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Clot in Transit on Transesophageal Echocardiography in a Prone Patient with COVID-19 Acute Respiratory Distress Syndrome [Case Report]

Horowitz, James M; Yuriditsky, Eugene; Henderson, Ian J; Stachel, Maxine Wallis; Kwok, Benjamin; Saric, Muhamed
•The risk of thromboembolic events in COVID-19 is substantial•Pulmonary embolism should be considered in cases of clinical deterioration•Management of clot in transit is controversial.
PMCID:7229961
PMID: 32426575
ISSN: 2468-6441
CID: 4444112

Alvimopan for the Prevention of Postoperative Ileus in Inflammatory Bowel Disease Patients

Jang, Janice; Kwok, Benjamin; Zhong, Hua; Xia, Yuhe; Grucela, Alexis; Bernstein, Mitchell; Remzi, Feza; Hudesman, David; Chen, Jingjing; Axelrad, Jordan; Chang, Shannon
BACKGROUND:Postoperative ileus (POI) is a temporary delay of coordinated intestinal peristalsis. Alvimopan, an oral peripherally acting mu-opioid receptor antagonist approved for accelerating gastrointestinal recovery, has never been studied specifically in patients with inflammatory bowel disease (IBD). AIM/OBJECTIVE:To investigate the efficacy of alvimopan in preventing POI among IBD patients. METHODS:A retrospective chart review was conducted on 246 IBD patients undergoing bowel surgery between 2012 and 2017. Data collected included demographics, IBD subtype, length of stay (LOS), postoperative gastrointestinal symptoms, and administration of alvimopan. The primary outcome was POI; secondary gastrointestinal recovery outcomes were: time to first flatus, time to first bowel movement, time to tolerating a liquid diet, time to tolerating solid food, and LOS. RESULTS:When compared with the control group, patients in the alvimopan group had shorter times to tolerating liquids and solids, first flatus, and first bowel movements (p < 0.01). LOS was shorter in the alvimopan group when compared with controls (p < 0.01). The overall incidence of POI was higher in controls than in the alvimopan group (p = 0.07). For laparoscopic surgeries, the incidence of POI was also higher in controls than in the alvimopan group (p < 0.01). On multivariable analysis, alvimopan significantly decreased time to all gastrointestinal recovery endpoints when compared to controls (p < 0.01). CONCLUSIONS:Alvimopan is effective in accelerating time to gastrointestinal recovery and reducing POI in IBD patients. While the benefits of alvimopan have been demonstrated previously, this is the first study of the efficacy of alvimopan in IBD patients.
PMID: 31522323
ISSN: 1573-2568
CID: 4097752

Utility of Regional Airway Epithelial Cells for Lung Cancer Biomarker [Meeting Abstract]

Kwok, B.; Chiang, V.; Thomas, S.; Alapaty, S.; Yie, T.; Rom, W. N.; Tsay, J.
ISI:000466776702414
ISSN: 1073-449x
CID: 5266082

Differential Regulation of ZEB1 and EMT by MAPK-Interacting Protein Kinases (MNK) and eIF4E in Pancreatic Cancer

Kumar, Krishan; Chow, Christina R; Ebine, Kazumi; Arslan, Ahmet D; Kwok, Benjamin; Bentrem, David J; Eckerdt, Frank D; Platanias, Leonidas C; Munshi, Hidayatullah G
UNLABELLED:Human pancreatic ductal adenocarcinoma (PDAC) tumors are associated with dysregulation of mRNA translation. In this report, it is demonstrated that PDAC cells grown in collagen exhibit increased activation of the MAPK-interacting protein kinases (MNK) that mediate eIF4E phosphorylation. Pharmacologic and genetic targeting of MNKs reverse epithelial-mesenchymal transition (EMT), decrease cell migration, and reduce protein expression of the EMT-regulator ZEB1 without affecting ZEB1 mRNA levels. Paradoxically, targeting eIF4E, the best-characterized effector of MNKs, increases ZEB1 mRNA expression through repression of ZEB1-targeting miRNAs, miR-200c and miR-141. In contrast, targeting the MNK effector hnRNPA1, which can function as a translational repressor, increases ZEB1 protein without increasing ZEB1 mRNA levels. Importantly, treatment with MNK inhibitors blocks growth of chemoresistant PDAC cells in collagen and decreases the number of aldehyde dehydrogenase activity-positive (Aldefluor+) cells. Significantly, MNK inhibitors increase E-cadherin mRNA levels and decrease vimentin mRNA levels in human PDAC organoids without affecting ZEB1 mRNA levels. Importantly, MNK inhibitors also decrease growth of human PDAC organoids. IMPLICATIONS/CONCLUSIONS:These results demonstrate differential regulation of ZEB1 and EMT by MNKs and eIF4E, and identify MNKs as potential targets in pancreatic cancer.
PMCID:4755915
PMID: 26609108
ISSN: 1557-3125
CID: 5266042

GLI2-dependent c-MYC upregulation mediates resistance of pancreatic cancer cells to the BET bromodomain inhibitor JQ1

Kumar, Krishan; Raza, Sania S; Knab, Lawrence M; Chow, Christina R; Kwok, Benjamin; Bentrem, David J; Popovic, Relja; Ebine, Kazumi; Licht, Jonathan D; Munshi, Hidayatullah G
JQ1 and I-BET151 are selective inhibitors of BET bromodomain proteins that have efficacy against a number of different cancers. Since the effectiveness of targeted therapies is often limited by development of resistance, we examined whether it was possible for cancer cells to develop resistance to the BET inhibitor JQ1. Here we show that pancreatic cancer cells developing resistance to JQ1 demonstrate cross-resistance to I-BET151 and insensitivity to BRD4 downregulation. The resistant cells maintain expression of c-MYC, increase expression of JQ1-target genes FOSL1 and HMGA2, and demonstrate evidence of epithelial-mesenchymal transition (EMT). However, reverting EMT fails to sensitize the resistant cells to JQ1 treatment. Importantly, the JQ1-resistant cells remain dependent on c-MYC that now becomes co-regulated by high levels of GLI2. Furthermore, downregulating GLI2 re-sensitizes the resistant cells to JQ1. Overall, these results identify a mechanism by which cancer cells develop resistance to BET inhibitors.
PMCID:4452877
PMID: 25807524
ISSN: 2045-2322
CID: 5266032