Investigation of smoking on the antiplatelet response to clopidogrel: Unravelling the smoker's paradox.

The intricate relationship between smoking and the effects of the antiplatelet drug clopidogrel has been termed the "smoker's paradox". This paradox details the enhanced efficacy of clopidogrel in smokers compared to non-smokers. This review begins with an exploration of the proposed mechanisms of the smoker's paradox, particularly drawing attention to the induction of cytochrome P450 (CYP) isoenzymes via tobacco smoke, specifically the enzymes CYP1A2 and CYP2C19. Moreover, an investigation of the effects of genetic variability on the smoker's paradox was undertaken from both clinical and molecular perspectives, delving into the effects of ethnicity and genetic polymorphisms. The intriguing role of CYP1A2 genotypes and the response to clopidogrel in smoking and non-smoking populations was examined conferring insight into the individuality rather than universality of the smoker's paradox. CYP1A2 induction is hypothesised to elucidate the potency of smoking in exerting a counteracting effect in those taking clopidogrel who possess CYP2C19 loss of function polymorphisms. Furthermore, we assess the comparative efficacies of clopidogrel and other antiplatelet agents, namely prasugrel and ticagrelor. Studies indicated that prasugrel and ticagrelor provided a more consistent effect and further reduced platelet reactivity compared to clopidogrel within both smoking and non-smoking populations. Personalised dosing was another focus of the review considering patient comorbidities, genetic makeup, and smoking status with the objective of improving the antiplatelet response of those taking clopidogrel. In summation, this review provides insight into multiple areas of research concerning clopidogrel and the smoker's paradox taking into account proposed mechanisms, genetics, other antiplatelet agents, and personalised dosing.

Determination of optimal stent length: a survey of urologic surgeons.

Introduction: Ureteral double-J stent length is an important factor affecting stent-related symptoms. Multiple techniques exist to determine ideal stent length for a given patient, however, little is known about what techniques urologists rely on. Our objective was to identify how urologists determine optimal stent length. Material and methods: An online survey was e-mailed in 2019 to all members of the Endourology Society. The survey sought to assess what methods are commonly used to determine choice of stent length, along with frequency of stent placement post ureteroscopy, duration of stenting, availability of different stent lengths and the use of stent tether. Results: 301 urologists (15.1%) responded to our survey. Following ureteroscopy, 84.5% of respondents would stent at least 50% of the time. Following uncomplicated ureteroscopy, most respondents (52.0%) would leave a stent for 2-7 days. Patient height was most commonly ranked first as the method of choice in determining stent length (47.0%), followed by estimation based on experience only (20.6%) and intra-operative direct measurement of ureteric length (19.1%). Most respondents utilized multiple methods in determination of optimal stent length. Most respondents (66.5%) were interested in a simple intra-operative technique utilizing a special ureteral catheter that would help choose the most appropriate stent length. Conclusions: Post-ureteroscopy stent insertion is common and patient height is the most common method of choice used in determining optimal stent length. Most respondents were interested in using a simple, novel ureteral catheter device that would allow them to more accurately select optimal stent length.

Comparison of Centrifugal and Pulsatile Perfusion to Preserve Donor Kidneys Using Ex Vivo Subnormothermic Perfusion.

Objective We have previously demonstrated benefits of kidney preservation utilizing an oxygenated subnormothermic ex vivo perfusion platform. Herein, we aim to compare pulsatile versus centrifugal (steady and uniform flow) perfusion with the goal of optimizing renal preservation with these devices. Materials and methods: Pig kidneys were procured following 30 min of warm ischemia by cross-clamping both renal arteries. Paired kidneys were cannulated and underwent either: oxygenated pulsatile or centrifugal perfusion using a hemoglobin oxygen carrier at room temperature with our ex vivo machine perfusion platform for 4 hr. Kidneys were reperfused with whole blood for 4 hr at 37° C. Renal function, pathology and evidence of inflammation were assessed post-perfusion. Results: Both pump systems performed equally well with organs exhibiting similar renal blood flow, and function post-reperfusion. Histologic evidence of renal damage using apoptosis staining and acute tubular necrosis scores was similar between groups. This was corroborated with urinary assessment of renal damage (NGAL 1) and inflammation (IL-6), as levels were similar between groups. Conclusion: In our porcine model with added warm ischemia simulating the effects of reperfusion after transplantation, pulsatile perfusion yielded similar renal protection compared with centrifugal perfusion kidney preservation. Both methods of perfusion can be used in ex vivo kidney perfusion systems.

Systematic Review of the Prevalence of Kidney Stones in Cystic Fibrosis.

Purpose: To investigate the prevalence of urolithiasis in cystic fibrosis (CF) and to summarize the available clinical features within this unique population. Methods: Studies reporting the prevalence of urolithiasis in CF patients were identified by a systematic search of the literature from inception to July 31, 2020 on three databases: Ovid Medline, Ovid Embase, and Web of Science. Data were extracted on a predetermined standardized form by two independent authors. Results: A total of 596 publications were retrieved and screened, 15 of which met the eligibility criteria. The publications were published between 1993 and 2019 and were all observational in design. There was a total of 2982 patients with CF included in this review. The overall prevalence of stone formation in the CF population was 4.6% (137/2982). The mean age of diagnosis was 25.1 ± 9.6 and ranged from 0.25 to 47. Ultrasound was the most common imaging modality for kidney stone diagnosis. There was no apparent sex difference, with a female to male ratio of 1:1. Surgical intervention was required in 37.8% (34/90) of cases. Stone recurrence was reported in 42.9% (33/77) of stone formers. Conclusions: This review provides the most recent update for the prevalence of urolithiasis in CF patients and summarizes the available clinical data. Our findings suggest that patients with CF could be at risk for developing stones at a younger age and require interventional management strategies at higher rates compared with the general population. Given the heterogeneity of the literature for urolithiasis in CF, larger population-based studies reporting the epidemiology, clinical features, and management strategies are required to further our understanding of urolithiasis in CF.

A review of routinely collected data studies in urology: Methodological considerations, reporting quality, and future directions.

Studies using routinely collected data (RCD) are common in the urological literature; however, there are important considerations in the creation and review of RCD discoveries. A recent reporting guideline (REporting of studies Conducted using Observational Routinely-collected health Data, RECORD) was developed to improve the reporting of these studies. This narrative review examines important considerations for RCD studies. To assess the current level of reporting in the urological literature, we reviewed all the original research articles published in Journal of Urology and European Urology in 2014, and determined the proportion of the RECORD checklist items that were reported for RCD studies. There were 56 RCD studies identified among the 608 articles. When the RECORD items were considered applicable to the specific study, they were reported in 52.5% of cases. Studies most consistently (>80% of them) reported the names of the data sources, the study time frame, the extent to which the authors could access the database source, the patient selection, and discussed missing data. Few studies (<25%) discussed validation of key coding elements, details on data-linkage, data-cleaning, the impact of changing eligibility over time, or provided the complete list of coding elements used to define key study variables. Reporting factors specifically relevant in RCD studies may serve to increase the quality of these studies in the urological literature. With increased technological integration in healthcare and the proliferation of electronic medical records, RCD will continue to be an important source for urological research.

Optimal management of distal ureteric strictures following renal transplantation: a systematic review.

Our objective was to define optimal management of distal ureteric strictures following renal transplantation. A systematic review on PubMed identified 34 articles (385 patients). Primary endpoints were success rates and complications of specific primary and secondary treatments (following failure of primary treatment). Among primary treatments (n = 303), the open approach had 85.4% success (95% CI 72.5-93.1) and the endourological approach had 64.3% success (95% CI 58.3-69.9). Among secondary treatments (n = 82), the open approach had 93.1% success (95% CI 77.0-99.2) and the endourological approach had 75.5% success (95% CI 62.3-85.2). The most common primary open treatment was ureteric reimplantation (n = 33, 81.8% success, 95% CI 65.2-91.8). The most common primary endourological treatment was dilation (n = 133, 58.6% success, 95% CI 50.1-66.7). Fourteen complications, including death (4 weeks post-op) and graft loss (12 days post-op), followed endourological treatment. One complication followed open treatment. This is the first systematic review to examine the success rates and complications of specific treatments for distal ureteric strictures following renal transplantation. Our review indicates that open management has higher success rates and fewer complications than endourological management as a primary and secondary treatment for post-transplant distal ureteric strictures. We also outline a post-transplant ureteric stricture evaluation and treatment algorithm.

Bilateral epididymitis in a child with undiagnosed posterior urethral valves.

Posterior urethral valves are most commonly detected in the early neonatal period, the diagnosis often antenatally suspected from ultrasound findings. Nevertheless, some cases might go undetected and become manifest later in life with lower urinary tract symptoms. We describe the unusual case of a 5-year-old boy with a 2-month history of bladder distension, urinary dribbling, and epididymitis. Cystourethrography revealed posterior urethral valves with reflux into the seminal vesicles, vas deferens, and epididymis, bilaterally. A review of the published data is provided in the context of this unusual presentation pattern.

Comparing baseline symptom severity and demographics over two time periods in an outpatient palliative radiotherapy clinic.

PURPOSE: The primary objective of this study was to compare the symptom severity in two different patient populations assessed in an outpatient palliative radiotherapy clinic over two time periods spanning 10 years. The secondary objective was to assess any changes in the baseline demographics of these patients. METHODS: Data were collected from 1999 to 2009. Upon initial presentation to the clinic, the Edmonton Symptom Assessment Scale (ESAS) was administered to patients to capture symptom severity. This validated assessment tool asks patients to score their level of pain, tiredness, nausea, depression, anxiety, drowsiness, loss of appetite, well-being, and dyspnea on an 11-point Likert scale. Differences between the two patient groups were assessed using chi-squared analysis and Wilcoxon rank-sum tests. A p value of <0.05 was considered significant. RESULTS: A total of 1,439 patients completed the ESAS from 1999 to 2009. Patients were divided into two time periods 1999-2002 (n = 689) and 2006-2009 (n = 750). Pain, depression, nausea, fatigue, anxiety, drowsiness, and dyspnea were significantly better in 2006-2009 (p < 0.0001). Loss of appetite was not statistically different between the two time periods (p = 0.236). Significantly more patients with genitourinary cancers (p = 0.03) or a referral for a mass (p < 0.0001) were seen in 2006-2009. More patients with breast cancer (p = 0.04) and bone pain (p = 0.0002) were seen in 1999-2002. The median age was significantly higher (70 years vs. 68 years, p = 0.03) for patients seen in 2006-2009. No significant differences were seen in performance status or gender between the two groups. CONCLUSION: There have been statistically significant lower scores in the severity of the majority of symptoms as scored by the latter patient cohort; however, whether this difference in magnitude is clinically significant is debatable. The reason for referral and demographics in patients sent for palliative radiotherapy has changed over a 10-year period. This may be a reflection of the changes in systemic therapies and improvements in supportive care for patients with advanced cancer.

Two paediatric cases of skin and soft-tissue infections due to clindamycin-resistant Staphylococcus aureus carrying a plasmid-encoded vga(A) allelic variant for a putative efflux pump.

Two clinical Staphylococcus aureus isolates were investigated due to their unusual antimicrobial susceptibility pattern, i.e. erythromycin-susceptible but clindamycin-resistant. These isolates harboured identical copies of a plasmid-borne vga(A)(LC) gene not previously described in S. aureus. The native plasmids carrying vga(A)(LC) were transferable to a susceptible laboratory strain of S. aureus in vitro, in which they conferred resistance patterns similar to the parent isolates.

Edmonton symptom assessment scale as a prognosticative indicator in patients with advanced cancer.

BACKGROUND: Few studies incorporate patient self-assessment scales in prognostic models of survival prediction. The Edmonton Symptom Assessment Scale (ESAS) is commonly used as a symptom screening tool in cancer patients. OBJECTIVE: The goal of this study was to evaluate the prognostic value of the ESAS for survival prediction in the advanced cancer population. MATERIALS AND METHODS: Patients completed the ESAS and demographic information prior to palliative radiotherapy consultation and at follow-up at the Odette Cancer Centre between 1999 and 2009. Generalized estimating equation (GEE) methodology was applied to analyze ESAS trends within the last months of life. One-way analysis of variance (ANOVA) with repeated measurements was used to characterize trends between time periods. RESULTS: ESAS records (2377) from 808 patients (433 male and 375 female) were included in this cohort. Median age was 68 years (range 32-95) with median Karnofsky performance status (KPS) of 60 (range 10-100). Primary cancer sites were of the lung (36%), breast (20%), and prostate (19%). All nine ESAS symptoms significantly deteriorated in the last 4 weeks immediately before death when compared with those scores in the preceding months. At one week prior to death, the worst ESAS symptoms experienced by patients were fatigue, appetite, and well-being with mean scores of 7.4, 6.9, and 6.1, respectively. CONCLUSIONS: All ESAS scores significantly worsened in the last 4 weeks prior to death compared with those in the previous months. Sudden deterioration of the global ESAS symptoms may predict impending death. Future studies on a prognostic model should incorporate both ESAS symptom severity and trends.

Prevalence and mechanisms of broad-spectrum beta-lactam resistance in Enterobacteriaceae: a children's hospital experience.

The objective of this study was to investigate the trends and patterns of resistance in beta-lactamase-producing members of the family Enterobacteriaceae in a children's hospital over a 9-year period (1999 to 2007). Clinically significant isolates of the Enterobacteriaceae were screened for patterns of broad-spectrum resistance to beta-lactams. The strains likely to be resistant were subsequently confirmed by an inhibitor-based disc test. The plasmid-mediated resistance determinants in these isolates were identified by PCR and by in vitro transformation, which successfully reproduced the AmpC phenotype unrestricted by the species of the host organisms. Among 8,048 Enterobacteriaceae isolates belonging to the four chromosomal ampC-negative or -nonfunctional genera, 86 (1.07%) isolates (56 Escherichia coli isolates, 22 Klebsiella species isolates, 1 Proteus mirabilis isolate, and 7 Salmonella species isolates) exhibited broad-spectrum beta-lactam resistance patterns. These organisms collectively produced three classes of beta-lactamases, including class A extended-spectrum beta-lactamases (n = 47), class C or AmpC beta-lactamases (n = 36, including 4 isolates that produced both class A and class C enzymes), and class A or B carbapenem-hydrolyzing beta-lactamases (n = 3). The proportion increased from 0.46% during the first 3 years to 1.84% during the last 3 years (relative risk [RR], 4.04; 95% confidence interval [CI], 2.28 to 7.42; P < 0.001). The increase was mainly due to the emergence of a plasmid-mediated bla(CMY-2) beta-lactamase, the incidence of which increased from 0.11% during the first 3 years to 0.96% during the last 3 years (RR, 9.11; 95% CI, 2.76 to 30.1; P = 0.001). Class A-type resistance increased slightly during the study period, from 0.35% during the first 3 years to 0.85% during the last 3 years (RR, 2.42; 95% CI, 1.15 to 5.07; P = 0.02). A Proteus mirabilis strain was documented to possess a novel bla(DHA) determinant. Of special concern, three carbapenemase-producing isolates were identified between 2003 and 2006. The infections caused by resistant isolates of the Enterobacteriaceae mainly affected hospitalized patients with underlying conditions; however, 19 (22%) episodes were of community onset in otherwise well children. The rate of resistance to broad-spectrum beta-lactams among isolates of the Enterobacteriaceae is increasing in children in both hospital- and community-acquired settings, and the resistance is driven largely by plasmid-mediated AmpC beta-lactamases. These data have important implications for empirical antimicrobial strategies targeting serious pediatric infections. Further study of this problem is warranted.