OBJECTIVES: Literature is emerging regarding the role of center volume as an independent variable contributing to improved outcomes. A higher volume of index procedures may be associated with decreased morbidity and mortality. This association has not been examined for the subgroup of infants with congenital diaphragmatic hernia (CDH) receiving extracorporeal life support (ECLS). Our study aims to examine the risk-adjusted association between center volume and outcomes in CDH-ECLS neonates, hypothesizing that higher center volume confers a survival advantage. DESIGN: Multicenter, retrospective comparative study using the Extracorporeal Life Support Organization database. SETTING: One hundred twenty international pediatric centers. PATIENTS: Neonates with CDH managed with ECLS from 2000 to 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The cohort included 4,985 neonates with a mortality rate of 50.6%. For the 120 centers studied, mean center volume was 42.4 ± 34.6 CDH ECLS cases over the 20-year study period. In an adjusted model, higher ECLS volume was associated with lower odds of mortality: odds ratio (OR) 0.995 (95% CI, 0.992–0.999; p = 0.014). For an increase in one sd in volume, that is, 1.75 cases annually, the OR for mortality was lower by 16.7%. Volume was examined as a categorical exposure variable where low-volume centers (fewer than 2 cases/yr) were associated with 54% higher odds of mortality (OR, 1.54; 95% CI, 1.03–2.29) compared with high-volume centers. On-ECLS complications (mechanical, neurologic, cardiac, hematologic metabolic, and renal) were not associated with volume. The likelihood of infectious complications was higher for low- (OR, 1.90; 95% CI, 1.06–3.40) and medium-volume (OR, 1.87; 95% CI, 1.03–3.39) compared with high-volume centers. CONCLUSIONS: In this study, a survival advantage directly proportional to center volume was observed for CDH patients managed with ECLS. There was no significant difference in most complication rates. Future studies should aim to identify factors contributing to the higher mortality and morbidity observed at low-volume centers.
Overnight radiology coverage for pediatric trauma patients (PTPs) is addressed with a combination of on-call radiology residents (RRs) and/or attending teleradiologists (ATs); however, the accuracy of these two groups has not been investigated for PTPs. We aimed to compare the accuracy of RRs vs AT interpretations of computed tomography (CT) scans for PTPs.
Difficulty in primary fascial closure of the abdomen in transplant patients is a common challenge. Abdominal wall tension may have detrimental effects on the newly transplanted graft due to compression, and blood flow hindrance, potentially leading to ischemia or thrombosis and possibly graft failure. Furthermore, patients will be at risk of developing fascial ischemia and dehiscence. Myocutaneous flaps, temporary closure with silastic mesh, abdominal wall transplants, and even graft reduction, bowel resection, and splenectomies have been practiced with varying degrees of success. In this study, we present four cases of patients who underwent orthotopic liver transplantation (OLT) with bridging Vicryl knitted mesh (ETHICON VKML VICRYL-Polyglactin 910-30 × 30 cm) to relieve the tension during the closure. Our results show that these patients, despite having a high average Model End-Stage Liver Disease (MELD) score of 25, had a good liver function at the time of discharge and continue to upon follow-up. They had a relatively short length of stay (LOS) in both the intensive care unit (ICU) and in the hospital, an average of 3.5 days and 9 days, respectively. Our case series successfully show that utilizing a bridging Vicryl knitted mesh is a reasonable approach to attain tension-free abdominal closure in OLT with satisfying results.
After a patient's tumor is removed, he/she undergoes adjuvant chemotherapy and/or radiotherapy. Both of these treatments lead to formation of resistant cells that become metastatic cancer cells. The cellular program responsible for the change of epithelial tumors (such as breast, colorectal, pancreatic, and ovarian) into metastatic mesenchymal cell types is Epithelial‐Mesenchymal Transition (EMT). EMT is a normal process during embryogenesis, where epithelial cells lose their characteristics and become motile mesenchymal cells. Invasive and metastatic characteristics of carcinoma cells in primary tumors are mediated by EMT. During EMT, the primary tumor cells lose cell‐cell adhesion, normally mediated by E‐cadherin, and attain mesenchymal markers. The cells exhibit increased intercellular separation and elongated shape with pseudopodia. We developed a chemoresistant colorectal cancer cell line (DLD‐1 OxR) by exposing DLD‐1 colorectal cancer cells to increasing concentrations of oxaliplatin (a chemotherapy drug used for colorectal cancer). DLD‐1 OxR cells exhibit increased intercellular separation, increased motility, and elongated spindle shape with pseudopodia. MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression postranscriptionally. MiRNA, with silencing complexes, bind 3′ untranslated regions which lead to degradation of RNA or translation repression. Recent studies show that miRNA‐200 family members regulate the EMT process and metastasis. Decreased expression of miRNA‐200 family members leads to metastatic transformation of cancer cells. One of the miRNA‐200 family members is miRNA‐200c. Our hypothesis is that miRNA‐200c expression is decreased in DLD‐1 OxR cells. Loss of miRNA‐200c leads to expression of several regulatory genes involved in EMT, such as, Suz12 (one of the polycomb repressive complex proteins) and claudin‐1 (an integral membrane protein). We have found that miRNA‐200c expression is lower in DLD‐1 OxR cells compared to the parental DLD‐1 cells. Also, the miRNA‐200c targets are upregulated in DLD‐1 OxR. In conclusion, our study suggests that miRNA‐200c is involved in the EMT process in colorectal cancer cells. Support or Funding Information KS and AM are supported by the DeNardo Education and Research Foundation.
In 2012, colorectal cancer was the second most common cancer diagnosed in women and the third most common in men. In 2015, an estimated 132,700 new individuals will be diagnosed and 49,700 people will die from the disease. Colorectal cancer, though one of the most common cancers worldwide, is not distributed evenly among the world's population. It is concentrated mainly in countries with a Western culture, specifically the Western diet, such as the United States and Western Europe. A considerably smaller rate of incidence of disease is found in Africa and parts of Asia. This difference in colorectal cancer distribution may be attributed to the increased presence of certain phytochemicals in non‐Western diets. Our hypothesis is that phytochemicals inhibit proliferation of both metastatic and non‐metastatic cancer cell lines. Studies have shown that transdifferentiation into epithelial‐mesenchymal transition (EMT) by chemotherapy leads to the formation of resistant cells. EMT is a process in which epithelial cells acquire a mesenchymal phenotype, characterized by increased migratory and invasive properties. We developed a chemoresistance‐induced epithelial to mesenchymal transitioned colon cancer cell line (DLD‐1 OxR) by exposing the parental cell line (DLD‐1) to increasing concentrations of oxaliplatin (a drug used in the treatment of metastatic colon cancer). The DLD‐1 OxR cell line has undergone EMT and lost its epithelial properties to become a more motile mesenchymal cell type. We used a wound healing assay and transwell assay to assess the migration and invasion of the EMT‐chemoresistant cell line respectively. DLD‐1 and DLD‐1 OxR cells were exposed to curcumin and kaempferol. Curcumin is a phytochemical derived from turmeric, which has been shown to suppress inflammation and inhibit cell proliferation. Kaempferol, a phytochemical found in plants such as broccoli, kale, beans, and leeks, has also shown anti‐inflammatory and anti‐cancerous activity. Both phytochemicals inhibited proliferation of DLD‐1 and DLD‐1 OxR cell lines. Support or Funding Information KM, KS, and AM are supported by the DeNardo Education and Research Foundation Fellowship.
