Cheryl Guttman Krader is a contributor to Dermatology Times, Ophthalmology Times, and Urology Times.

Cheryl Guttman Krader, BS, Pharm

Findings from a systematic review and meta-analysis of urosepsis after ureteroscopy (URS) for stone management show that this serious complication occurs at an unexpectedly high rate and is associated with some surprising risk factors, according to investigators.

The research, which is the first systematic review with meta-analysis to specifically investigate risk factors for and incidence of urosepsis after URS, analyzed data from 13 studies that included 5597 patients.1 It found a 5% pooled incidence of postoperative urosepsis and determined that preoperative stent placement, positive preoperative urine culture, older age, diabetes, longer procedure time, and ischemic heart disease were each associated with a statistically significant increased risk.

“Ureteroscopy has become the leading approach for treating stone disease because of its efficacy and the perception that it is a very safe procedure and associated with minimal morbidity. Therefore, the 5% rate of urosepsis was surprising to us and to other urologists as well, judging from posted tweets,” lead author Naeem Bhojani, MD, told 

Bhojani and senior author Ben H. Chew, MD, MSc, pointed out that although their study identified associations between certain variables and urosepsis risk, it does not establish causal relationships. For that reason and in the absence of evidence about the efficacy of preventive strategies targeting these factors, it is not possible to make any recommendations for risk management.

“Nevertheless, we believe our findings can be useful for urologists in preoperative risk stratification and for guiding the intensity of postoperative surveillance,” said Chew, an associate professor in the Department of Urologic Sciences at the University of British Columbia in Vancouver, Canada.

The 13 studies used for the meta-analysis included 5 prospective trials. Across the 13 studies, the rate of urosepsis ranged from 0.2% to 17.8%. The use of different criteria for urosepsis diagnosis and different durations of postoperative symptom surveillance (1 to 30 days) may, in part, account for the wide variability in rate, said Bhojani, a principal scientist, urologist, and associate professor at the University of Montreal in Canada.

Although surprisingly high, the 5% rate of urosepsis appears to be true. In a follow-up investigation, the investigators turned to the IBM MarketScan Commercial Database that contained information from over 110,000 URS procedures performed in the United States. In that large cohort of cases with prospectively collected data, they found a nearly identical 30-day postoperative sepsis rate of 4.91%.

Pre-op stent placement, older age were among risk factors

In the meta-analysis, preoperative stent placement, positive preoperative urine culture, and older age were the strongest risk factors for postoperative urosepsis. The effects of having a stent or a positive urine culture are easy to understand because patients with these findings are likely colonized with bacteria or have bacteriuria, Bhojani said.

The association with ischemic heart disease, however, was particularly surprising and hard to rationalize. Explanations for the associations between urosepsis and older age, diabetes, and longer procedure time are also unclear, although Bhojani postulated that increasing procedure time could favor translocation of bacteria into the bloodstream because it would be accompanied by an increasing level of intrarenal pressure.

“There are some observational data suggesting that exposure to a longer duration of increased intrarenal pressure can lead to infection being transmitted into the bloodstream, and we are currently studying that relationship further,” Bhojani said.

Chew noted that large prospective studies would be needed to determine effective ways for reducing urosepsis risk.

“Based on our study, we cannot say that patients with the risk factors we identified should be given more powerful antibiotics as prophylaxis or kept in the hospital longer so that they can be watched more closely for postoperative sepsis,” he said. “However, we think that urologists should remain aware that patients with 1 or more of the risk factors warrant more intensive monitoring because they may be at significant risk for urosepsis after URS.”

1. Bhojani N, Miller LE, Bhattacharyya S, Cutone B, Chew BH. Risk factors for urosepsis after ureteroscopy for stone disease: a systematic review with meta-analysis. 

. Published online March 15, 2021. doi:10.1089/end.2020.1133

Articles

Review of nearly 5600 patients found a 5% pooled incidence of postoperative urosepsis.

Meta-analysis generates surprising insights on postureteroscopy urosepsis

Analyses of cross-sectional data from women participating in a Danish population-based study provide a reference for the prevalence of urinary incontinence (UI) among Western European women and support the hypothesis that because of disease-related complications, UI is more prevalent in women with diabetes than in women without diabetes, according to the investigators who published their results in a recent article.

The research included data collected through questionnaires and blood tests for 7906 adult women (aged ≥18 years) who were participants in the Lolland-Falster Health Study. The study population included 374 women with diabetes (4.7%) and 7532 women without diabetes (95.3%). UI, defined as any involuntary leakage of urine during the previous 4 weeks, was present in 188 (50.3%) of the women with diabetes and in 2958 (39.3%) of the women without diabetes.

An association between diabetes and UI was found in an unadjusted logistic regression analysis, with the odds of having UI being 56% higher among women with diabetes than in women without diabetes. Although no association was found between diabetes and UI in a multiple logistic regression analysis adjusting for confounders, there was an association between diabetes and more frequent UI in a subgroup multivariable logistic regression analysis. In addition, the results of another subgroup analysis with adjustment for confounders showed an association between having severe diabetes, identified based on use of multiple antidiabetic medications, and UI. The latter finding led investigators to comment that attention be given to UI when counseling women with severe diabetes.

Additional analyses evaluated associations between diabetes and UI subtypes: stress urinary incontinence, urgency urinary incontinence, and mixed urinary incontinence (MUI). When adjusting for confounders, diabetes was found to be significantly associated only with MUI. The investigators postulated this may be because diabetic women have more severe UI than women without diabetes.

Subgroup analyses stratifying women by hemoglobin A1c (HbA1c) level and duration of diabetes showed no clear patterns for risk. Age and body mass index were identified as the most important UI risk factors. Associations were also found between UI and parity, current smoking, and sedentary level of physical activity.

The investigators noted that previous studies have shown a link between diabetes and UI, and they hypothesized that such an association exists because diabetes-related microvascular complications and neuropathy would lead to bladder damage and/or affect detrusor muscle function. Nevertheless, previous studies investigating diabetes as a risk factor for UI have generated conflicting findings. The investigators noted that the variable results may be explained by differences in study populations, methods, and UI definitions.

In the current study, women were identified as having diabetes if they self-reported the diagnosis or use of insulin or another antidiabetic medication, had an HbA1c level of 6.5% or higher, or met criteria for history of filling prescriptions for an antidiabetic medication prior to study enrollment. The presence of UI and its subtypes was identified based on information from the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form.

According to the investigators, study strengths included a more than 90% questionnaire response rate and the ability to adjust for important confounders. They observed, however, that there was a risk of selection bias, as participation rates were lower for younger and older women. As another limitation, the investigators mentioned that the low number of women with diabetes and UI could have resulted in a type 2 error, and they reported that a post hoc sample size calculation revealed that the study had low power to detect an association.

1. Løwenstein E, Jepsen R, Andersen LL, et al. Prevalence of urinary incontinence among women with diabetes in the Lolland-Falster Health Study, Denmark. 

. 2021;40(3):855-867. doi:10.1002/nau.24636.

Odds of having UI were 56% higher in women with vs women without diabetes.

Urinary incontinence prevalence is higher in women with diabetes

Depression is common among individuals with Peyronie disease (PD), according to findings of a retrospective study.

The study, which was reported in an article published online by 

, aimed to identify factors that could predict depression among individuals seeking evaluation for early PD. Analyses comparing depressed and nondepressed cohorts categorized by scores on the validated Center for Epidemiologic Studies Depression Scale (CES-D) found no statistically significant differences between the 2 groups in any of the demographic-, bother-, or curve-related characteristics that were assessed as potential predictors. Notably, however, the depressed cohort represented 27% of the 408 study participants.

“There have been just 2 previous reports investigating the direct impact of PD on mental health, and they only briefly explored potential predictors of mental illness in this patient population. Given the limited data and the importance of this association, we undertook this study to determine if there were any characteristics that might help clinicians identify men with PD who are [experiencing] depression,” said Nahid Punjani, MD, MPH, first author of the published report, in an interview with 

“Although we did not identify any demographic-, bother-, or curve-related risk factors, we hope our study will lead urologists to acknowledge there is a high prevalence of depression in men with PD and to initiate an appropriate referral to a mental health care professional when indicated,” added Punjani, who is a fellow in male sexual medicine at Memorial Sloan Kettering Cancer Center and a fellow in reproductive medicine and instructor of urology at Weill Cornell Medical College in New York City, New York.

The investigators retrospectively reviewed prospectively collected data from patients with documented PD seen by a single provider, John P. Mulhall, MD, director of the Male Sexual and Reproductive Medicine Program at Memorial Sloan Kettering Cancer Center.

To be eligible for inclusion, participants needed to have undergone a curvature assessment upon intracavernosal injection at the time of duplex ultrasound and have completed 3 questionnaires that all patients with PD are asked to fill out at initial presentation: the Self-Esteem and Relationship (SEAR) questionnaire, which assesses the psychosocial impact of erectile dysfunction (ED); the Peyronie’s Disease Questionnaire (PDQ), which assesses the psychosexual consequences of PD; and the CES-D, which is used to screen for depression/depressive disorder. Patients with a CES-D score of 16 or higher were categorized as having clinically meaningful depression and comprised the depressed group.

“Dr Mulhall uses the CES-D as part of a highly structured, standardized intake for patients seeking evaluation for PD. Urologists, however, may employ any validated depression screening questionnaire to identify men with PD who may be depressed. They might also consider closely collaborating with a mental health professional at their institution,” Punjani said.

The 408 participants had a mean age of approximately 56.5 years and mean duration of PD of approximately 20 months. Features that differed significantly between the depressed and nondepressed groups included being partnered (83.9% vs 73.6%, respectively), having a history of depression (26% vs 11%, respectively), and mean degree of curvature (38° vs 33°, respectively). The latter difference, however, was not considered clinically meaningful, and the percentage of participants with a complex deformity was similar in the 2 groups. The depressed group also had significantly worse PDQ and SEAR scores than the nondepressed group.

Risk factors for depression were examined through logistic regression modeling. The multivariable models considered age, partner status, duration of PD, history of depression, complexity of deformity, PDQ domain scores, total SEAR score, and ED as potential predictors. Only the total SEAR score was independently associated with depression—having a higher (more favorable) SEAR score was protective against depression. The investigators noted that the SEAR questionnaire has not been validated in the PD population.

“Moving forward with research to understand the psychological and emotional impacts of PD, we hope to explore issues related to partner distress in this patient population,” Punjani said.

1. Punjani N, Nascimento B, Salter C, et al. Predictors of depression in men with Peyronie’s disease seeking evaluation. 

. Published online March 9, 2021. doi:10.1016/j.jsxm.2021.02.002

Depression appears to be common in patients, retrospective data indicate.

Study highlights negative mental health impact of Peyronie disease

Findings from a retrospective review of men who underwent 

F-fluciclovine (FACBC) PET/CT imaging for biochemically recurrent prostate cancer following curative intent local therapy provide real world insight into its performance characteristics and impact on treatment management, reported investigators from the University of North Carolina, Chapel Hill.

Their single-center study included 103 men, of whom 77 (75%) had lesions consistent with prostate cancer recurrence detected by FACBC PET/CT. The sites identified by the imaging most commonly occurred outside the pelvis (48%).

Stratification of men based on prostate-specific antigen (PSA) showed the likelihood of having a positive FACBC PET/CT increased with increasing PSA level. Yet recurrent disease was detected in more than one-third of men with a PSA less than 1 ng/mL.

The clinical impact of the imaging was assessed in a subgroup of 34 men post prostatectomy who had undergone conventional imaging. Within this cohort, 15 men (44%) had a change in recommended radiotherapy based on the findings from FACBC PET/CT imaging; the recommendation was to increase the dose in 11 men and was changed from treatment to palliative therapy in 4 men.

“FACBC PET/CT imaging for staging biochemically recurrent prostate cancer is endorsed by national guidelines, but there are limited studies investigating its performance and how its findings may affect treatment decision-making,” said Marc A. Bjurlin, DO, MSc, associate professor of urology, University of North Carolina.

“Our study further defines the performance characteristics of FACBC PET/CT imaging and supports its use for evaluating men with biochemically recurrent prostate cancer, even at low PSA thresholds,” Bjurlin added.

Of the 103 men in the study, 64 had undergone prostatectomy with curative intent and 37 were patients post radiation. The FACBC PET/CT detection rate was similar in the 2 groups. Median PSA for the entire cohort at the time of FACBC PET/CT imaging was 2.7 ng/mL (range, 0-67.4 ng/mL) and was less than 1 ng/mL in 31 men, 1 to less than 2 ng/mL in 11 men, and greater than 2 ng/mL in 61 men. The FACBC PET/CT positivity rates in the 3 PSA subgroups were 35.5%, 63.6%, and 96.7%, respectively. Among men with a PSA less than 1 mg/mL, the detected site of involvement was extraprostatic/extrapelvic in 45.5%.

Recurrent disease can be detected at low PSA thresholds

“These results highlight that in men with suspected biochemically recurrent prostate cancer, FACBC PET/CT can detect recurrent disease at low PSA thresholds. Utilizing a lower PSA threshold of 1.0 ng/mL as the trigger for this imaging may allow recurrent disease to be identified early while disease remains in an oligometastatic state and salvage interventions may remain an option,” Bjurlin said.

He continued, “Considering that recurrence outside of the pelvis was so common in our series, future studies may consider investigating a role for extending whole pelvis radiation therapy volumes to increase coverage of superior nodal regions. Additionally, patients may benefit from investigation of metastasis-directed therapies, including stereotactic ablative radiotherapy to treat nodal disease. The emerging fields of radiomics and radiogenomics could provide important prognostic information and aid decision making for patients with recurrent prostate cancer.”

In December 2020, the FDA approved Gallium 68 PSMA-11 for imaging in men with suspected prostate cancer metastasis who are potentially curable through surgery or radiation therapy and for those with suspected recurrence based on an elevated PSA level.

“Compared with FACBC, Gallium 68 PSMA-11 appears to further increase the detection of metastatic disease and can impact patient management. We are now studying the performance characteristics of this new radiotracer at our institution,” Bjurlin said.

Bjurlin acknowledged Jamie Michael, BS, University of North Carolina medical student and first author of the published article, for drafting the paper.

1. Michael J, Khandani AH, Basak R, et al. Patterns of recurrence, detection rates, and impact of 18-F Fluciclovine PET/CT on the management of men with recurrent prostate cancer. 

 Published online January 29, 2021. doi:10.1016/j.urology.2021.01.038

Findings support the modality’s use in biochemically recurrent prostate cancer, investigator says.

Cheryl Guttman Krader, BS, Pharm

Articles

Meta-analysis generates surprising insights on postureteroscopy urosepsis

Urinary incontinence prevalence is higher in women with diabetes

Study highlights negative mental health impact of Peyronie disease

Study assesses clinical value of FACBC PET/CT imaging in prostate cancer