Therapeutic Effect of Low-Molecular Weight Heparin and Incidence of Lower Limb Deep Venous Thrombosis and Pulmonary Embolism After Laparoscopic Bariatric Surgery

Background:The aim of our study was to determine the therapeutic effect of low-molecular weight heparin after laparoscopic Roux-en-Y gastric bypass.Methods:We prospectively analyzed data of 39 patients who underwent Roux-en-Y gastric bypass from 1093 consecutive patients who underwent bariatric procedures from May 1999 to May 2012. All patients were given 40 mg enoxaparin subcutaneously once daily preoperatively and continued for 5 days.Results:There were 31 females. Mean age was 32.48 years and mean body mass index was 44.59 kg/m(2). Only 46.1% of patients reached the defined therapeutic dose on the second day and 41% on the fifth day. One fatal pulmonary embolism was recorded (1/1093, 0.09%) in the entire series.Conclusions:Anti-Xa surveillance did not correlate strongly with outcome. Further studies are required for proper dose adjustments of low-molecular weight heparin in these obese patients and whether anti-Xa monitoring should be continued

Atherogenic Index of Plasma (AIP) a Tool to Assess Changes in Cardiovascular Disease Risk Post Laparoscopic Sleeve Gastrectomy

Predictive indices like the atherogenic index of plasma (AIP) have been developed to estimate the risk of cardiovascular disease (CVD). Metabolic surgery is the most effective treatment for a rapid improvement of morbid obesity and its comorbidities such as type 2 diabetes (T2D) and CVD. A decreased reoccurrence of CVD after metabolic surgery has been reported by several studies. However, studies utilizing predictive indices for CVD risk in CVD-free morbid-obese patients who undertook laparoscopic sleeve gastrectomy (LSG) are lacking. Here, we use AIP as a tool to evaluate the improvement in CVD risk post-LSG in morbid-obese people who had no history of CVD. Method. We compared baseline, 6- and 12-month post-LSG score of AIP, vascular age, circulating biochemical markers related to CVD in two groups of BMI and age-matched morbid-obese participants with and without T2D. Results. At baseline, people with T2D had significantly higher AIP both, with morbid obesity (0.23±0.06, p<0.001) and normal weight (0.022±0.05, p<0.001) compared to their BMI-matched without T2D group. People with morbid obesity had low AIP (−0.083±0.06). Vascular age was significantly higher in people with morbid obesity and T2D (65.8±3.7year, p<0.0001) compared to morbid obesity (37.9±2.6 year). After one year, AIP was significantly reduced compared to baseline score in people with morbid obesity with/without T2D, respectively (−0.135±0.07, p=0.003; and −0.36±0.04, p=0.0002). Conclusion. Our data illuminates AIP as a reliable predictive index for CVD risk in morbid-obese people who had no history of CVD. Moreover, AIP accurately distinguishes between morbid obesity with T2D and morbid obesity and showed a rapid and significant reduction in CVD risk after LSG in people who had no history of CVD. This is a ClinicalTrials.gov registered trial (Reference NCT03038373)

Prognostic impact of XPO1 mutations in metastatic non-small cell lung cancer (NSCLC)

e20533 Background: Nuclear protein transport is essential in guiding the organized traffic of important proteins and RNAs between the nucleus and cytoplasm of the cell. Export of proteins from the nucleus is exclusively regulated by Exportin 1(XPO1). In cancer, XPO1 is universally hyperactive and can promote the export of important tumor suppressors to the cytoplasm, leading to their functional inactivation. XPO1 is aberrantly over expressed in NSCLC and this over expression has been linked to poor overall survival. The underlying mechanisms of XPO1 over expression are not known. Currently there are no studies evaluating the impact of XPO1 mutations on NSCLC incidence and therapy resistance. Additionally, there are no studies that examined the XPO1 related pathways in NSCLC harboring co-alterations with other driver mutations such as EGFR or ALK. Methods: Tumor samples were analyzed using next-generation sequencing (NextSeq, 592 Genes), IHC, and whole transcriptome sequencing (WTS ,NovaSeq) (Caris Life Sciences, Phoenix, AZ). PD-L1 expression was tested by IHC using 22c3 (Dako) and TPS scores were reported (cutoff > 1%). TMB was measured by totaling somatic mutations (TMB-high cut-off ³ 10 mutations per Megabase). Gene fusions were detected by RNA sequencing using either the Archer FusionPlex panel or WTS. Survival was extracted from insurance claims data and calculated from time of tissue collection to last contact using Kaplan-Meier estimate. Statistical significance was determined using chi-square and Wilcoxon rank sum test and adjusted for multiple comparisons. Results: Among 18,218 NSCLC tumors sequenced, 26 harbored XPO1 mutations. XPO1 mutant tumors were more likely to be TMB High(79% vs. 52%, p = 0.007) and less likely to have high PDL1(32% vs. 68%, p = 0.03). KRAS mutations were seen in 19%(n = 5), EGFR mutation were rare (n = 2), and no targetable fusions were seen. Among the 17,449 NSCLC tumors with clinical data, there were 24 XPO1 mutant tumors with no histology imbalance observed in mutant vs. wild-type(WT). Comparison of survival in the NSCLC group between XPO1 mutant and WT showed a negative association with a hazard ratio(HR) of 1.932 (95% CI: 1.144- 3.264 p = 0.012). Comparing the survival within the subgroup with confirmed adenocarcinoma histology (9973 XPO1 WT and 14 XPO1 mutant) showed a similar negative correlation in survival with a HR of 2.156 (95% CI: 1.027- 4.525 P = 0.037). Conclusions: Presence of XPO1 pathogenic mutations was associated with a poor survival in both the entire NSCLC cohort and the adenocarcinoma subgroup. Further studies of this negative association at the molecular level along with effect of other co-existing mutations can result in development of novel treatment strategies

Impact of XPO1 mutations on survival outcomes in metastatic non-small cell lung cancer (NSCLC).

BACKGROUND: Nuclear protein transport is essential in guiding the traffic of important proteins and RNAs between the nucleus and cytoplasm. Export of proteins from the nucleus is mostly regulated by Exportin 1 (XPO1). In cancer, XPO1 is almost universally hyperactive and can promote the export of important tumor suppressors to the cytoplasm. Currently, there are no studies evaluating XPO1 amplifications and mutations in NSCLC and the impact on outcomes. METHODS: Tumor samples were analyzed using next-generation sequencing (NGS) (NextSeq, 592 Genes), immunohistochemistry (IHC), and whole transcriptome sequencing (WTS, NovaSeq) (Caris Life Sciences, Phoenix, AZ). Survival was extracted from insurance claims data and calculated from time of tissue collection to last contact using Kaplan-Meier estimate. RESULTS: Among 18,218 NSCLC tumors sequenced, 26 harbored XPO1 mutations and 24 had amplifications. XPO1 mutant tumors were more likely to have high TMB (79% vs. 52%, p = 0.007) and less likely to have high PD-L1 (32% vs. 68%, p = 0.03). KRAS co-mutations were seen in 19% (n = 5) and EGFR co-mutations were rare (n = 2). Among the 17,449 NSCLC tumors with clinical data, there were 24 XPO1 mutant. Comparison of survival between XPO1 mutant and WT showed a negative association with a hazard ratio (HR) of 1.932 (95% CI: 1.144-3.264 p = 0.012). XPO1 amplification was not associated with survival. CONCLUSIONS: XPO1 pathogenic mutations were associated with a poor survival in NSCLC. Although XPO1 mutations are rare in NSCLC, further studies to assess its associations with treatment responses are warranted