The effect of administering preprocedural VITamin K on the international normalized ratio in patients anticoagulated with ACEnocoumarol (VITKACE-study): a prospective cohort study.

BACKGROUND: The effect of the vitamin K antagonist acenocoumarol on coagulation needs to be reversed when patients undergo an invasive procedure with considerable bleeding risk. A strategy to achieve this is by administering oral vitamin K before a procedure while continuing acenocoumarol. OBJECTIVES: To assess the effect on periprocedural international normalized ratio (INR) values and safety using oral vitamin K as anticoagulant reversal method. METHODS: In this prospective cohort study, consecutive patients using acenocoumarol undergoing elective procedures between 2019 and 2022 were included. According to standard of care in our hospital, patients took 10 mg oral vitamin K 36 to 48 hours before the procedure while continuing their normal use of acenocoumarol. Effectiveness to lower INR to <1.8 preprocedural was assessed. Bleeding and thrombotic complications within 30 days after the procedure were assessed. Periprocedural course of INR was monitored by collecting additional blood samples. RESULTS: Seventy-four patients were included for analysis. On the day of the procedure, an adequate INR of <1.8 was achieved in 99% of patients. One clinically relevant nonmajor bleeding complication and no thrombotic complications were observed during the first 30 days after the procedure. INR gradually restored to therapeutic level during the days after the procedure. CONCLUSION: Using oral vitamin K while patients continue acenocoumarol intake is an effective way to adequately lower INR before an invasive procedure. Low amount of bleeding complications and absence of thromboembolic complications suggest that this is a safe strategy. The INR values returned gradually to therapeutic range after the procedure, probably contributing to the observed low bleeding rate.

CREB signaling activity correlates with differentiation and survival in medulloblastoma.

While there has been significant progress in the molecular characterization of the childhood brain cancer medulloblastoma, the tumor proteome remains less explored. However, it is important to obtain a complete understanding of medulloblastoma protein biology, since interactions between proteins represent potential new drug targets. Using previously generated phosphoprotein signaling-profiles of a large cohort of primary medulloblastoma, we discovered that phosphorylation of transcription factor CREB strongly correlates with medulloblastoma survival and associates with a differentiation phenotype. We further found that during normal cerebellar development, phosphorylated CREB was selectively expressed in differentiating cerebellar granule neuron progenitor (CGNP) cells. In line, we observed increased differentiation in CGNPs treated with Forskolin, Bmp6 and Bmp12 (Gdf7), which induce CREB phosphorylation. Lastly, we demonstrated that inducing CREB activation via PKA-mediated CREB signaling, but not Bmp/MEK/ERK mediated signalling, enhances medulloblastoma cell sensitivity to chemotherapy.

Identification of Two Protein-Signaling States Delineating Transcriptionally Heterogeneous Human Medulloblastoma.

The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma.

Single-incision and NOTES cholecystectomy, are there clinical or cosmetic advantages when compared to conventional laparoscopic cholecystectomy? A case-control study comparing single-incision, transvaginal, and conventional laparoscopic technique for cholecystectomy.

BACKGROUND: The aim of the present study was to compare the clinical and cosmetic results of transvaginal hybrid cholecystectomy (TVC), single-port cholecystectomy (SPC), and conventional laparoscopic cholecystectomy (CLC). Recently, single-incision laparoscopic surgery and natural orifice transluminal endoscopic surgery have been developed as minimally invasive alternatives for CLC. Few comparative studies have been reported. METHODS: Female patients with symptomatic gallstone disease who were treated in 2011 with SPC, TVC, or CLC were entered into a database. Patients were matched for age, body mass index, and previous abdominal surgery. After the operation all patients received a survey with questions about recovery, cosmesis, and body image. RESULTS: A total of 90 patients, 30 in each group, were evaluated. Median operative time for CLC was significantly shorter (p < 0.001). There were no major complications. Length of hospital stay, postoperative pain, and postoperative complications were not significantly different. The results for cosmesis and body image after the transvaginal approach were significantly higher. None of the sexually active women observed postoperative dyspareunia. CONCLUSIONS: Both SPC and TVC are feasible procedures when performed in selected patients. CLC is a faster procedure, but other clinical outcomes and complication rates were similar. SPC, and especially TVC, offer a better cosmetic result. Randomized trials are needed to specify the role of SPC and TVC in the treatment of patients with symptomatic gallstone disease.

Hybrid transvaginal cholecystectomy, clinical results and patient-reported outcomes of 50 consecutive cases.

OBJECTIVE: The aim of this study was to report the clinical and cosmetic results of transvaginal hybrid cholecystectomy (TVC). BACKGROUND: Natural orifice transluminal endoscopic surgery (NOTES) has been developed as a minimal invasive alternative for conventional laparoscopic cholecystectomy. Although transvaginal NOTES procedures are becoming increasingly popular, data focussing on body image, cosmesis and sexual recovery are rare. METHODS: Our clinic started to perform the TVC in the beginning of 2011. Female patients with symptomatic gallstone disease that were treated between January 2011 and April 2012 with TVC were entered in a prospective database. All patients received a survey postoperative with questions about recovery, cosmesis and body image. RESULTS: Fifty consecutive patients were treated with a TVC. There were no major complications. Mean operative time was 61 min. In five patients (10 %), a conversion to another type of cholecystectomy was necessary. None of the sexually active women observed dyspareunia postoperative. The results for cosmesis and body image after the transvaginal approach were excellent. CONCLUSIONS: TVC is a safe and feasible procedure when performed on selected patients. The transvaginal route seems to result in excellent cosmetic outcomes without gynaecologic complications after short-term follow up. Randomised trials are needed to specify the role of TVC in the treatment of patients with symptomatic gallstone disease and to detect differences in cosmetic outcomes.