Interconnectivity between molecular subtypes and tumor stage in colorectal cancer

BACKGROUND: There are profound individual differences in clinical outcomes between colorectal cancers (CRCs) presenting with identical stage of disease. Molecular stratification, in conjunction with the traditional TNM staging, is a promising way to predict patient outcomes. We investigated the interconnectivity between tumor stage and tumor biology reflected by the Consensus Molecular Subtypes (CMSs) in CRC, and explored the possible value of these insights in patients with stage II colon cancer. METHODS: We performed a retrospective analysis using clinical records and gene expression profiling in a meta-cohort of 1040 CRC patients. The interconnectivity of tumor biology and disease stage was assessed by investigating the association between CMSs and TNM classification. In order to validate the clinical applicability of our findings we employed a meta-cohort of 197 stage II colon cancers. RESULTS: CMS4 was significantly more prevalent in advanced stages of disease (stage I 9.8% versus stage IV 38.5%, p < 0.001). The observed differential gene expression between cancer stages is at least partly explained by the biological differences as reflected by CMS subtypes. Gene signatures for stage III-IV and CMS4 were highly correlated (r = 0.77, p < 0.001). CMS4 cancers showed an increased progression rate to more advanced stages (CMS4 compared to CMS2: 1.25, 95% CI: 1.08-1.46). Patients with a CMS4 cancer had worse survival in the high-risk stage II tumors compared to the total stage II cohort (5-year DFS 41.7% versus 100.0%, p = 0.008). CONCLUSIONS: Considerable interconnectivity between tumor biology and tumor stage in CRC exists. This implies that the TNM stage, in addition to the stage of progression, might also reflect distinct biological disease entities. These insights can potentially be utilized to optimize identification of high-risk stage II colo

Mortality and surgery-related complications in very low and extreme low birth weight infants treated for esophageal atresia:a multi-center cohort study

Introduction: Surgical esophageal atresia (EA) repair is a complex operation with high risk of perioperative complications. Infants born with very low or extreme low birth weight (VLBW or ELBW) might be even at higher risk for developing perioperative complications. However, studies about this specific patient group are scarce, resulting in a knowledge gap on the outcomes of these infants. This hampers identifying the optimal treatment strategy, but also good counselling of parents. The aim of this study was to evaluate the mortality and surgery-related complication rates of VLBW and ELBW infants with EA after surgical esophageal repair in a multi-center cohort. Methods: A multi-center retrospective cohort study was performed in five academic hospitals in the Netherlands. Data was extracted from the medical record of patients born with EA and birthweight 1000–1500 g (VLBW) or &lt;1000 g (ELBW) between 2000 and 2019. The main outcomes were overall mortality and specific surgery-related morbidity 90 days postoperative. Only descriptive analyses were performed. Results: In total, 44 children were born with EA and VLBW/ELBW, of which 39 were included who underwent EA repair, 10 ELBW and 29 VLBW. Of the 39 infants, 25 had additional congenital anomalies. Six out of 29 VLBW infants and three out of 10 ELBW infants deceased. Complications occurred in 17 VLBW and two ELBW infants. Anastomotic stricture was the most frequent complications (VLBW n = 12, ELBW n = 1), others were anastomotic leakage (VLBW n = 5, ELBW n = 0), pneumothorax (VLBW n = 5, ELBW n = 0), surgical site infection (VLBW n = 1, ELBW n = 1) and recurrent fistula (VLBW n = 0, ELBW n = 1). Conclusion: Mortality and surgery-related complication rates in VLBW/ELBW infants after surgical EA repair in this large cohort are in line with previous studies. However, outcomes after surgical repair of EA are worse compared to infants born with a normal birthweight. This information is important to consider during parent counseling and multidisciplinary consultation.</p

Communicating with conscious and mechanically ventilated critically ill patients: a systematic review

BACKGROUND: Ventilator-dependent patients in the ICU often experience difficulties with one of the most basic human functions, namely communication, due to intubation. Although various assistive communication tools exist, these are infrequently used in ICU patients. We summarized the current evidence on communication methods with mechanically ventilated patients in the ICU. Secondly, we developed an algorithm for communication with these patients based on current evidence. METHODS: We performed a systematic review. PubMed, Embase, Cochrane, Cinahl, PsychInfo, and Web of Science databases were systematically searched to November 2015. Studies that reported a communication intervention with conscious nonverbal mechanically ventilated patients in the ICU aged 18 years or older were included. The methodological quality was assessed using the Quality Assessment Tool. RESULTS: The search yielded 9883 publications, of which 31 articles, representing 29 different studies, fulfilled the inclusion criteria. The overall methodological quality varied from poor to moderate. We identified four communication intervention types: (1) communication boards were studied in three studies—they improved communication and increased patient satisfaction, but they can be time-consuming and limit the ability to produce novel utterances; (2) two types of specialized talking tracheostomy tubes were assessed in eight studies—audible voicing was achieved in the majority of patients (range 74–100 %), but more studies are needed to facilitate safe and effective use; (3) an electrolarynx improved communication in seven studies—its effectiveness was mainly demonstrated with tracheostomized patients; and (4) “high-tech” augmentative and alternative communication (AAC) devices in nine studies with diverse computerized AAC devices proved to be beneficial communication methods—two studies investigated multiple AAC interventions, and different control devices (e.g., touch-sensitive or eye/blink detection) can be used to ensure that physical limitations do not prevent use of the devices. We developed an algorithm for the assessment and selection of a communication intervention with nonverbal and conscious mechanically intubated patients in the ICU. CONCLUSIONS: Although evidence is limited, results suggest that most communication methods may be effective in improving patient–healthcare professional communication with mechanically ventilated patients. A combination of methods is advised. We developed an algorithm to standardize the approach for selection of communication techniques. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-016-1483-2) contains supplementary material, which is available to authorized users

The recurring features of molecular subtypes in distinct gastrointestinal malignancies—A systematic review

In colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC) and gastric cancer (GC) multiple studies of inter-tumor heterogeneity have identified molecular subtypes, which correlate with clinical features. Our aim was to investigate the attributes of molecular subtypes across three different gastrointestinal cancer types. We performed a systematic search for publications on molecular subtypes or classifications in PDAC and GC and compared the described subtypes with the established consensus molecular subtypes of CRC. Examining the characteristics of subtypes across CRC, PDAC and GC resulted in four categories of subtypes. We describe uniting and distinguishing features within a mesenchymal, an epithelial, an immunogenic and a metabolic and digestive subtype category. We conclude that molecular subtypes of CRC, PDAC and GC display relevant overlap in molecular features and clinical outcomes. This finding encourages quantitative studies on subtypes across different cancer types and could lead to a paradigm shift in future treatment strategies

Additional file 2: of Communicating with conscious and mechanically ventilated critically ill patients: a systematic review

is a table presenting critical appraisal assessment of the methodological quality of the studies using the Quality Assessment Tool (QATSDD); range 0–42). (PDF 287 kb