Immunotherapy for urothelial carcinoma: Metastatic disease and beyond

For advanced and metastatic urothelial carcinomas (UCs), platinum (preferably cisplatin)‐based chemotherapy has been the standard treatment for many years. However, many patients are ineligible for cisplatin‐based chemotherapy because of poor performance status and/or other age‐related conditions. At the other end of the spectrum, patients with localized non‐muscle–invasive bladder cancer who are unresponsive to intravesical Bacillus Calmette‐Guérin (BCG) treatment often face radical cystectomy as the only option. In recent years, the application of immunotherapy in the form of immune‐checkpoint inhibitors has provided viable alternatives in the second‐line postplatinum and first‐line cisplatin‐ineligible settings. Recent and ongoing clinical trials are also assessing the safety and efficacy of immunotherapy for neoadjuvant and adjuvant uses before/after cystectomy, for BCG‐unresponsive cases, and for combination treatments that include the newer indoleamine 2,3‐dioxygenase‐1 inhibitors and/or BCG. This review summarizes recent developments in immunotherapy for UCs.     

Transthyretin cardiac amyloidosis: A treatable form of heart failure with a preserved ejection fraction

Cardiac amyloidosis (CA) is considered a rare disease with poor prognosis and limited therapeutic options. However, non-biopsy diagnostic modalities as well as emerging therapies are challenging this long-held belief. Radionuclide bone scintigraphy is increasingly being used in the diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CA). As such, it is expected that the number of patients diagnosed with ATTR-CA will continue to rise. Emerging therapies decrease the progressive morbidity and mortality associated with ATTR-CA. The importance of early recognition of ATTR-CA is imperative as prompt initiation of these novel agents is essential to maximize their therapeutic potential. Herein, we outline the current approach to diagnosis of ATTR-CA and review the therapeutic management of the disease.     

Gambling and Problem Gambling in Canada in 2018: Prevalence and Changes Since 2002

Objective:The purpose of this study was to provide an updated profile of gambling and problem gambling in Canada and to examine how the rates and pattern of participation compare to 2002.Method:An assessment of gambling and problem gambling was included in the 2018 Canadian Community Health Survey and administered to 24,982 individuals aged 15 and older. The present analyses selected for adults (18+).Results:A total of 66.2% of people reported engaging in some type of gambling in 2018, primarily lottery and/or raffle tickets, the only type in which the majority of Canadians participate. There are some significant interprovincial differences, with perhaps the most important one being the higher rate of electronic gambling machine (EGM) participation in Manitoba and Saskatchewan. The overall pattern of gambling in 2018 is very similar to 2002, although participation is generally much lower in 2018, particularly for EGMs and bingo. Only 0.6% of the population were identified as problem gamblers in 2018, with an additional 2.7% being at-risk gamblers. There is no significant interprovincial variation in problem gambling rates. The interprovincial pattern of problem gambling in 2018 is also very similar to what was found in 2002 with the main difference being a 45% decrease in the overall prevalence of problem gambling.Conclusions:Gambling and problem gambling have both decreased in Canada from 2002 to 2018 although the provincial patterns are quite similar between the 2 time periods. Several mechanisms have likely collectively contributed to these declines. Decreases have also been reported in several other Western countries in recent years and have occurred despite the expansion of legal gambling opportunities, suggesting a degree of inoculation or adaptation in large parts of the population.     

Does a high Mandard score really define a poor response to chemotherapy in oesophageal adenocarcinoma?

Background A high Mandard score implies a non-response to chemotherapy in oesophageal adenocarcinoma. However, some patients exhibit tumour volume reduction and a nodal response despite a high score. This study examines survival and recurrence patterns in these patients.Methods Clinicopathological factors were analysed using multivariable Cox regression assessing time to death and recurrence. Computed tomography-estimated tumour volume change was examined in a subgroup of consecutive patients.Results Five hundred and fifty-five patients were included. Median survival was 55 months (Mandard 1–3) and 21 months (Mandard 4 and 5). In the Mandard 4 and 5 group (332 patients), comparison between complete nodal responders and persistent nodal disease showed improved survival (90 vs 18 months), recurrence rates (locoregional 14.75 vs 28.74%, systemic 24.59 vs 48.42%) and circumferential resection margin positivity (22.95 vs 68.11%). Complete nodal response independently predicted improved survival (hazard ratio 0.34 (0.16–0.74). Post-chemotherapy tumour volume reduction was greater in patients with a complete nodal response (−16.3 vs −7.7 cm³, p = 0.033) with no significant difference between Mandard groups.Conclusion Patients with a complete nodal response to chemotherapy have significantly improved outcomes despite a poor Mandard score. High Mandard score does not correspond with a non-response to chemotherapy in all cases and patients with nodal downstaging may still benefit from adjuvant chemotherapy.Subject terms: Oesophageal cancer, Surgical oncology     

Humans and machines: Moving towards a more symbiotic approach to learning clinical reasoning

Abstract

Artificial intelligence is a growing phenomenon that is driving major changes to how we deliver healthcare. One of its most significant and challenging contributions is likely to be in diagnosis. Artificial intelligence is challenging the physician’s exclusive role in diagnosis and in some areas, its diagnostic accuracy exceeds that of humans. We argue that we urgently need to consider how we will incorporate AI into our teaching of clinical reasoning in the undergraduate curriculum; students need to successfully navigate the benefits and potential issues of new and developing approaches to AI in clinical diagnosis. We offer a pedagogical framework for this challenging change to our curriculum.