Intravesical administration of durvalumab to patients with high risk non muscle invasive bladder cancer after BCG failure. A phase II trial by the Hellenic GU Cancer Group

Introduction & Objectives: Patients with high risk non muscle invasive bladder cancer (NMIBC) who experience BCG failure have limited bladder preserving treatment options as radical cystectomy currently represents the standard therapeutical approach. Systematic immunotherapy (IO) has changed the landscape in advanced bladder cancer and is currently being investigated in NMIBC. Based on the hypothesis that intravesical administration will not be related with severe adverse events, we evaluated the role of intravesically administered durvalumab in NMIBC patients after BCG failure. Material(s) and Method(s): An open label, single-arm, multi-center, phase II clinical trial was conducted. A run-in phase had the objective to determine the maximum tolerated dose (MTD) of durvalumab and to exclude a detrimental effect on disease relapse by this strategy. Durvalumab was administered for a total of 6 instillations per patient at consecutive levels of 500, 750 and 1000 mg. Phase II has as primary end point the 1-year high-grade-relapse-free (HGRF)-rate. Secondary endpoints included toxicity, and high-grade progression-free rat at 1, 3 and 6 months after treatment. Result(s): Thirty patients were enrolled (run in phase: 9, phase II: 21). One patient withdrew consent prior to receiving study treatment, so 29 patients were included in efficacy and toxicity analyses. Mean age was 66.5 years. MTD of durvalumab was set at 1000 mg as no dose related toxicities (DLTs) occurred at any level studied. Three of 9 patients included in the run-in phase (33.3%) were tumor free one month after the last durvalumab instillation, therefore, the null hypothesis was rejected by the futility analysis. Western blot showed that durvalumab remained stable in urine during instillation. One patient died from Covid-19, 3 months after the last durvalumab administration. All patients concluded at least 1 year follow up. One-year HGRF rate was 34.6%. HGRF rates at 1, 3 and 6 months was 73%, 65.3% and 50% respectively. Five patients (17%) experienced a T2 or above disease relapse. Five out of the six patients who received 500mg or 750mg of durvalumab relapsed within 1 year. When efficacy analyses were restricted to patients receiving 1000mg of durvalumab, 1-year HGRF rate was 35%. Interestingly, 2 out of 2 patients with only CIS disease at baseline experienced a tumor complete response, which was durable and was maintained at least for a year. No severe adverse events were noted. The most common adverse event was Grade 1 hematuria. Conclusion(s): Intravesical IO using durvalumab was proved to be feasible with an excellent safety profile. Oncological results seem to be promising and comparable with other bladder preserving strategies in BCG failure with the advantage of a better safety profile. Further study of intravesical IO in high-risk patients with NMIBC after BCG failure is warranted.Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.

THE EFFECT OF COMMON SURGICAL MASKS ON UNATTENDED BLOOD PRESSURE CHANGES IN DRUG TREATED HYPERTENSIVE PATIENTS

Objective: While there are several studies that have focused on the role of face masks in preventing airborne transmission of SARS-CoV-2, few data are available on their effects on physiological measures, and no study has examined their effects on blood pressure (BP). The purpose of our study was to investigate the effect of surgical masks on BP in drug-treated hypertensive patients who had a routine follow-up visit to a university hospital outpatient hypertension clinic. Design and method: The study included already treated hypertensive patients aged > 18 years, while the exclusion criteria were atrial fibrillation or any other arrhythmia affecting the BP measurement, an arm circumference > 42 cm, mental disorders, Parkinson disease, pregnancy, intolerance to the BP measurement method, or unwillingness to participate. A new surgical mask was provided to all participants to replace the face mask that was already in use. After the routine mask-on office BP measurement, patients were left alone and randomized to automated office BP measurement, with measurements taken after first wearing a mask for 10 min, then without wearing the mask for 10 min, and vice versa. Results: A total number of 265 patients were included in the study. Among the participants, 115 were women (43.4%), the mean age was 62 ± 12 years, and the mean office BP was 134 ± 15 / 81 ± 12 mmHg. There was no significant difference between mask-on unattended systolic BP (133 ± 15 mmHg) and mask-off unattended systolic BP (132 ± 15 mmHg) (P = 0.13) or between mask-on unattended diastolic BP (77 ± 13 mmHg) and mask-off unattended diastolic BP (76 ± 13 mmHg) (P = 0.32). Moreover, there was no difference in the heart rate (mask-on first, 69 ± 11 bpm;mask-off first, 69 ± 11 bpm, P = 0.7). Conclusions: Common surgical masks do not affect systolic/diastolic BP levels during unattended BP measurements in treated hypertensive patients.

IS ARTERIAL HYPERTENSION A MODIFIER OF CARDIOPULMONARY EXERCISE TEST AND ECHOCARDIOGAPHIC FINDINGS AFTER HOSPITALIZATION FOR SARS-COV-2?

Objective: There is little data concerning the impact of arterial hypertension (HTN) on the cardiopulmonary status and right ventricle (RV) function of patients with SARS-Cov-2 infection. The purpose of our study was to investigate whether HTN affects the functional status of hospitalized for SARS-Cov-2 patients, using cardiopulmonary test and echocardiographic parameters, 3 months after the first day of infection. Design and Method: Subjects who were hospitalized and survived Covid-19 infection were divided into two groups according to history of HTN. All subjects underwent cardiorespiratory exercise using Bruce or modified Bruce protocol evaluating all parameters. Echocardiographic findings including right ventricle strain were analyzed using an offline program. Results and Conclusion: A total population of 52 hospitalized Sars-Cov-2 patients with a mean age of 57 ± 11.5 years were evaluated 3 months after the symptoms onset. Males amounted to 51.9 %. History of coronary artery disease was recorded in 15.4% of them. In hypertensive subjects, age (63 ± 8 vs. 52 ± 11 years, p < 0.001), BMI (29.9 ± 4.6 vs. 27.1 ± 5.8 kg/m2, p:0.03) and BSA (2.1 ± 0.25 vs. 2 ± 0.9 m2, p:0.04) were significantly higher. When analyzing cardiopulmonary test parameters, only maximum systolic blood pressure ((SBP, mmHg), 190 ± 21 vs.171 ± 26, p: 0.02) at peak and during the 1st minute of recovery (180 ± 23 vs. 157 ± 27 mmHg, p: 0.005) were higher comparing to normotensive subjects. Furthermore, diameter of left atrium ((LA, mm), 42 ± 6 vs.38 ± 6 p: 0.009), left ventricle ejection fraction ((LVEF,%), 48 ± 11 vs. 57 ± 6, p:0.004) and the absolute mean value of right ventricle strain ((RVLS, %), 9.1 ± 4 vs. 12.7 ± 5.4, p:0.04) differed significantly between two groups. Using linear regression analysis adjusted for age, gender, HTN, coronary heart disease and LVEF, HTN (p: 0.01) proved to be independent predictive factor for RVLS in hospitalized patients. To conclude our study highlighted negative impact of HTN both in right and left ventricle functionality, implying HTN as a negative independent predictive factor for right ventricle strain in patients hospitalized for SARS-Cov-2.

Urology residency training during the pandemic. A review of the current literature

Introduction & Objectives: On March 11, 2020, WHO declared Covid-19 as a pandemic placing a significant strain on the worldwide healthcare system. Although urology does not stand at the frontline of care for patients with Covid-19, every practicing urologist has been affected by the global outbreak. The objective of this review is to evaluate the impact of Covid-19 pandemic on urology residency training programs. Materials & Methods: We performed a literature review of the current evidence on urology residency training during the Covid-19 pandemic. Relevant databases (MEDLINE, Scopus, Cochrane Library) were searched (until June 2021) and the main study-inclusion criterion was the presence of residents’ or directors’ opinion on their residency training program during the Covid-19 crisis. Results: Literature search identified 72 articles. 14 studies comprising a total of more than 2500 residents were eligible for inclusion in the analysis. During the pandemic, learning activities carried out by urology residents suffered a forced modulation. There has been a decrease in operation volume especially in procedures in which residents were directly involved. Similarly, there was a decline in most of the academic activities worldwide. Furthermore, the negative impact on residents’ mental well-being and lifestyle is reported by many studies. On the other hand, the lockdown stressed the opportunity to review the current training system and to increase the implementation of tools such as telemedicine and smart-learning surgical skill training programs. Conclusions: Covid-19 pandemic has resulted in significant changes in urology residency programs worldwide, with a negative impact on matters such as surgical training and academic activities. Residents’ well-being and mental health is also risked. Hopefully, this unprecedented situation has generated new online learning modalities and technological innovations in the field of training in urology

Dobutamine stress echocardiography during covid-19 pandemic: impact on volume and positivity rates in a tertiary hospital

Introduction: The emergence of coronavirus 2019 infection (covid-19) was accompanied by severe social and economic restrictions and applied significant pressure to the healthcare systems. The first pandemic wave started in March to May 2020 and was characterized by the peak of confinement measures and lockdown application. The second wave started in September and peaked in November to December 2020 and was characterized by improved healthcare organization but significant burden for the hospitals and intensive care units. Dobutamine stress echocardiography (DSE) is used for evaluation of ischemia in patients with known or suspected coronary artery disease. Purpose: To compare DSE volume and positivity rates between 2019 and 2020 time periods in a department of a public tertiary hospital. Methods: We retrospectively analysed DSE studies performed in our department in 2020 including the peak of covid-19 restrictions and compared the data to the 2019. Results: Volume of DSE studies decreased from 1516 in 2019 to 996 in 2020 (-34.3%). The study volume reduction was greater in April (-93.7%) and May (-54.5%) when the covid-19 restrictions were at the peak. Great decreases were also recorded in November (-46.8%) and December (-53.5%) when the second wave of covid-19 disease emerged. Conversely, small increases were recorded in September (7.1%) and October (10.6%) (figure 1). Regarding positivity rates, a statistically non-significant increase was recorded (33.6% vs 34.2% in 2019 and 2020 respectively, p = 0.73). Interestingly a statistically significant increase in positivity levels was recorded during the period March to May 2020 compared to the same period of 2019 (44.7% vs 36.9%, p = 0.029). On the contrary, positivity rates were decreased at the period September to December (27.1% vs 34.2%, p = 0.019) (figure 2). Conclusions: Volume of DSE studies was significantly reduced in 2020 when compared to 2019 during respective peaks of the pandemic and the accompanying restriction measures. Positivity rates were higher during the first pandemic wave, possibly due to decreased hospital attendance of mildly symptomatic patients in combination with stricter admission criteria at the emergency department. Lower positivity rates during the second pandemic wave possibly reflect an adjustment of both healthcare systems and patients to the new conditions imposed by the covid-19 pandemic.

Urology residency training in Greece. Results from the first national resident survey. / Formación de la residencia de Urología en Grecia. Resultados de la primera encuesta nacional.

BACKGROUND AND OBJECTIVES: This is the first national survey assessing Greek Urology residency programs. The main objective of this study is to assess the level of confidence and perception of Greek Urology residents regarding their educational program and detect areas of improvement. MATERIAL AND METHODS: A 51-question survey was developed via an electronic platform and answered by 91 out of 104 Greek residents from March 2019 until May 2019. Fisher's exact test, chi-squared test and Kruskal-Wallis test were used with statistical significance set at p=.05. RESULTS: The median overall satisfaction regarding surgical training was 6/10 regardless of working schedule, working in a University Department, PGY or number of residents in clinic. Most residents have not performed any scrotal ultrasound or pressure-flow-studies; however, they are more familiar with KUB ultrasound. Double-J stent insertion and cystoscopy were common procedures for residents. Bureaucracy was reported as a major issue by 70.4% of residents. ESWL has not been performed by 80.2% of residents, 58.2% residents performed less than 10 ureteroscopies, and only the last year trainees performed more than 10 TURBT and TURP. Most residents mentioned to rarely perform basic steps in many open or laparoscopic urological procedures. Surprisingly, 59.3% of residents have not published any study in peer-reviewed journals. Regarding satisfaction, 44% rarely feel satisfied at work and 59.3% sometimes suffer from burnout. Response rate reached 87.5%. CONCLUSIONS: Considering the results from this survey, regulatory authorities should join forces to establish a structured curriculum of clinical, surgical and research training in Urology across Europe.