Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

Hereditary Ataxias in Cuba: A Nationwide Epidemiological and Clinical Study in 1001 Patients

The Cerebellum - The prevalence estimations of hereditary ataxias are biased since most epidemiological studies are confined to isolated geographical regions and few nationwide studies are...     

Mechanical Hemolysis Complicating Transcatheter Interventions for Valvular Heart Disease: JACC State-of-the-Art Review

Mechanical intravascular hemolysis is frequently observed following procedures on heart valves and uncommonly observed in native valvular disease. In most cases, its severity is mild. Nevertheless, it can be clinically significant and even life threatening, requiring multiple blood transfusions and renal replacement therapy. This paper reviews the current knowledge on mechanical intravascular hemolysis in valvular disease, before and after correction, focusing on pathophysiology, approach to diagnosis, and impact of other hematological conditions on the resultant anemia. The importance of a multidisciplinary management is underscored. Laboratory data are provided about subclinical hemolysis that is commonly observed following the implantation of surgical and transcatheter valve prostheses and devices. Finally, clinical scenarios are reviewed and current medical and surgical treatments are discussed, including alternative options for inoperable patients.     

Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting

International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...     

Impact of Socioeconomic Characteristics and Comorbidities on Therapy Initiation and Outcomes of Newly Diagnosed Multiple Myeloma: Real-World Data From a Resource-Constrained Setting

BackgroundOutcomes of newly diagnosed multiple myeloma (NDMM) in developing regions have not paralleled those in developed settings. Economic disadvantage, comorbidities, and aggressive disease behavior play competing roles on defining outcomes. Our aim was to analyze the impact of socioeconomic characteristics and comorbidities on therapy initiation, drug selection, and survival outcomes of NDMM in a resource-constrained setting.Patients and MethodsThis retrospective single-center cohort included ≥ 18-year-old NDMM patients from January 2006 to December 2018.ResultsA total of 245 patients were included with a median age of 62 years, Eastern Cooperative Oncology Group performance status ≤ 2 in 70.2%, International Staging System score ≥ 2 in 89.4%, and high-risk disease in 31.6%. Comorbidities were reported in 69.4%, and Charlson comorbidity index (CCI) was ≥ 2 in 64.1%. A total of 87.4% (n = 214) received thalidomide-, alkylating-, and bortezomib-based induction in 67.8%, 18.2%, and 13.1%. Patient-related factors including performance status, comorbidities, and CCI, but not myeloma-related factors, were associated with a decreased likelihood of initiating induction therapy. On multivariate analysis, CCI ≥ 2 remained statistically significant (odds ratio, 5.81; P = .005). Overall survival was 44 months. Although both patient- and myeloma-related factors were associated with a decreased overall survival, only International Staging System score > 2 (hazard ratio, 3.53; P = .004) and induction without bortezomib-based regimens (hazard ratio, 4.45; P < .001) were statistically significant on multivariate analysis.ConclusionMyeloma- and treatment-related factors are the main determinants of survival in NDMM induction-eligible patients. Patient-related factors play a pivotal role determining access to therapy and survival outcomes. Comorbidity index and performance status were determinant on defining therapy initiation in this real-world population, which emphasizes the need to improve health baseline conditions in resource-constrained settings.