Antiepileptic/teratogen valproate (VPA) is a histone deacetylase inhibitor/ epigenetic drug proposed for the antitumor therapy where it is generally crucial to target poorly or undifferentiated cells to prevent a recurrence. Transplanted rodent gastrulating embryos-proper (primitive streak and three germ layers) are the source of teratoma/teratocarcinoma tumors. Human primitive-streak remnants develop sacrococcygeal teratomas that may recur even when benign (well differentiated). To screen for unknown VPA impact on teratoma-type tumors, we used original 2-week embryoderived teratoma in vitro biological system completed by a spent media metabolome analysis. Gastrulating 9.5-day-old rat embryos-proper were cultivated in Eagle's minimal essential medium (MEM) with 50% rat serum (controls) or with the addition of 2 mM VPA. Spent media metabolomes were analyzed by FTIR. Compared to controls, VPA acetylated histones; significantly diminished overall teratoma growth, impaired survival, increased the apoptotic index, and decreased proliferation index and incidence of differentiated tissues (e.g., neural tissue). Control teratomas continued to grow and differentiate for 14 days in isotransplants in vivo, but in vitro VPA-treated teratomas resorbed. Principal component analysis of FTIR results showed that spent media metabolomes formed well-separated clusters reflecting the treatment and day of cultivation. In metabolomes of VPA-treated teratomas, we found elevation of previously described histone acetylation biomarkers [amide I a-helix and A(CH 3)/A(CH 2)]) with apoptotic biomarkers within the amide I region for b-sheets, and unordered and CH 2 vibrations of lipids. VPA may be proposed for therapy of the undifferentiated component of teratoma tumors and this biological system Abbreviations ASD, autism spectrum disorder; EC, embryonal carcinoma; GTS, growing teratoma syndrome; HDACi, histone deacetylase inhibitor; MEM, minimal essential medium; PCA, principal component analysis; PCNA, proliferating cell nuclear antigen; RMSEC, root mean square error of calibration; RMSECV, root mean square error of cross-validation; SAHA, suberoylanilidehydroxamic acid; VPA, valproate; WEC, whole rat embryo.

Objectives This study sought to determine (1) the association between the length of preoperative clopidogrel discontinuation, blood loss, and transfusion requirements and (2) whether preoperative platelet function testing predicts excessive postoperative bleeding in patients undergoing coronary artery bypass grafting (CABG) surgery. Methods In this retrospective analysis, patients undergoing CABG were divided into three groups with regard to the period between preoperative clopidogrel cessation and surgery: group 1 (n = 94, ≤3 days), group 2 (n = 100, 4–5 days), and group 3 (n = 83, 6–7 days), respectively. Impedance aggregometry (Multiplate) with arachidonic acid (ASPI) test assay (used for platelets stimulation) and adenosine diphosphate (ADP) test (used for platelets stimulation) was performed before the surgery. Primary outcome was 24 hours chest tube output (CTO) and transfusion requirements (red blood cell concentrate [RBCC], platelet concentrate [PC], fibrinogen concentrate [FC], and fresh-frozen plasma [FFP]) were considered as secondary outcomes. Results CTO during 24 hours was significantly higher in group 1 as compared with groups 2 and 3, respectively (p = 0.003). Considering secondary outcomes, RBCC (p = 0.043), PC (p = 0.001), FC (p = 0.003), and FFP (p = 0.010) were more frequently transfused in group 1 as compared with groups 2 and 3, respectively. Multiple electrode aggregometry ASPI and ADP tests were significantly correlated with the 24-hour CTO (ASPI test—rho = −0.258, p < 0.001; ADP test—rho = −0.164, p = 0.007). A significant correlation was observed between clopidogrel-free interval and 24-hour CTO (rho = −0.200, p < 0.001). Receiver-operating characteristics (ROC) curve analysis revealed cutoff values to delineate bleeding tendency (ASPI test ≤ 25 area under the aggregation curve [AUC], ADP test ≤63 AUC, and clopidogrel-free interval ≤3 days). Conclusion Excessive postoperative bleeding occurred less frequently if the period between clopidogrel discontinuation and surgery was longer than 3 days, as compared with shorter waiting time. Inadequate recovery of the platelets function following clopidogrel cessation in preoperative period was associated with increased bleeding risk. Platelet function testing was found to be a useful tool for postoperative bleeding management in our hands.

This is a brief communication stressing some critical points associated with cystic nodal metastasis (CNM) in human papillomavirus (HPV) positive oropharyngeal squamous cell carcinoma (OPSCC) and its implication on treatment protocols and outcomes.

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