Application of Various Techniques to Gain Insights Into the Complex Urinary Tract Microbial Communities of Renal Transplant Recipients.

Urinary tract infections (UTIs) are prevalent in renal transplant (RTX) recipients and associated with worse outcomes. Early detection by sensitive diagnostic tests and appropriate treatment strategies in this cohort is therefore crucial, but evidence has shown that current methods may miss genuine infections. Research has shed light on the urinary tract microbial ecology of healthy individuals and nontransplant patients with UTI, but information on the RTx cohort is scant. We conducted a cross-sectional study to (i) compare the gold standard diagnostic culture with alternative techniques and (ii) characterize RTx patient urinary microbial communities. Methods: Midstream urine specimens were collected from 51 RTx patients attending a renal transplant clinic and 27 asymptomatic controls. Urinary microscopy, dipstick, and routine culture were performed. To improve sensitivity of microbial detection, we cultured the urinary cell sediment and performed 16S rRNA gene sequencing on urine. Uroplakin-positive urothelial cells shed in urine were analyzed by immunofluorescence staining for any bacterial association. Results: Sediment culture and 16S rRNA sequencing confirmed detection deficiencies of diagnostic culture and revealed differences in the urobiomes of RTx patients and controls. Specifically, Gardnerella, Escherichia, and Lactobacillus were most abundant in patients, whereas Lactobacillus, Streptococcus, and Gardnerella were most abundant in controls. The application of both culture and sequencing provided a more nuanced view of the urinary microbial communities. Conclusions: This study provides insight into the potential problems of diagnostic culture within RTx patients and sheds light on their urinary microbial inhabitants. Further work may identify key microbial signatures and facilitate the development of better tools for UTI detection within this cohort, which could allow targeted intervention before an infection leads to serious consequences. http://links.lww.com/TXD/A479.

Evaluating the Quality and Readability of Online Resources on Unspecified Kidney Donation.

BACKGROUND: Unspecified kidney donation (UKD) refers to transplantation from donors unrelated and unknown to the recipient. UKD has contributed to the expansion of the live donor pool in several countries. The United Kingdom Transplant Community has set maximizing UKDs as a priority. The Internet raises awareness and potentially influences the decision-making regarding UKD. This is the first study assessing the quality and readability of online material on UKD. MATERIALS AND METHODS: Google was searched for the terms "kidney donation" and one of "unspecified," "altruistic," "non-directed," "anonymous," or "good Samaritan," as well as "giving or donating a kidney to a stranger." Two independent assessors reviewed the top 100 websites. Quality was assessed using the Journal of the American Medical Association criteria, the DISCERN instrument and Health On the Net Code certification. Readability was assessed using the Flesch Reading Ease (FRE), Flesch-Kincaid Grade (FKG), and Simple Measure of Gobbledygook (SMOG) scores. RESULTS: Only 6% of websites displayed HONcode certification. The mean (± SD) JAMA and DISCERN scores of 1.96 (± 1.00) and 32.34 (± 11.19) indicate poor quality. The mean (± SD) FRE, FKG, and SMOG scores of 52.92 (± 13.62), 10.60 (± 2.72), and 9.64 (± 2.22) reveal poor readability. The difference in JAMA and DISCERN scores according to website classification was significant (P < .001, P = .014) with websites from medical, nonprofit, and governmental organizations scoring amongst the lowest, while comprising most search results (61%). CONCLUSIONS: Transplant centers and medical organizations should prioritize improving their online resources to lower the risk of individuals pursuing UKD based on unrealistic expectations or being discouraged unjustly.

Contralateral inguinal herniation of a transplant ureter causing obstructive uropathy in a renal transplant recipient.

Ipsilateral inguinal herniation of the transplanted ureter has been reported as a rare cause of obstructive uropathy in renal transplant recipients. A 73-year-old man presented with acute renal failure 29 years after receiving a deceased donor renal transplant. Radiological investigations demonstrated marked hydronephrosis of the left iliac fossa transplant kidney and herniation of the distal transplant ureter and bladder into the right inguinal canal. The patient underwent placement of a nephrostomy and antegrade stent followed by definitive hernia repair with return of graft function to baseline level.

Anastrozole and letrozole: an investigation and comparison of quality of life and tolerability.

Previous studies have demonstrated that both anastrozole and letrozole are well tolerated. Letrozole suppresses estrogen to a greater degree than anastrozole in the serum and breast tumor. Concerns have been raised that greater potency may adversely affect patients' quality of life (QOL). One hundred eighty-one postmenopausal women with invasive estrogen receptor-positive breast cancers were randomized to receive either 12 weeks of letrozole followed by 12 weeks of anastrozole or the reverse sequence. One hundred and six received immediate adjuvant aromatase inhibitors (AIs) following surgery, and 75 received extended adjuvant therapy. The Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-B-ES) QOL questionnaires were completed to assess QOL on each drug. Additional side-effect profiles were collected. Each patient completed a patient preference form. Twenty-one patients withdrew before study end, 10/179 (5.6%) while taking letrozole and 4/173 (2.3%) while taking anastrozole (P = 0.12). Tamoxifen-naïve patients had a higher mean ES (endocrine symptoms subscale) score at entry versus those having extended therapy (66.0 vs. 61.9; P = 0.001). There was no significant change in FACT-B-ES (overall) scores or ES scores while patients were taking anastrozole or letrozole and no significant differences between drugs. Nearly 80% of patients reported one or more side effects with either agent. No differences in frequency, grade, or range of side effects were seen between drugs. Of 160 patients, 49 (30.6%) preferred letrozole, 57 (35.6%) preferred anastrozole, and 54 (33.8%) had no preference (P = 0.26, Pearson's Chi-squared test). In conclusion, both AIs are equally well tolerated. There were no significant differences in QOL scores between the two drugs.

A study of the effects of the aromatase inhibitors anastrozole and letrozole on bone metabolism in postmenopausal women with estrogen receptor-positive breast cancer.

ALIQUOT (Anastrozole vs. Letrozole, an Investigation of Quality Of Life and Tolerability) was a prospective, open-label, randomized pharmacodynamic study designed to assess the effects of aromatase inhibitors (AIs) on bone turnover in healthy postmenopausal women with estrogen receptor-positive breast cancer. Ninety-four patients were randomized to receive either 12 weeks of letrozole (2.5 mg; n = 42) followed by 12 weeks of anastrozole (1 mg), or 12 weeks of anastrozole (1 mg; n = 42) followed by 12 weeks of letrozole (2.5 mg). After completion of the study period, patients in the immediate adjuvant group were either switched to tamoxifen (n = 38) or continued on anastrozole or letrozole. In the beginning of the study, 42 patients had taken tamoxifen within 3 months. Patients taking drugs likely to affect bone metabolism, including bisphosphonates, were excluded. Eighty-four patients had complete sample measurements and were included in the analysis. Prior tamoxifen therapy resulted in a significantly lower mean baseline procollagen type 1 N-terminal propeptide (PINP) compared with patients with no prior tamoxifen. There were no significant differences in bone markers between AIs at any time. By 6 months, significant increases were seen in PINP, C-terminal telopeptides (CTX), bone specific alkaline phosphatise (ALP), and urinary N-terminal telopeptides (NTX). Patients with prior tamoxifen had significantly greater increases than patients with no prior tamoxifen. Patients treated with 3 months of tamoxifen following 6 months of an AI showed a significant decrease in markers of bone resorption, serum CTX and urinary NTX. In conclusion, AI-induced bone turnover increases over time. Anastrozole and letrozole produce similar effects on bone metabolism and turnover. Stopping tamoxifen therapy and starting AIs results in a significantly greater increase in bone turnover compared with commencing AIs in tamoxifen-naïve patients. Patients given tamoxifen following AI therapy showed a decrease in markers of bone resorption.