The clinical application of ctDNA to predict response to neoadjuvant chemoradiotherapy in patients with locally-advanced rectal cancer

Abstract Colorectal cancer is a major cause of cancer-related deaths worldwide. A third of colorectal cancers reside in the rectum. Many patients with rectal cancer present in the locally-advanced stage which needs multi-modality therapy usually starting with neoadjuvant chemo-radiotherapy followed by surgery and adjuvant systemic chemotherapy. Total neoadjuvant therapy, defined as the preoperative administration of both neoadjuvant chemoradiotherapy and systemic chemotherapy is also an evolving treatment that can be delivered if indications for preoperative chemotherapy exist. Identifying biomarkers to predict response to neoadjuvant therapy, can improve patient selection for a non-surgical, active surveillance approach. Circulating tumor DNA (ctDNA) can be detected in about 75% of patients with locally-advanced rectal cancer (LARC) at the baseline and in about 15–20% of patients in the post-neoadjuvant, or postoperative setting. ctDNA clearance rate after delivering neoadjuvant chemoradiotherapy, or integrating baseline ctDNA with other conventional markers of clinical response can be a promising marker to select and monitor patients on the “watch and wait” approach. In this article, we aimed to integrate the recent findings and provide a unique insight into the utilization of preoperative ctDNA to predict clinical response in patients with LARC. We also sought to highlight the potential areas for future research in this field. Further studies with a larger number of participants from diverse populations and settings are needed to increase external validity of such investigations and determine the role of ctDNA in guiding clinical decisions and management of patients with LARC

7-year outcomes in diabetic patients after coronary artery bypass graft in a developing country

Abstract Background Revascularization in diabetic patients with coronary artery disease remains a challenge in cardiology practice. Although clinical trials have reported the mid-term superiority of coronary artery bypass grafting (CABG) surgery over percutaneous coronary intervention in these patients, little is known about the long-term outcomes of CABG in diabetic patients compared to non-diabetics, particularly in developing countries. Methods Between 2007 and 2016, we recruited all patients who underwent isolated CABG in a tertiary care cardiovascular center in a developing country. The patients were followed at 3–6 months and 12 months after surgery, and then annually. The study endpoints were 7-year all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE). Results Of 23,873 patients (17,529 males, mean age 65.67 years) who underwent CABG, 9227 (38.65%) patients were diagnosed with diabetes. After adjustment for potential confounders, patients with diabetes experienced a 31% increase in MACCE seven years after surgery compared to the non-diabetic patients (HR = 1.31, 95% CI: 1.25–1.38, P-value < 0.0001). Meanwhile, diabetes contributes to a 52% increase in the risk of all-cause mortality after CABG (HR = 1.52, 95% CI: 1.42–1.61, P-value < 0.0001). Conclusions Our study showed a higher risk of all-cause mortality and MACCE at seven years in diabetic patients undergoing isolated CABG. The outcomes in the studied center in a developing country were comparable to western centers. The high incidence of adverse outcomes in the long term in diabetic patients implies that not only short-term but long-term measures should be taken to improve the CABG outcomes in this challenging patient population

Percent of main outcome in patients by different category of nephrotoxic treatment and incidence of acute kidney injury (AKI).

(Group 1: Without AKI and without antiviral medications (n = 362); Group 2: Without AKI and with antiviral medications (n = 358); Group 3: With AKI and without antiviral medications (n = 38); Group 4: With AKI and with antiviral medications (n = 75)).</p

Logistic regression and odds ratio for different category of antiviral treatment and incidence of acute kidney injury and mortality, intensive care unit admission and prolonged hospitalization.

Logistic regression and odds ratio for different category of antiviral treatment and incidence of acute kidney injury and mortality, intensive care unit admission and prolonged hospitalization.</p

Kaplan Maier survival time of patients based on different category of antiviral treatment and incidence of acute kidney injury (AKI).

(Group 1: Without AKI and Without antiviral medications (n = 362); Group 2: Without AKI and with antiviral medications (n = 358); Group 3: With AKI and without antiviral medications (n = 38); Group 4: With AKI and With antiviral medications (n = 75)).</p

Clinical characteristics of patients included in the study based on antiviral treatment and incidence of acute kidney injury.

Clinical characteristics of patients included in the study based on antiviral treatment and incidence of acute kidney injury.</p

Mortality, intensive care unit admission and prolonged hospitalization of patients included in the study based on different categories of antiviral treatment and incidence of acute kidney injury.

Mortality, intensive care unit admission and prolonged hospitalization of patients included in the study based on different categories of antiviral treatment and incidence of acute kidney injury.</p

Prescribed medications in patients in different group of antiviral treatment and incidence of acute kidney injury.

Prescribed medications in patients in different group of antiviral treatment and incidence of acute kidney injury.</p

Flow diagram of study selection and outcomes.

Abbreviations: COVID-19: coronavirus disease 2019; AKI: acute kidney injury; ICU: intensive care unit. *Duration of prolonged hospitalization defined as higher than median (six days).</p

Clinical characteristics of patients included in the study based on antiviral treatment.

Clinical characteristics of patients included in the study based on antiviral treatment.</p