The National Burden of Colorectal Cancer in the United States from 1990 to 2019

CRC accounts for approximately a tenth of all cancer cases and deaths in the US. Due to large differences in demographics among the different states, we aim to determine trends in the CRC epidemiology and across different states, age groups, and genders. CRC rates, age-adjusted to the standard US population, were obtained from the GBD 2019 database. Time trends were estimated as annual percentage change (APC). A pairwise comparison was conducted between age- and gender-specific trends using the tests of parallelism and coincidence. Age-specific trends were also assessed in two age subgroups: younger adults aged 15-49 years and older adults aged 50-74 years. We also analyzed the prevalence, incidence, mortality, and DALYs in the US between 1990 and 2019. A total of 5.53 million patients were diagnosed with CRC in the US between 1990 and 2019. Overall, CRC incidence rates have significantly increased in younger adults (11.1 per 100,000 persons) and decreased in older adults (136.8 per 100,000 persons) (AAPC = 1.2 vs. -0.6; AAPC difference = 1.8, p < 0.001). Age-specific trends were neither identical (p < 0.001) nor parallel (p < 0.001), suggesting that CRC incidence rates are different and increasing at a greater rate in younger adults compared to older adults. However, for both men and women (49.4 and 35.2 per 100,000 persons), incidence rates have decreased over the past three decades at the same rate (AAPC = -0.5 vs. -0.5; AAPC difference = 0, p = 0.1). Geographically, the southern states had the highest mortality rates with Mississippi having the highest rate of 20.1 cases per 100,000 population in 2019. Massachusetts, New York, and the District of Colombia had the greatest decreases in mortality over the study period (-42.1%, -41.4%, and -40.9%). Decreased mortality was found in all states except Mississippi, where the mortality of CRC increased over the study period (+1.5%). This research provides crucial insights for policymakers to tailor resource allocation, emphasizing the dynamic nature of CRC burden across states and age groups, ultimately informing targeted strategies for prevention and intervention

Transjugular Intrahepatic Portosystemic Shunt With or Without Gastroesophageal Variceal Embolization for the Prevention of Variceal Rebleeding: A Systematic Review and Meta-Analysis

Background: The role of variceal embolization (VE) during transjugular intrahepatic portosystemic shunt (TIPS) creation for preventing gastroesophageal variceal rebleeding remains controversial. Therefore, we performed a meta-analysis to compare the incidence of variceal rebleeding, shunt dysfunction, encephalopathy, and death between patients treated with TIPS alone and those treated with TIPS in combination with VE. Methods: We performed a literature search using PubMed, EMBASE, Scopus, and Cochrane databases for all studies comparing the incidence of complications between TIPS alone and TIPS with VE. The primary outcome was variceal rebleeding. Secondary outcomes include shunt dysfunction, encephalopathy, and death. Subgroup analysis was performed based on the type of stent (covered vs. bare metal). The random-effects model was used to calculate the relative risk (RR) with the corresponding 95% confidence intervals (CIs) of outcome. A P value < 0.05 was considered statistically significant. Results: Eleven studies with a total of 1,075 patients were included (597: TIPS alone and 478: TIPS plus VE). Compared to the TIPS alone, the TIPS with VE had a significantly lower incidence of variceal rebleeding (RR: 0.59, 95% CI: 0.43 - 0.81, P = 0.001). Subgroup analysis revealed similar results in covered stents (RR: 0.56, 95% CI: 0.36 - 0.86, P = 0.008) but there was no significant difference between the two groups in the subgroup analysis of bare stents and combined stents. There was no significant difference in the risk of encephalopathy (RR: 0.84, 95% CI: 0.66 - 1.06, P = 0.13), shunt dysfunction (RR: 0.88, 95% CI: 0.64 - 1.19, P = 0.40), and death (RR: 0.87, 95% CI: 0.65 - 1.17, P = 0.34). There were similarly no differences in these secondary outcomes between groups when stratified according to type of stent. Conclusions: Adding VE to TIPS reduced the incidence of variceal rebleeding in patients with cirrhosis. However, the benefit was observed with covered stents only. Further large-scale randomized controlled trials are warranted to validate our findings

Persistence of spike-specific immune responses in BNT162b2-vaccinated donors and generation of rapid ex-vivo T cells expansion protocol for adoptive immunotherapy: A pilot study

Introduction: The BNT162b2 mRNA-based vaccine has shown high efficacy in preventing COVID-19 infection but there are limited data on the types and persistence of the humoral and T cell responses to such a vaccine. Methods: Here, we dissect the vaccine-induced humoral and cellular responses in a cohort of six healthy recipients of two doses of this vaccine. Results and discussion: Overall, there was heterogeneity in the spike-specific humoral and cellular responses among vaccinated individuals. Interestingly, we demonstrated that anti-spike antibody levels detected by a novel simple automated assay (Jess) were strongly correlated (r=0.863, P<0.0001) with neutralizing activity; thus, providing a potential surrogate for neutralizing cell-based assays. The spike-specific T cell response was measured with a newly modified T-spot assay in which the high-homology peptide-sequences cross-reactive with other coronaviruses were removed. This response was induced in 4/6 participants after the first dose, and all six participants after the second dose, and remained detectable in 4/6 participants five months post-vaccination. We have also shown for the first time, that BNT162b2 vaccine enhanced T cell responses also against known human common viruses. In addition, we demonstrated the efficacy of a rapid ex-vivo T cell expansion protocol for spike-specific T cell expansion to be potentially used for adoptive-cell therapy in severe COVID-19, immunocompromised individuals, and other high-risk groups. There was a 9 to 13.7-fold increase in the number of expanded T cells with a significant increase of anti-spike specific response showing higher frequencies of both activation and cytotoxic markers. Interestingly, effector memory T cells were dominant in all four participants’ CD8+ expanded memory T cells; CD4+ T cells were dominated by effector memory in 2/4 participants and by central memory in the remaining two participants. Moreover, we found that high frequencies of CD4+ terminally differentiated memory T cells were associated with a greater reduction of spike-specific activated CD4+ T cells. Finally, we showed that participants who had a CD4+ central memory T cell dominance expressed a high CD69 activation marker in the CD4+ activated T cells.This research was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar, grant number MRC-01-21-113, and the Article Processing Charges was funded by Academic Health System, Medical Research Center, Hamad Medical Corporation, Doha, Qatar. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication