Salvage therapy for BCG failure with intravesical sequential gemcitabine and docetaxel in patients with recurrent NMIBC.

INTRODUCTION: Bacillus Calmette-Guérin (BCG) failure occurs in approximately 40% of patients with non-muscle-invasive bladder cancer (NMIBC) within two years. We describe our institutional experience with sequential intravesical gemcitabine and docetaxel (gem/doce) as salvage therapy post-BCG failure in patients who were not candidates for or declined radical cystectomy (RC). METHODS: We retrospectively reviewed NMIBC patients with BCG failure who received gem/doce from April 2019 through October 2022 at the CHU de Québec-Université Laval. Patients received at least five weekly intravesical instillations according to published protocols. Patients who responded to gem/doce had maintenance instillations monthly for up to two years. Primary outcome was progression-free survival (PFS). Secondary outcomes included recurrence-free survival (RFS), cystectomy-free survival (CFS), cancer-specific survival (CSS), overall survival (OS), and treatment adverse events. Survival probabilities were estimated using the Kaplan-Meier method from the first gem/doce instillation. RESULTS: Thirty-five patients with a median age of 78 years old were included in the study. The median followup time was 21 months (interquartile range 10-29). More than 25% of patients received two or more prior BCG induction treatments. Overall and MIBC PFS estimates at one year were 85% and 88%, and at two years, 60% and 70%, respectively. Adverse events occurred in 37% of the patients, but only two patients didn't complete the treatment due to intolerance. Three patients underwent RC due to cancer progression. OS was 94% at two years. CONCLUSIONS: With 60% of PFS at two years, gem/doce appears to be a safe and well-tolerated option for BCG failure patients. Further studies are needed to justify widespread use.

Changes in arterial stiffness indices during a single haemodialysis session in end-stage renal disease population: a systematic review and meta-analysis protocol.

INTRODUCTION: Patients with end-stage renal disease are at higher risk of cardiovascular morbidity and mortality, a risk mediated in part by increased aortic stiffness. Arterial stiffness is assessed at different anatomical locations (central elastic or peripheral muscular arteries) using a variety of mechanical biomarkers. However, little is known on the robustness of each of these mechanical biomarkers following a haemodynamic stress caused by a single haemodialysis (HD) session. METHODS AND ANALYSIS: A systematic review has been designed and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. A targeted search strategy applicable in key databases (PubMed, Embase, the Cochrane Library, Web of Science and grey literature) is constructed to search articles and reviews from inception to 16 October 2020. Only articles of studies conducted with adults under chronic HD for kidney failure, with repeated measures of arterial stiffness metrics (pulse wave velocity, Augmentation Index, arterial distensibility or stiffness) following a before-and-after design surrounding a HD session will be selected. The screening process, data extraction and assessment of risk bias will be done by two independent pairs of reviewers. Meta-analysis will enable adjustments for potential confounders and subgroup analyses will be performed to discriminate changes in arterial stiffness metrics from elastic, muscular or global arterial territories. ETHICS AND DISSEMINATION: This study does not require ethical approval. Findings will be submitted for publication to relevant peer-reviewed journals and will be presented at profession-specific conferences. PROSPERO REGISTRATION NUMBER: CRD42020213946.

Radial-digital pulse wave velocity: a noninvasive method for assessing stiffness of small conduit arteries.

Pulse wave velocity (PWV) is used to evaluate regional stiffness of large and medium-sized arteries. Here, we examine the feasibility and reliability of radial-digital PWV (RD-PWV) as a measure of regional stiffness of small conduit arteries and its response to changes in hydrostatic pressure. In 29 healthy subjects, we used Complior Analyse piezoelectric probes to record arterial pulse wave at the radial artery and the tip of the index. We determined transit time by second-derivative and intersecting tangents using the device-embedded algorithms and in-house MATLAB-based analyses of only reliable waves and by numerical simulation using a one-dimensional (1-D) arterial tree model coupled with a heart model. Second-derivative RD-PWV was 4.68 ± 1.18, 4.69 ± 1.21, and 4.32 ± 1.19 m/s for device-embedded, MATLAB-based, and numerical simulation analyses, respectively. Intersecting-tangent RD-PWV was 4.73 ± 1.20, 4.45 ± 1.08, and 4.50 ± 0.84 m/s for device-embedded, MATLAB-based, and numerical simulation analyses, respectively. Intersession coefficients of variation were 7.0% ± 4.9% and 3.2% ± 1.9% (P = 0.04) for device-embedded and MATLAB-based second-derivative algorithms, respectively. In 15 subjects, we examined the response of RD-PWV to changes in local hydrostatic pressure by vertical displacement of the hand. For an increase of 10 mmHg in local hydrostatic pressure, RD-PWV increased by 0.28 m/s (95% confidence interval: 0.16-0.40; P < 0.001). This study shows that RD-PWV can be used for the noninvasive assessment of regional stiffness of small conduit arteries. This finding allows for an integrated approach for assessing arterial stiffness gradient from the aorta to medium-sized arteries and now to small conduit arteries.NEW & NOTEWORTHY The interaction between the stiffness of various arterial segments is important in understanding the behavior of pressure and flow waves along the arterial tree. In this article, we provide a novel and noninvasive method of assessing the regional stiffness of small conduit arteries using the same piezoelectric sensors used for determination of pulse wave velocity over large- and medium-sized arteries. This development allows for an integrated approach for studying arterial stiffness gradient.

Modulation of Arterial Stiffness Gradient by Acute Administration of Nitroglycerin.

Background: Physiologically, the aorta is less stiff than peripheral conductive arteries, creating an arterial stiffness gradient, protecting microcirculation from high pulsatile pressure. However, the pharmacological manipulation of arterial stiffness gradient has not been thoroughly investigated. We hypothesized that acute administration of nitroglycerin (NTG) may alter the arterial stiffness gradient through a more significant effect on the regional stiffness of medium-sized muscular arteries, as measured by pulse wave velocity (PWV). The aim of this study was to examine the differential impact of NTG on regional stiffness, and arterial stiffness gradient as measured by the aortic-brachial PWV ratio (AB-PWV ratio) and aortic-femoral PWV ratio (AF-PWV ratio). Methods: In 93 subjects (age: 61 years, men: 67%, chronic kidney disease [CKD]: 41%), aortic, brachial, and femoral stiffnesses were determined by cf-PWV, carotid-radial (cr-PWV), and femoral-dorsalis pedis artery (fp-PWV) PWVs, respectively. The measurements were repeated 5 min after the sublingual administration of NTG (0.4 mg). The AB-PWV and AF-PWV ratios were obtained by dividing cf-PWV by cr-PWV or fp-PWV, respectively. The central pulse wave profile was determined by radial artery tonometry through the generalized transfer function. Results: At baseline, cf-PWV, cr-PWV, and fp-PWV were 12.12 ± 3.36, 9.51 ± 1.81, and 9.71 ± 1.89 m/s, respectively. After the administration of NTG, there was a significant reduction in cr-PWV of 0.86 ± 1.27 m/s (p < 0.001) and fp-PWV of 1.12 ± 1.74 m/s (p < 0.001), without any significant changes in cf-PWV (p = 0.928), leading to a significant increase in the AB-PWV ratio (1.30 ± 0.39 vs. 1.42 ± 0.46; p = 0.001) and AF-PWV ratio (1.38 ± 0.47 vs. 1.56 ± 0.53; p = 0.001). There was a significant correlation between changes in the AF-PWV ratio and changes in the timing of wave reflection (r = 0.289; p = 0.042) and the amplitude of the heart rate-adjusted augmented pressure (r = - 0.467; p < 0.001). Conclusion: This study shows that acute administration of NTG reduces PWV of muscular arteries (brachial and femoral) without modifying aortic PWV. This results in an unfavorable profile of AB-PWV and AF-PWV ratios, which could lead to higher pulse pressure transmission into the microcirculation.

Enhanced recovery pathways in thoracic surgery: the Quebec experience.

BACKGROUND: Canada has a universal public health system where all resources must be allocated to optimize cost-effectiveness. Rapid diagnostic assessment programs (DAPs) and enhanced recovery protocols (ERPs) may improve timeliness of care and postoperative outcomes and thus reduce costs. The use of DAPs and ERPs in lung cancer patients who undergo lobectomy via video-assisted thoracoscopic surgery (VATS) is still controversial. This study measured the time between preoperative workup and treatment with a DAP and evaluated the impact of an ERP postoperatively in patients with early-stage non-small cell lung cancer (NSCLC) who received a VATS lobectomy. METHODS: We conducted a retrospective review of patients who underwent minimally invasive lobectomy for the primary treatment of lung cancer from January 2014 through May 2017 at our institution. Timelines of care were measured. Postoperatively, the duration of chest tube drainage, length of hospital stay, and incidence of complications were noted. RESULTS: During the study period, 646 patients underwent VATS lobectomy for stage I or II NSCLC; of these, 384 (59%) were assessed within the DAP. Using the DAP, the median time between the patient's first clinic visit and referral to surgery was 30.0 days [interquartile range (IQR), 21.0-40.0 days), and the median time between surgical consult and treatment was 29.0 days (IQR, 15.0-47.5 days). With the ERP, the median duration of chest drainage was 3.0 days (IQR, 2.0-6.0 days), and median hospital stay was 4.0 days (IQR, 3.0-7.0 days). CONCLUSIONS: DAPs and ERPs have promising roles in thoracic surgical practice. A rapid DAP can expedite the care trajectory of patients with lung cancer and has allowed our institution to adhere to governmental standards for the management of lung cancer. ERPs are feasible to establish and can effectively improve clinical outcomes.