was ≈72 years and nocturia was present in 30.8%. A decrease in daytime indoor temperature of 1 °C was associated with a higher odds ratio for nocturia and this was independent of outdoor temperature and other potential confounders. Furthermore, the association was independent of nocturnal urine production and hence reflect a direct effect on bladder behaviour, probably due to detrusor overactivity. However, a change of indoor temperature modified nocturia in only 29.3% of participants, and varied significantly in individuals. Nevertheless, these findings could be used as a population approach to reduce the prevalence of nocturia and hence the eventual impact on quality of life and morbidity that is known to go together with nocturia.

Philip Van Kerrebroeck, Professor of Urology
Department of Urology, Maastricht University Medical Centre, Maastricht, The Netherlands


1 Saeki K, Obayashi K, Kurumatani N. Indoor cold exposure and nocturia: a cross-sectional analysis of the HEIJO-KYO study. BJU Int 2016; 117: 82935



Importance of fundamental science as the cornerstone for translational research

fwefwefResearch headlines that attract the most publicity are those that show success in benetting patients, whether it is through new targeted drugs or new immunotherapies. Many funding bodies and charities have also changed their policy toward funding more translational research that has clear economic, clinical and patient benet. We must remember, however, that the innovations for these transformative publications and translational research projects are imbedded in our fundamental understanding of the molecular and cellular biology of disease investigated at the basic science level. These investigations are the cornerstone of translational research.


The BJUI has continued its tradition of publishing fundamental research with translational insight, and this is exemplied in this months article by Liu et al. [1], which undertakes to explain the mechanistic and functional role of EZH2 in RCC. In this study the authors manipulate the expression of EZH2 by silencing it using short-hairpin EZH2, which targets the RNA. They also use a small molecule inhibitor of methyltransferase which has been shown to deplete the expression of EZH2. Both these approaches inhibit EZH2 expression, which was associated with reduced migration and invasion of the cancer cells, as assessed in in vitro models, as well as with slowintumour growth and prolonging survival in an in vivo nude mouse model. These changes were mechanistically explained by a change in the mesenchymal epithelial transition phenotype of the tumour cells. The authors then went on to show that EZH2 is associated with E-cadherin suppression and poor survival in patients with RCC, demonstrating the translational importance of these ndings.


This impo rtant fundamental and translational paper adds to the growing body of evidence that EZH2, which is a histone methyltransferase and regulator of gene expression, plays key role in the development of a range of cancers including prostate, breast, lymphoma and colon [2]


The Translational Science section of the BJUI is looking for relevant and citable articles similar to the paper by Liu et al., which are imbedded in fundamental science and bring the concept into clinical investigation, either through its validation in clinical material or manipulation in clinically relevant in vivo model systems, and represent a clear translational step.


To facilitate our readers understanding and to familiarizthem with often complicated and complex fundamental scientic concepts, in 2013 the BJUI introduced the Science Made Simple review-type article section, in which various scientic concepts are explained so as to assist interactions between scientists and clinicians as they translate their ideas and ndings into clinical utility.





2 Simon JA, Lange CA. Roles of the EZH2 histone methyltransferase in cancer epigenetics. Mutat Res 2008; 647: 219


R. William Watson, BJUI Consulting Editor, Translational Science


UCD School of Medicine and Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland


Clever surgeons and challenging study endpoints

CaptureIntraoperative in vivo tracking of a periprostatic nerve with multiphoton microscopy in rat model.

In the last 6 months, the BJUI editorial team has evaluated an average of 59 urological oncology papers per month with an average acceptance rate of 16%. We receive additional papers for our ‘Translational Science’ section. Studies with high-quality methods are given the highest priority. Other papers compete well if they are highly applicable to clinical practice (i.e. comparative, multicentre, multi-surgeon design) and/or show us new ideas in surgical technique, re-designed study endpoints, or explore new sources of data. For translational science, the best candidates are studies that look at new diagnostic tests in humans and beyond simple immunostaining techniques. We want to evaluate biomarkers likely to be validated and translated into a clinical test. Clinical impact will be even higher if a biomarker is linked to a therapy outcome rather than just a risk estimate. We want our papers to guide us to better outcomes for our patients, hopefully control healthcare costs, and, yes, be well-cited in the literature.

Our review process is tough but fair, and we congratulate and highlight three authorship groups for acceptance into this month’s issue of BJUI. The theme of ‘clever surgeons and challenging study endpoints’ is well illustrated by all three groups. Zargar et al. [1] report on an exclusive database of high-volume minimally invasive surgeons who have tackled the partial nephrectomy option for small renal masses. The comparison is simple in concept and retrospective in design, but what they have done is to significantly increase the outcome measures into a ‘trifecta’ concept in perioperative outcomes (previously reported) with an even more stringent ‘optimal outcome’ endpoint that includes renal function preservation. With a database of 1185 robotic and 646 laparoscopic cases, the robotic procedures showed superior trifecta results (70% vs 33%), complication rates (14.8% vs 20.9%), positive surgical margin rates (3.2% vs 9.7%), and warm ischaemia time (18 vs 26 min). The optimal outcome endpoint included a minimum 90% estimated GFR (eGFR) preservation and no chronic kidney disease upstaging. Only the robotic cohort had sufficient data available and the rate was 38.5%. The latter figure is an interesting challenge, as defining such a high threshold for success challenges surgical technique and allows more room to identify incremental advancement. This may be the largest study of its kind, but non-randomised and with limitations discussed in peer review such as the learning curve influence, use of eGFR as an endpoint with two kidneys, and incomplete data. The definitions used are of interest and the field could use some uniformity moving forward in measuring perioperative and long-term benchmarks of quality.

Durand et al. [2] give us a glimpse into the future of surgery, a science fiction world of prostate surgery where nerves and prostatic glands can be colour coded and seen at a microscopic level in real time. The pictures stand for themselves, especially Fig. 1. If such imaging can be integrated into technique decisions, and perhaps future instrument designs, then perhaps we will have a whole new wave of studies possible on linking surgical technique to improved functional and oncological outcomes after radical prostatectomy. The paper has a nice depth in detail, methods, results, as well as narratives in solving technical problems with novel technology.

This issue’s ‘Article of the Month’ by Gavin et al. [3] is a different look at the question of morbidity after localised prostate cancer treatments, specific to long-term care at >2 years from treatment. The database is from a cancer registry and they have an impressive 54% response rate from a population that is 2–18 years from diagnosis. Rather than Likert-like scales of symptom severity, they simply look at ‘current’ vs ‘ever had’ symptoms and look at the total burden including multiple/overlapping symptoms. Although this may not be as robust and validated as the Expanded Prostate Cancer Index Composite (EPIC) instrument, the simple phrasing of ‘current’ vs ‘ever had’ is probably capturing a very high proportion of symptoms rather than dismissing them if minor or in the past. Again, we see more erectile dysfunction after radical prostatectomy and radiation with hormonal therapy, and more bowel symptoms after radiation therapy. Hormone therapy patients have hot flashes and fatigue, and watchful-waiting patients have some advantages but are certainly not free of symptoms. The burden of symptoms is interesting, nine of 10 reported at least one of seven key symptoms at some point and three of four are current. Therefore, as the authors indicate, ≈75% of prostate cancer survivors will have ongoing symptoms needing follow-up care. This is a significant database resource adding to our understanding of long-term outcomes of patients with prostate cancer and supporting the significance of the Durand et al. [2] study that may show the way forward towards reducing such burdens of disease treatment.





3 Gavin AT, Drummond FJ, Donnelly C, OLeary E, Sharp L, Kinnear HRPatient-reported ever had and current long-term physical symptoms after prostate cancer treatments. BJU Int 2015; 397406

John W. Davis, MD
Associate Editor, BJUI

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