Survival and Outcomes of Newly Diagnosed Multiple Myeloma Patients Stratified by Transplant Status 2007-2018: Retrospective Analysis from the Canadian Myeloma Research Group Database

BackgroundConsiderable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization.MethodsThe Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018.ResultsA total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment.ConclusionWe present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.     

Time-varying association of second primary malignancy and long-term survival outcomes in patients with head and neck cancer

A high risk of developing second primary malignancy (SPM) has been reported among head and neck cancer patients. Here, we aimed to statistically quantify the impact of SPM development on the survival of head and neck cancer patients. Our study was conducted using the Surveillance, Epidemiology and End Results database to collect the data of 48 316 patients who received curative surgical resection for initial primary head and neck squamous cell carcinoma (IP-HNSCC) in 1975 to 2019. SPM diagnosis was treated as a time-varying covariate and multivariable Cox regression analysis was conducted to estimate the association between SPM development and survival, overall or by the subsite of IP-HNSCC. Of the included patients, 11 238 patients (23.3%) developed SPM during the follow-up period. A significant reduction in survival was observed among patients with SPM (hazard ratio [HR] for overall survival, 3.30; 95% confidence interval [CI]: 3.20-3.41). The impact of SPM development on reduced survival was more significant in patients with localized IP-HNSCC vs regional IP-HNSCC (HR_OS, 3.41; 95% CI: 3.24-3.6 vs HR_OS, 3.18; 95% CI: 3.05-3.31; P for interaction <.001). The survival impact of SPM development was more evident in younger patients than in older patients. SPM in lung and bronchus was associated with the most pronounced reduction in survival, overall and across all subsites of HNSCC. Our results indicated that SPM development led to a significant reduction in survival. A greater survival benefit may be achieved through intensive surveillance for SPM in lung and bronchus targeting younger patients and those with localized HNSCC.     

Oxygen delivery-guided perfusion for the prevention of acute kidney injury: A randomized controlled trial

ObjectivesThe reduction of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass surgery using an oxygen delivery-guided perfusion strategy (oxygen delivery strategy) for cardiopulmonary bypass management compared with a fixed flow perfusion (conventional strategy) remains controversial. The purpose of this study was to determine whether a oxygen delivery strategy would reduce the incidence of postoperative acute kidney injury in patients undergoing cardiopulmonary bypass surgery.MethodsWe randomly enrolled 300 patients undergoing cardiopulmonary bypass surgery. Patients were randomly assigned to a oxygen delivery strategy (maintaining a oxygen delivery index value >300 mL/min/m² through pump flow adjustments during cardiopulmonary bypass) or a conventional strategy (a target pump flow was determined on the basis of the body surface area). The primary end point was the development of acute kidney injury. Secondary end points were the red blood cell transfusion rate and number of red blood cell units, intubation time, postoperative length of stay in the intensive care unit and the hospital, predischarge estimated glomerular filtration rate, and hospital mortality.ResultsAcute kidney injury occurred in 20 patients (14.6%) receiving the oxygen delivery strategy and in 42 patients (30.4%) receiving the conventional strategy (relative risk, 0.48; 95% confidence interval, 0.30-0.77; P = .002). The secondary end points were not significantly different between strategies. In a prespecified subgroup analysis of patients who had nadir hematocrit less than 23% or body surface area less than 1.40 m², the oxygen delivery strategy seemed to be superior to the conventional strategy and the existence of quantitative interactions was suggested.ConclusionsAn oxygen delivery strategy for cardiopulmonary bypass management was superior to a conventional strategy with respect to preventing the development of acute kidney injury.     

胸段食管鳞癌术后复发模式及术后放疗靶区的研究北大核心

目的:研究胸段食管鳞癌术后复发模式,为术后放疗靶区勾画提供参考。方法:回顾分析我院2012年7月至2017年5月收治术后复发的81例胸段食管鳞癌患者的临床资料,参照AJCC第八版食管癌分期,将第1-8M站定义为上中纵隔淋巴结区,8Lo、9、15站定义为下纵隔淋巴结区,16-20站定义为上腹部淋巴结区。标记患者的复发部位,并分析局部复发、区域复发和远处转移的模式。结果:中位复发时间为12个月(2~103个月)。6例(7.4%)患者发生单纯局部复发,64例(79.0%)患者发生区域复发,11例(13.6%)患者发生远处转移。区域淋巴结复发中最高危的复发区域为上中纵隔淋巴引流区,此区域包含了82.8%的复发淋巴结,其次为上腹部淋巴结引流区(13.6%)。11例患者发生上腹部淋巴结复发,其中10(90.9%)例为胸下段,7例(63.6%)患者术后分期≥Ⅲ_(b)期。结论:胸段食管鳞癌术后复发模式以区域淋巴结复发为主,上中纵隔淋巴引流区为最高危复发区域,术后放疗靶区应重点包含。对于术后分期较晚的胸下段食管鳞癌,上腹部淋巴结引流区可能需要涵盖在放疗靶区内。吻合口、瘤床和下纵隔复发风险低,可不必常规涵盖在放疗靶区内。     

Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.     

Regeneration in anamniotes was replaced by regengrow and scarring in amniotes after land colonization and the evolution of terrestrial biological cycles

An evolutionary hypothesis explaining failure of regeneration among vertebrates is presented. Regeneration derives from postembryonic processes present during the life cycles of fish and amphibians that include larval and metamorphic phases with broad organ reorganizations. Developmental programs imprinted in their genomes are re-utilized with variations also in adults for regeneration. When vertebrates colonized land adopting the amniotic egg, some genes driving larval changes, and metamorphosis were lost and new genes evolved, further limiting regeneration. These included neural inhibitors for maintaining complex nervous systems, behavior and various levels of intelligence, and adaptive immune cells. The latter, that in anamniotes are executioners of metamorphic reorganization, became intolerant to embryonic-oncofetal-antigens impeding organ regeneration, a process that requires de-differentiation of adult cells and/or expansion of stem cells where these early antigens are formed. The evolution of terrestrial lifecycles produced vertebrates with complex bodies but no longer capable to regenerate their organs, mainly repaired by regengrow. Efforts of regenerative medicine to improve healing in humans should determine the diverse developmental pathways evolved between anamniotes and amniotes before attempting genetic manipulations such as the introduction of “anamniote regenerative genes” in amniotes. This operation may determine alteration in amniote developmental programs leading to teratomes, cancer, or death.