Interactions between human microbiome,liver diseases,and immunosuppression after liver transplant

In liver transplant patients, solid tumors and post-transplant lymphoproliferative disorders have emerged as significant long-term mortality causes. In addition, it is assumed that de novo malignancy after liver transplantation (LT) is the second-leading cause of death after cardiovascular complications. Well-established risk factors for post-transplant lymphoproliferative disorders and solid tumors are calcineurin inhibitors, tacrolimus, and cyclosporine, the cornerstones of all immunosuppressive therapies used after LT. The loss of immunocompetence facilitated by the host immune system due to prolonged immunosuppressive therapy leads to cancer development, including LT patients. Furthermore, various mechanisms such as bacterial dysbiosis, activation through microbe-associated molecular patterns, leaky gut, and bacterial metabolites can drive cancer-promoting liver inflammation, fibrosis, and genotoxicity. Therefore, changes in human microbiota composition may contribute further to de novo carcinogenesis associated with the severe immunosuppression after LT.     

Predictors of survival following surgical resection of limited-stage small cell lung cancer

BackgroundAdjuvant chemotherapy, postoperative radiation (PORT), and prophylactic cranial irradiation (PCI) have been individually examined in limited-stage small cell lung cancer (SCLC). There is a paucity of data on the effectiveness of each adjuvant treatment modality when used in combination after surgical resection of SCLC.MethodsData were collected from 5 cancer centers on all patients with limited-stage SCLC who underwent surgical resection between 1986 and 2019. Univariate and multivariable models were conducted to identify predictors of long-term outcomes, focusing on freedom from recurrence and survival benefit of adjuvant chemotherapy, PORT, and PCI.ResultsA total of 164 patients were analyzed. Multivariable Cox regression analysis did not identify any adjuvant therapies to significantly influence recurrence in this cohort. Specifically, PORT was not associated with a significant influence on locoregional recurrence and PCI was not significantly associated with intracranial outcomes. Adjuvant chemotherapy improved survival in all stage I through III disease (hazard ratio, 0.49; 95% confidence interval, 0.29-0.81; P = .005) and even in pathologically node negative patients (hazard ratio, 0.49; 95% confidence interval, 0.27-0.91; P = .024). Although PCI was found to improve survival in univariate analysis, it was not significant in a multivariable model. PORT was not found to affect survival on either univariate or multivariable analysis.ConclusionsThis is among the largest multi-institutional studies on surgically resected limited-stage SCLC. Our results highlight survival benefit of adjuvant chemotherapy, but did not identify a statistically significant influence from mediastinal PORT or PCI in our cohort. Larger prospective studies are needed to determine the benefit of PORT or PCI in a surgically resected limited-stage SCLC population.     

Variabilidad del uso intraoperatorio de cristaloides y asociación con los resultados postoperatorios: análisis post hoc de dos estudios prospectivos y multicéntricos de cohortes

BackgroundThe optimal regimen for intravenous administration of intraoperative fluids remains unclear. Our goal was to analyze intraoperative crystalloid volume administration practices and their association with postoperative outcomes.MethodsWe extracted clinical data from two multicenter observational studies including adult patients undergoing colorectal surgery and total hip (THA) and knee arthroplasty (TKA). We analyzed the distribution of intraoperative fluid administration. Regression was performed using a general linear model to determine factors predictive of fluid administration. Patient outcomes and intraoperative crystalloid utilization were summarized for each surgical cohort. Regression models were developed to evaluate associations of high or low intraoperative crystalloid with the likelihood of increased postoperative complications, mainly acute kidney injury (AKI) and hospital length of stay (LOS).Results7,580 patients were included. The average adjusted intraoperative crystalloid infusion rate across all surgeries was to 7.9 (SD 4) mL/kg/h. The regression model strongly favored the type of surgery over other patient predictors. We found that high fluid volume was associated with 40% greater odds ratio (OR 1.40; 95% confidence interval1.01-1.95, p = 0.044) of postoperative complications in patients undergoing THA, while we found no associations for the other types of surgeries, AKI and LOSConclusionsA wide variability was observed in intraoperative crystalloid volume administration; however, this did not affect postoperative outcomes.     

Improving Lesbian,Gay, Bisexual,Transgender, Queer and Two-Spirit Content in a Radiation Therapy Undergraduate Curriculum

Lesbian, gay, bisexual, transgender, queer and two-spirit plus (LGBTQ2S+) people have distinct healthcare needs that may be unaddressed in many undergraduate healthcare curricula. The Radiation Therapy Program (RADTH) at the University of Alberta underwent a review of the three-year didactic curriculum using an online survey. The survey sought to ascertain if, where and how topics related to LGBTQ2S + healthcare are taught. Results indicated that out of 10 RADTH program faculty respondents, three teach related topics. The total time dedicated within the three-year curriculum was approximately three and a half hours. Other findings showed that faculty are interested in receiving more education in this area and would favour discussions about how to incorporate these themes into appropriate courses. This preliminary investigation demonstrated that there has been some initial work in this area, but there is more to be done.     

术中目标导向液体治疗在腹膜后巨大恶性肿瘤切除术患儿中的应用

目的:探讨基于脉压变异度（PPV）的目标导向液体治疗（GDFT）在腹膜后巨大恶性肿瘤切除术患儿中的应用。方法:择期行腹膜后巨大恶性肿瘤切除术患儿64例，年龄0.5~3岁，ASA Ⅱ-Ⅲ级。随机将患儿分为目标导向液体治疗组（G组）和常规液体治疗组（C组），每组32例。G组以PPV为指导，根据GDFT方案进行液体管理，C组采用常规液体管理。记录手术开始（T1）、手术开始后1 h（T2）、手术结束（T3）的MAP、CVP、PPV、Lac值、TNF-α、IL-6浓度。记录术中输注晶体液量、胶体液量、液体总量、出血量、尿量、手术时间、多巴胺使用率以及排气时间、术后住院时间和恶心呕吐发生率。结果:G组输注晶体液量显著少于C组（P＜0.05），而输注胶体液量显著多于C组（P＜0.05）。两组术中输注液体总量、出血量、尿量与多巴胺使用率方面差异无统计学意义。T2、T3时刻，G组PPV、TNF-α、IL-6显著低于C组（P＜0.05），而两组间MAP、CVP、Lac在各时点差异无统计学意义。G组术后排气时间明显短于C组（P＜0.05），而在术后恶心呕吐发生率和住院时间方面两组差异无统计学意义。结论:PPV指导的GDFT可以应用于腹膜后巨大恶性肿瘤切除术患儿，能维持其血流动力学稳定，减少炎症因子IL-6、TNF-α释放，促进胃肠功能恢复，但对术后转归无明显影响。     

Neoadjuvant Therapy for Locally Advanced Rectal Cancer: Recent Advances and Ongoing Challenges

Locally advanced rectal cancer has a rising global incidence. Over the last 4 decades, advances first in surgery and later in radiotherapy and chemoradiotherapy have improved outcomes, particularly with regard to local recurrence. Unfortunately, distant metastases remain a significant problem. In clinical trials of patients with stage II and III disease, distant relapse occurs in 25% to 30% of patients regardless of the treatment approach. Recent phase 3 trials have therefore focused on intensification of systemic therapy for localized disease, with an aim of reducing the distant relapse rate. Early results of trials of total neoadjuvant therapy with combination systemic therapy provided in the neoadjuvant setting are promising; for the first time, a significant improvement in the rate of distant relapse has been noted. Longer-term follow-up is eagerly awaited. On the other hand, trimodal therapy with chemotherapy, radiotherapy, and surgery is toxic. Several trials are currently assessing the feasibility of a watch-and-wait approach, omitting surgery in those with complete response to neoadjuvant treatment, in an attempt to reduce the burden of treatment on patients. The future for rectal cancer patients is likely to be highly personalized, with more intense approaches for high-risk patients and omission of unnecessary therapy for those whose disease responds well to initial treatment. Biomarkers such as circulating tumor DNA will help to more accurately stratify patients into risk groups. Improvements in survival and quality of life are expected as the results of ongoing research become available throughout the next decade.