Identifying robust, patient-specific, and predictive biomarkers presents a major obstacle in precision oncology. To optimize patient-specific therapeutic strategies, here we couple pathway knowledge with large-scale drug sensitivity, RNAi, and CRISPR-Cas9 screening data from 460 cell lines. Pathway activity levels are found to be strong predictive biomarkers for the essentiality of 15 proteins, including the essentiality of MAD2L1 in breast cancer patients with high BRCA-pathway activity. We also find strong predictive biomarkers for the sensitivity to 31 compounds, including BCL2 and microtubule inhibitors (MTIs). Lastly, we show that Bcl-xL inhibition can modulate the activity of a predictive biomarker pathway and re-sensitize lung cancer cells and tumors to MTI therapy. Overall, our results support the use of pathways in helping to achieve the goal of precision medicine by uncovering dozens of predictive biomarkers.

Background: Endoscopic vacuum-assisted closure (EVAC) therapy is increasingly being used as a new promising method for repairing upper gastrointestinal defects of different etiologies with high success rates. EVAC therapy consists of placing a sponge either within the lumen or within an abscess cavity connected with a nasogastric (NG) tube to a negative pressure system, thus decreasing bacterial contamination and edema and promoting granulation tissue proliferation, thereby gradually decreasing the cavity size until complete closure. Herein, we describe a modified technique for EVAC therapy in which the NG tube is passed into the esophagus through an existing intrapleural drain tract using a rendezvous technique. The small residual fistula was amendable to fibrin glue embolization. This allows easier sponge placement and exchange compared to traditional EVAC technique, and allows oral intake during treatment. We also review the literature regarding other endoscopic treatment options for esophageal anastomotic leaks and perforations. Methods: The PubMed database was searched using the terms “esophagus,” “esophageal,” “leak,” “fistula,” “endoluminal vacuum-assisted closure (VAC),” “endoscopic VAC,” “stent,” “sealant,” “glue,” and “over-the-scope clip (OTSC).” Reference lists of identified articles were searched for further articles, and the “similar articles” function was used on all included articles. Results: Complete closure of the nonhealing fistula was achieved after 8 days of EVAC treatment and fibrin glue embolization. Conclusions: Modified EVAC technique as described is feasible and safe. To the best of our knowledge, this is the first description of this technique. The technique allows easier sponge placement and exchange compared to traditional EVAC technique, and allows oral intake during treatment.

To evaluate the accuracy of high cytomegalovirus (CMV) specific IgG avidity in excluding recent infection in patients with anti-CMV IgM antibodies detected during the first trimester, using amniotic fluid obtained by standard amniocentesis. Records of all patients with a positive anti-CMV IgM with IgG avidity >65% detected during pregnancy were reviewed. Amniocentesis for CMV assessment was offered to all patients. The presence of the virus in amniotic fluid was determined by polymerase chain reaction (PCR) and shell vial testing. Seventy-nine patients with a positive CMV IgM-high IgG avidity combination were identified. The serological tests were performed during the first trimester in 65 (82.3%) patients, of which 28 consented and underwent amniocentesis. All amniotic fluid samples were negative for CMV-PCR and CMV shell vial testing. IgG avidity above 65% is a good indicator of past infection, and thus excludes CMV in the amniotic fluid. In such circumstances, invasive prenatal diagnosis may eventually not be required. This optimistic conclusion, however, needs to be confirmed by large scale studies.

Metabolic syndrome is a group of disorders which include obesity, diabetes, dyslipidemias, and hypertension. This condition is rapidly increasing in an aging population. The rates of surgery in older patients is also growing and a wide range of operations including minimally invasive procedures is now available for this segment of the population. The number of patients suffering from postoperative adhesions is therefore correspondingly increasing. In addition to preventing and treating the metabolic disease itself, improved therapeutic strategies for the prevention of surgical adhesions have to be developed. Here we review the existing and novel treatment options.