Evaluation of efflux pump inhibitory activity of some plant extracts and using them as adjuvants to potentiate the inhibitory activity of some antibiotics against Staphylococcus aureus.

Background: Antibiotic-resistant pathogens became a real global threat to human and animal health. This needs to concentrate the efforts to minimize and control these organisms. Efflux pumps are considered one of the important strategies used by bacteria to exclude harmful materials from the cell. Inhibition of these pumps can be an active strategy against multidrug resistance pathogens. There are two sources of efflux pump inhibitors that can be used, chemical and natural inhibitors. The chemical origin efflux pump inhibitors have many toxic side effects while the natural origin is characterized by a wide margin of safety for the host cell. Aim: In this study, the ability of some plant extracts like (propolis show rosemary, clove, capsaicin, and cumin) to potentiate the inhibitory activity of some antibiotics such as (ciprofloxacin, erythromycin, gentamycin, tetracycline, and ampicillin) against Staphylococcus aureus pathogen were tested. Methods: Efflux pump inhibitory activity of the selected plant extracts was tested using an ethidium bromide (EtBr) accumulation assay. Results: The results have shown that Propolis has a significant synergistic effect in combination with ciprofloxacin, erythromycin, and gentamycin. While it has no effect with tetracycline or ampicillin. Also, no synergic effect was noticed in a combination of the minimum inhibitory concentration for the selected plant extracts (rosemary, clove, capsaicin, and cumin) with any of the tested antibiotics. Interestingly, according to the results of the EtBr accumulation assay, Propolis has potent inhibitory activity against the S. aureus (MRS usa300) pump system. Conclusion: This study suggests that Propolis might act as a resistance breaker that is able to restore the activity of ciprofloxacin, erythromycin, and gentamycin against S. aureus strains, in case of the efflux-mediated antimicrobial resistance mechanisms.

Retzius-sparing technique independently predicts early recovery of urinary continence after robot-assisted radical prostatectomy.

Robot-assisted radical prostatectomy (RARP) is the conventional surgical treatment option for localised prostate cancer. We investigated factors which may be associated with recovery of early urinary continence (EUC), including the use of the Retzius-sparing technique (RS-RARP). From March 2018 to December 2018, 501 consecutive patients underwent RARP at our high-volume institution. Four hundred and thirty-one patients had complete follow-up data and were included in our analyses. EUC was defined as zero pad use and social urinary continence (SUC) was defined as ≤ 1 pad/24-h period at 3 months following surgery. Patient demographics and clinical factors such as age, body mass index (BMI), neurovascular bundle (NVB) sparing, RS-RARP operative technique and operating surgeon (consultant, trainee) were recorded. Median age was 64.0 years (IQR 57.0-69.0 years) with a median BMI of 27.0 (IQR 25.0-29.9). RS-RARP accounted for 59 of the 431 (13.7%) patients. 196 (45.5%), 142 (32.9%) and 86 (20.0%) received a bilateral, unilateral and nil NVB sparing, respectively. EUC was achieved by 241 patients (55.9%) and SUC was achieved in 339 (78.7%) patients. Multivariable logistic regression analysis suggests younger age (HR 1.04, 95% CI 1.01-1.07, p = 0.014) and RS-RARP technique (HR 2.19, 95% CI 1.15-4.16, p = 0.017) were independently associated with EUC at 3 months even after adjusting for BMI, external membranous urethral length and NVB sparing. Our results suggest that RS-RARP technique is independently predictive of EUC even after accounting for confounding factors. These findings should be further validated in a prospective or randomised trial.

Effects of Delayed Radical Prostatectomy and Active Surveillance on Localised Prostate Cancer-A Systematic Review and Meta-Analysis.

External factors, such as the coronavirus disease 2019 (COVID-19), can lead to cancellations and backlogs of cancer surgeries. The effects of these delays are unclear. This study summarised the evidence surrounding expectant management, delay radical prostatectomy (RP), and neoadjuvant hormone therapy (NHT) compared to immediate RP. MEDLINE and EMBASE was searched for randomised controlled trials (RCTs) and non-randomised controlled studies pertaining to the review question. Risks of biases (RoB) were evaluated using the RoB 2.0 tool and the Newcastle-Ottawa Scale. A total of 57 studies were included. Meta-analysis of four RCTs found overall survival and cancer-specific survival were significantly worsened amongst intermediate-risk patients undergoing active monitoring, observation, or watchful waiting but not in low- and high-risk patients. Evidence from 33 observational studies comparing delayed RP and immediate RP is contradictory. However, conservative estimates of delays over 5 months, 4 months, and 30 days for low-risk, intermediate-risk, and high-risk patients, respectively, have been associated with significantly worse pathological and oncological outcomes in individual studies. In 11 RCTs, a 3-month course of NHT has been shown to improve pathological outcomes in most patients, but its effect on oncological outcomes is apparently limited.

Local Anesthetic Flexible Ureterorenoscopy in the Management of Urolithiasis.

Introduction: Patients unfit for general anesthesia who present with renal tract pathology currently have limited options. Many of these patients present in the emergency setting with imperative reasons for intervention, including sepsis, renal failure, and pain. Conservative management and temporizing measures, such as percutaneous nephrostomy, are associated with significant morbidity. Ureterorenoscopy (URS) is a central component of the management of upper tract disease and is routinely performed under general anesthesia. We describe our institution's experience of URS using only local anesthetic (LA) lubricating gel per urethra. Methods: A single centre, retrospective analysis of 78 patients was performed for an 11 year period. Demographic data and Charlson comorbidity index scoring were collected for all patients. Outcomes, including stone-free rates, tolerability, and complications, were analyzed. Results: In total 58% of patients were men. Mean age was 68 and Charlson comorbidity index was 5.2. Indications for URS included pain (68%) and renal failure (15%). Totally 10% of patients previously had retrograde stenting because of sepsis. Median stone size was 8 mm. All patients were able to tolerate the procedure and none were abandoned because of pain. The overall stone-free rate was 82% after one procedure. The stone-free rate for mid and distal ureteral stones was 97%. Nineteen percent of patients were left with a ureteral stent after the procedure, with the remaining patients left totally tubeless. Median length of stay was 1 day. There were no complications above Clavien Grade 2. Conclusion: Urologists are increasingly faced with unfit patients presenting with urolithiasis. In the appropriately selected patient, LA flexible ureterorenoscopy is a feasible option with good outcomes. This approach is a useful addition to the armamentarium available to patients deemed unsuitable for general or regional anesthesia.

Accelerating Adoption of Patient-Facing Technologies in Clinical Trials: A Pharmaceutical Industry Perspective on Opportunities and Challenges.

BACKGROUND: Patient-facing digital technologies (also called "Patient Technology" [PT]) have the potential to serve a variety of functions in clinical trials, such as capturing clinical endpoints, engaging patients, and facilitating remote study conduct. However, these technologies are not yet accepted as mainstream research tools, and the opportunities, challenges, and facilitators associated with their implementation in clinical trials have not been fully characterized. METHODS: In order to understand the factors affecting PT adoption, the TransCelerate Patient Technology Initiative conducted a series of surveys, interviews, and focus groups with approximately 600 subject matter experts, including pharmaceutical company representatives, clinical trial investigators at a number of trial sites worldwide, and clinical trial participants. All interview and survey responses were blinded and aggregated by a third-party consultant and themes were extracted. RESULTS: There was general consensus around the potential value of patient-facing technology as a clinical research tool, though a variety of challenges faced by each stakeholder were discussed. Detailed accounts of opportunities (improved patient experience, compliance, and engagement; clinical trial efficiencies; improved data quality and insights) and barriers (organizational and corporate cultural challenges, business-related challenges, user willingness and burden, and regulatory challenges) are reported. CONCLUSIONS: While the barriers to PT adoption explored here were numerous, they were also generally consistent. A number of proposals for establishing more holistic, collaborative, and strategic approaches to PT implementation in clinical trials are discussed. Such approaches could facilitate more effective, widespread adoption of PT, and thereby a more patient-centric clinical trial paradigm.