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European Urology Sep 2020There is a critical need for effective bladder-sparing therapies for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). Owing to...
CONTEXT
There is a critical need for effective bladder-sparing therapies for bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). Owing to the current lack of effective agents that can be used as a control, the US Food and Drug Administration began to accept single-arm trials for patients with carcinoma in situ (CIS), using complete response rate (CRR) and duration of response as the primary endpoints to support marketing applications. Despite the ensuing growth of clinical trials in this space, no consensus exists on a clinically relevant benchmark for CRR.
OBJECTIVE
To elucidate the CRR and recurrence-free rate (RFR) using bladder-sparing agents after BCG failure in order to provide a frame of reference for future clinical trial results.
EVIDENCE ACQUISITION
We performed a systematic review of clinical trials utilizing bladder-sparing therapeutics for NMIBC recurring after intravesical BCG (PROSPERO CRD42019130553). The search was performed in MEDLINE, EMBASE, and Cochrane Library. Relevant studies identified from bibliography search and conference abstracts were searched to complement the systematic review. A total of 42 studies utilizing 24 treatment options and consisting of 2254 patients were included for final analysis.
EVIDENCE SYNTHESIS
Median CRRs in the treatment of CIS-containing tumors were 26% at 6 mo, 17% at 12 mo, and 8% at 24 mo after treatment. In comparison, median RFRs in the papillary-only studies were 67% at 6 mo, 44% at 12 mo, and 10% at 24 mo. Specifically in the BCG-unresponsive population, 6- and 12-mo CRRs in CIS-containing patients treated with Mycobacterium phlei cell wall-nucleic acid complex were 45% and 27%, respectively, and the median 6-, 12-, and 24-mo disease-free rates in the other studies were 43%, 35%, and 18%, respectively. The median progression-free rate was 91%: 95% in the CIS-containing studies and 89% in studies restricted to papillary-only recurrences. Toxicities of intravesical agents were generally mild, with very few dose limiting toxicities.
CONCLUSIONS
We demonstrate that, to date, bladder-sparing therapies achieved modest efficacy in patients with NMIBC after BCG. Results from the current study will serve as a frame of reference for emerging trial results in the BCG-unresponsive space.
PATIENT SUMMARY
In this study, we found that bladder-sparing therapies achieved modest efficacy in patients with non-muscle-invasive bladder cancer after bacillus Calmette-Guérin (BCG). These results will serve to inform future clinical trial results for salvage agents used to treat BCG-unresponsive bladder cancer.
Topics: Adjuvants, Immunologic; Administration, Intravesical; BCG Vaccine; Carcinoma in Situ; Humans; Neoplasm Invasiveness; Organ Sparing Treatments; Treatment Outcome; Urinary Bladder Neoplasms
PubMed: 32143924
DOI: 10.1016/j.eururo.2020.02.012 -
Annals of Cardiothoracic Surgery May 2022Mechanical complications following acute myocardial infarction (AMI), though rare, are associated with significant morbidity and mortality. Surgical management remains a...
BACKGROUND
Mechanical complications following acute myocardial infarction (AMI), though rare, are associated with significant morbidity and mortality. Surgical management remains a mainstay of therapy for these complications. The purpose of this review is to evaluate long-term outcomes data of surgical management for postinfarction free wall rupture, ventricular septal defect, papillary muscle rupture, and pseudoaneurysm.
METHODS
An electronic literature search was performed to identify original studies reporting long-term outcomes data of surgical management of one of the four mechanical complications following AMI. Studies were considered to have long-term outcomes if they at minimum included survival or mortality data up to one year.
RESULTS
A total of 285 studies were identified from the literature search. Of these, 29 studies with long-term survival data on surgically managed mechanical complications of AMI are included in the review. The majority of these are retrospective cohort studies or single-center case series. Five studies are included on free wall rupture, 18 on ventricular septal defect, 4 on papillary muscle rupture, and 2 on pseudoaneurysm. Detailed results are tabulated according to complication.
CONCLUSIONS
Long-term surgical outcomes of postinfarction mechanical complications remain understudied. Outcomes for ventricular septal defect repair are better represented in the literature than are outcomes for other mechanical complications, though available studies are still limited by small sample sizes and retrospective design. Further research is warranted, particularly for outcomes of acute pseudoaneurysm repair.
PubMed: 35733723
DOI: 10.21037/acs-2021-ami-20 -
General Thoracic and Cardiovascular... Feb 2021The current treatment of ischemic functional mitral regurgitation (FMR) remains debated due to differences in inclusion criteria of randomized studies and baseline...
OBJECTIVE
The current treatment of ischemic functional mitral regurgitation (FMR) remains debated due to differences in inclusion criteria of randomized studies and baseline characteristics. Also, the role of left ventricular pathophysiology and the role of subvalvular apparatus have not been thoroughly investigated in recent literature.
METHODS
A literature search was performed from PubMed inception to June 2020.
RESULTS
Novel concepts of pathophysiology, such as the proportionate/disproportionate conceptual framework, the role of papillary muscles and left ventricular dysfunction, the impact of myocardial ischemia and revascularization, left ventricular remodeling, and the effect of restrictive annuloplasty or subvalvular procedures have been reviewed.
CONCLUSIONS
The clinical benefits associated with the use of MitraClip is more evident in patients with disproportionate FMR with greater and sustained left ventricular reverse remodeling. Importantly, in the absence of myocardial revascularization, expansion of myocardial scar tissue and non-perfused areas of ischemic myocardium occur with time, and this impact on outcomes with a longer follow-up period cannot be quantified. In advanced phases of FMR, neither mitral ring annuloplasty nor percutaneous therapies could significantly modify the established pathoanatomic alterations.
Topics: Humans; Mitral Valve; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Myocardial Ischemia; Papillary Muscles; Treatment Outcome; Ventricular Remodeling
PubMed: 33400198
DOI: 10.1007/s11748-020-01562-5 -
Journal of Cardiovascular Medicine... Oct 2019: Traumatic mitral valve regurgitation is a rare and often insidious condition. Clinical presentation is variable and influenced by the anatomic structures injured; when...
: Traumatic mitral valve regurgitation is a rare and often insidious condition. Clinical presentation is variable and influenced by the anatomic structures injured; when papillary muscles are damaged, the clinical presentation is often acute, whereas, in the case of involvement of other anatomic structures of the valvular apparatus (e.g. chordae tendinae), the onset of symptoms may be delayed (days, weeks, or months). Therefore, diagnosis may be belated because of the heterogeneous clinical presentation. Traumatic mitral valve injury should be excluded in patients admitted to the emergency services with blunt chest trauma, in particular when signs or symptoms of acute heart failure occur. Echocardiography, particularly with the transoesophageal approach, may play a pivotal role in this setting. Herein, we present a case of severe mitral regurgitation because of blunt chest trauma and a systematic review of the literature. We examined 192 described cases, classified according to epidemiology, aetiology, anatomic features, clinical presentation, diagnosis, surgical/clinical management and prognosis.
Topics: Accidents, Occupational; Heart Injuries; Humans; Male; Middle Aged; Mitral Valve; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Recovery of Function; Severity of Illness Index; Treatment Outcome; Wounds, Nonpenetrating
PubMed: 31246700
DOI: 10.2459/JCM.0000000000000809 -
Ontario Health Technology Assessment... 2021Bladder cancer begins in the innermost lining of the bladder wall and, on histological examination, is classified as one of two types: non-muscle-invasive bladder cancer... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Bladder cancer begins in the innermost lining of the bladder wall and, on histological examination, is classified as one of two types: non-muscle-invasive bladder cancer (NMIBC) or muscle-invasive bladder cancer. Transurethral resection of bladder tumour (TURBT) is the standard treatment for people with NMIBC, but the high rate of cancer recurrence after first TURBT is a challenge that physicians and patients face. Tumours seen during follow-up may have been missed or incompletely resected during first TURBT. TURBT is conventionally performed using white light to see the tumours. However, small papillary or flat tumours may be missed with the use of white light alone. With the emergence of new technologies to improve visualization during TURBT, better diagnostic and patient outcomes may be expected. We conducted a health technology assessment of two enhanced visualization methods, both as an adjunct to white light to guide first TURBT for people with suspected NMIBC-hexaminolevulinate hydrochloride (HAL), a solution that is instilled into the bladder to make tumours fluoresce under blue-violet light, and narrow band imaging (NBI), a technology that filters light into wavelengths that can be absorbed by hemoglobin in the tumours, making them appear darker. Our assessment included an evaluation of effectiveness, safety, cost-effectiveness, and the budget impact of publicly funding these new technologies to improve patient outcomes following first TURBT. The use of NBI in diagnostic cystoscopy was out of scope for this health technology assessment.
METHODS
We performed a systematic literature search of the clinical evidence from inception to April 15, 2020. We searched for randomized controlled trials (RCTs) that compared the outcomes of first TURBT with the use of HAL or NBI, both as an adjunct to white light, with the outcomes of first TURBT using white light alone, or studies that made such comparison between HAL and NBI. We conducted pairwise meta-analyses using a fixed effects model where head-to-head comparisons were available. In the absence of any published RCT for comparison between HAL and NBI, we indirectly compared the two technologies through indirect treatment comparison (ITC) analysis. We assessed the risk of bias of each included study using the Cochrane risk-of-bias tool. We assessed the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted a cost-utility analysis with a 15-year time horizon from a public payer perspective. We also analyzed the budget impact of publicly funding HAL and NBI as an adjunct to white light in people undergoing their first TURBT for suspected non-muscle-invasive bladder cancer in Ontario.
RESULTS
In the clinical evidence review, we identified 8 RCTs that used HAL or NBI as an adjunct to white light during first TURBT. Pairwise meta-analysis of HAL studies showed that HAL-guided TURBT as an adjunct to white light significantly reduces recurrence rate at 12 months compared with TURBT using white light alone (risk ratio 0.70, 95% confidence interval [CI] 0.51-0.95) (GRADE: Moderate). Five-year recurrence-free survival was significantly higher when HAL was used as an adjunct to white light than when white light was used alone (GRADE: Moderate). There was little to no difference in the tumour progression rate (GRADE: Moderate).Meta-analysis of NBI studies did not show a significant difference between NBI-guided TURBT as an adjunct to white light and TURBT using white light alone in reducing the rate of recurrence at 12 months (risk ratio 0.94, 95% CI 0.75-1.19) (GRADE: Moderate). No evidence on the effect on recurrence-free survival or tumour progression rate was identified for NBI-guided TURBT. The indirect estimate from the network analysis showed a trend toward a lower rate of recurrence after HAL-guided TURBT than after NBI-guided TURBT but the difference was not statistically significant (risk ratio 0.76, 95% CI 0.51-1.11) (GRADE: Low). Studies showed that use of HAL or NBI during TURBT was generally safe.The incremental cost-effectiveness ratio of HAL-guided TURBT compared with NBI-guided TURBT, both as an adjunct to white light, is $12,618 per quality-adjusted life-year (QALY) gained. Compared with TURBT using white light alone and using adjunct NBI, the probability of HAL-guided TURBT being cost-effective is 69.1% at a willingness-to-pay value of $50,000 per QALY gained and 74.6% at a willingness-to-pay of $100,000 per QALY gained. The annual budget impact of publicly funding HAL-guided TURBT in Ontario over the next 5 years ranges from an additional $0.6 million in year 1 to $2.5 million in year 5.
CONCLUSIONS
First TURBT guided by HAL as an adjunct to white light likely reduces the rate of recurrence at 12 months and increases 5-year recurrence-free survival when compared with first TURBT using white light alone. There is likely little to no difference in the tumour progression rate. First TURBT guided by NBI as an adjunct to white light likely results in little to no difference in the rate of recurrence at 12 months when compared with first TURBT using white light alone. Based on an indirect comparison, there may be little to no difference in cancer recurrence rate between HAL-guided and NBI-guided first TURBT. Use of HAL or NBI during first TURBT is generally safe. For people undergoing their first TURBT for suspected non-muscle-invasive bladder cancer, using HAL as an adjunct to white light is likely to be cost-effective compared with using white light alone or with using NBI as an adjunct to white light. We estimate that publicly funding HAL as an adjunct to white light to guide first TURBT for people in Ontario with suspected NMIBC would result in additional costs of between $0.6 million and $2.5 million per year over the next 5 years.
Topics: Cost-Benefit Analysis; Humans; Neoplasm Recurrence, Local; Quality-Adjusted Life Years; Technology Assessment, Biomedical; Urinary Bladder Neoplasms
PubMed: 34484486
DOI: No ID Found