Tumor immune infiltration estimated from gene expression profiles predicts colorectal cancer relapse

A substantial fraction of patients with stage I-III colorectal adenocarcinoma (CRC) experience disease relapse after surgery with curative intent. However, biomarkers for predicting the likelihood of CRC relapse have not been fully explored. Therefore, we assessed the association between tumor infiltration by a broad array of innate and adaptive immune cell types and CRC relapse risk. We implemented a discovery-validation design including a discovery dataset from Moffitt Cancer Center (MCC; Tampa, FL) and three independent validation datasets: (1) GSE41258 (2) the Molecular Epidemiology of Colorectal Cancer (MECC) study, and (3) GSE39582. Infiltration by 22 immune cell types was inferred from tumor gene expression data, and the association between immune infiltration by each cell type and relapse-free survival was assessed using Cox proportional hazards regression. Within each of the four independent cohorts, CD4+ memory activated T cell (HR: 0.93, 95% CI: 0.90-0.96; FDR = 0.0001) infiltration was associated with longer time to disease relapse, independent of stage, microsatellite instability, and adjuvant therapy. Based on our meta-analysis across the four datasets, 10 innate and adaptive immune cell types associated with disease relapse of which 2 were internally validated using multiplex immunofluorescence. Moreover, immune cell type infiltration was a better predictors of disease relapse than Consensus Molecular Subtype (CMS) and other expression-based biomarkers (Immune-AICMCC:238.1-238.9; CMS-AICMCC: 241.0). These data suggest that transcriptome-derived immune profiles are prognostic indicators of CRC relapse and quantification of both innate and adaptive immune cell types may serve as candidate biomarkers for predicting prognosis and guiding frequency and modality of disease surveillance

Trauma sternotomy for presumed haemopericardium with incidental coccidioidal pericarditis

Background: Disseminated cocciodiomycosis with extrapulmonary disease occurs in less than 1% of infected patients, with few cases involving the pericardium reported in the literature. A subxiphoid window in a focussed assessment with sonography for trauma is a fast and reliable study for detecting haemopericardium in the haemodynamically unstable injured patient. Methods: Case report and literature review. Case report: A 50-year old man presented in extremis following a stab wound to the right thoracoabdominal region with a positive pericardial ultrasound. At the time of emergent sternotomy, the pericardial effusion appeared non-traumatic and not the cause of haemodynamic instability. Lung, diaphragm, liver and transverse colon lacerations were controlled by laparotomy. He was discovered to have extensive adenopathy within the mediastinum, porta hepatis, and lesser sac, which after histopathologic examination, demonstrated granulomatous lymphadenitis consistent with disseminated cocciodiomycosis. Conclusions: This case report describes the first reported “incidental” pericardial effusion in a haemodynamically unstable patient sustaining a thoracoabdominal stab wound discovered on a positive ultrasound study. Emergent operative exploration and subsequent workup determined the pericardial fluid to be of infectious origin, rather than traumatic. With the incidence of cocciodiomycosis within endemic geographic regions significantly rising, coccidioidal pericarditis may become an increasingly relevant cause of fluid detected on noninvasive pericardial examination. Keywords: Trauma, Infection, Focussed assessment with sonography for trauma (FAST

Clinical Tools for Rectal Cancer Response Assessment following Neoadjuvant Treatment in the Era of Organ Preservation

Local tumor response evaluation following neoadjuvant treatment(s) in rectal adenocarcinoma requires a multi-modality approach including physical and endoscopic evaluations, rectal protocoled MRI, and cross-sectional imaging. Clinical tumor response exists on a spectrum from complete clinical response (cCR), defined as the absence of clinical evidence of residual tumor, to near-complete response (nCR), which assumes a significant reduction in tumor burden but with increased uncertainty of residual microscopic disease, to incomplete clinical response (iCR), which incorporates all responses less than nCR that is not progressive disease. This article aims to review the clinical tools currently routinely available to evaluate treatment response and offers a potential management approach based on the extent of local tumor response

A Novel Nomogram for Early Identification and Intervention in Colorectal Cancer Patients at Risk for Malnutrition.

BACKGROUND: Malnutrition is under-recognized in cancer patients and can lead to poor treatment outcomes. We aim to develop an outpatient-focused score based on the Malnutrition Screening Tool (MST) to help identify colorectal cancer (CRC) profiles at high risk for malnutrition. METHODS: 506 CRC patients during initial outpatient oncology consultation at our tertiary referral outpatient oncology clinic completed the MST. Objective and subjective data were collected through chart review. Data gathered are as follows: demographics, anthropometrics, laboratory values, patient-reported symptoms, MST score, cancer history, performance status, socioeconomic status, and Charlson Comorbidity. Predictors of malnutrition were identified by logistic regression. Receiver operating curve (ROC), area under the curve (AUC), and our model\u27s predictability were determined. RESULTS: Significant predictors of malnutrition are as follows: younger age (20-39 vs \u3e40 years) (P = .007), normal-to-low body mass index at presentation (P = .019), Eastern Cooperative Oncology Group classification 2-3 (P = .012), metastatic disease (P = .046), albumin DISCUSSION: An outpatient clinic-derived malnutrition score obtained from objective and patient-reported variables may facilitate identification of CRC patients at highest risk for malnutrition. Rapid identification and intervention in high-risk patients may improve treatment recovery, therapy tolerance, and quality of life. Our tool requires external validation before application in clinical practice

Antisense Inhibitors Retain Activity in Pulmonary Models of <i>Burkholderia</i> Infection

The <i>Burkholderia cepacia</i> complex is a group of Gram-negative bacteria that are opportunistic pathogens in immunocompromised individuals, such as those with cystic fibrosis (CF) or chronic granulomatous disease (CGD). <i>Burkholderia</i> are intrinsically resistant to many antibiotics and the lack of antibiotic development necessitates novel therapeutics. Peptide-conjugated phosphorodiamidate morpholino oligomers are antisense molecules that inhibit bacterial mRNA translation. Targeting of PPMOs to the gene <i>acpP</i>, which is essential for membrane synthesis, lead to defects in the membrane and ultimately bactericidal activity. Exploration of additional PPMO sequences identified the ATG and Shine-Dalgarno sites as the most efficacious for targeting <i>acpP</i>. The CF lung is a complex microenvironment, but PPMO inhibition was still efficacious in an artificial model of CF sputum. PPMOs had low toxicity in human CF cells at doses that were antibacterial. PPMOs also reduced the bacterial burden in the lungs of immunocompromised CyBB mice, a model of CGD. Finally, the use of multiple PPMOs was efficacious in inhibiting the growth of both <i>Burkholderia</i> and <i>Pseudomonas</i> in an in vitro model of coinfection. Due to the intrinsic resistance of <i>Burkholderia</i> to traditional antibiotics, PPMOs represent a novel and viable approach to the treatment of <i>Burkholderia</i> infections