In the early stage of drug discovery, thousands of new chemical entities (NCEs) may be screened before a single drug candidate can be identified for development. In order to accelerate the drug discovery process, we have developed higher-throughput enzyme assays to evaluate the inhibition of cytochrome P450 isoforms 2D6 (CYP2D6) and 3A4 (CYP3A4) in human liver microsomes. The assays are based on high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) techniques. The analysis time for each sample was reduced from $20 minutes for the conventional HPLC assay to 30 seconds for the LC/MS/MS assay. For both LC/MS/MS assays, the linearity (r 2 b 0.99), precision (%CV`15%) and accuracy (% bias 15%) for both inter-and intraday validations were satisfactory. Since the implementation of the LC/ MS/MS assays, our sample throughput has increased by over 40-fold.

Malignant mesothelioma (MM) is a rare form of cancer. Its histopathological diagnosis is very difficult, as it exhibits a number of different appearances that can be misinterpreted as metastatic invasion or atypical hyperplasia. Thus, there is an urgent need to identify adequate markers to distinguish between benign and malignant cells, allowing the implementation of appropriate therapies and, possibly, specific directed therapies. MM, like other tumors, show an increase in glucose uptake, due to high rates of glycolysis, inducing an intracellular overload of acids. In this context, monocarboxylate transporters (MCTs) emerge as important players, by mediating the transmembranar co-transport of lactate with a proton, thereby, regulating pH and allowing continuous glycolysis. Importantly, proper MCT expression and activity depend on its co-expression with a chaperone, CD147, which is associated with poor prognosis in cancer. Twenty-two samples including reactive mesothelial cells, MM, and atypical mesothelial hyperplasias were evaluated for immunoexpression of MCT1, MCT4, and CD147. Expression of these proteins was compared with GLUT1 as a new promising marker for MM. Although MCT isoforms were not differentially expressed in the two types of cytological specimens, CD147, as GLUT1, was almost exclusively expressed in MM. Both MCT1 and MCT4 are not able to discriminate between mesothelial reactive cells and mesothelial malignant cells, while CD147 was able to distinguish these two proliferations. If confirmed, besides being a good marker for identification of MM, CD147 may also be a target for therapeutical strategies in this rare type of tumor.

Objectives Endarterectomy is the treatment of choice for arterial occlusive disease of the femoral bifurcation. Longitudinal arteriotomy and prosthetic patch angioplasty is the standard technique but, due to the increasing concerns with prosthetic-related infections and multidrug-resistant pathogens our group adopted an alternative approach. We present our experience with eversion femoral endarterectomy. Methods All patients submitted to eversion femoral endarterectomy in a single institution during 2016–2019 were retrospectively analyzed. Patient demographics, surgical data, and complications were captured from medical records. Results Nineteen patients, 84.2% male and a median age of 67 years (IQR 62–78) were submitted to eversion femoral endarterectomy with a median follow-up of 180 days (IQR 71–395). Seventeen (89.4%) patients were treated for chronic limb ischemia and the other two were submitted to femoral endarterectomy during endovascular aortic aneurysm repair. Most of the patients had smoking history (84.2%), followed by hypertension (68.4%), dyslipidemia (63.2%), coronary heart disease (29.4%), and diabetes (26.3%). Only 3 patients (15.8%) were submitted exclusively to endarterectomy, 13 (68.4%) were submitted to endarterectomy as an adjuvant for peripheral endovascular treatment, 2 (10.5%) as a concomitant procedure to endovascular repair of aortic aneurysm, and 1 (5.3%) was complemented with thrombectomy of the femoro-popliteal sector. Primary patency rates were 100% and 87.5% (CI (38.7–98.1)) at 6 and 12 months, respectively. Primary-assisted and secondary patency rates were 100%. The 30-day mortality rate was 5.3% ( n = 1) and complication rate 10.5% ( n = 2). One patient complicated with acute renal disease related to rhabdomyolysis. Another patient developed a wound-related hematoma treated with surgical drainage, but died three days after consequent to ischemia-reperfusion injury. Conclusions Eversion femoral endarterectomy is a safe and feasible technique, with good patency results and respecting the concept of leaving nothing behind. A careful control of the proximal and distal endpoints is essential for the success of the technique.

Pectus excavatum is the most common deformity of the thorax. A minimally invasive surgical correction is commonly carried out to remodel the anterior chest wall by using an intrathoracic convex prosthesis in the substernal position. The process of prosthesis modeling and bending still remains an area of improvement. The authors developed a new system, i3DExcavatum, which can automatically model and bend the bar preoperatively based on a thoracic CT scan. This article presents a comparison between automatic and manual bending. The i3DExcavatum was used to personalize prostheses for 41 patients who underwent pectus excavatum surgical correction between 2007 and 2012. Regarding the anatomical variations, the soft-tissue thicknesses external to the ribs show that both symmetric and asymmetric patients always have asymmetric variations, by comparing the patients' sides. It highlighted that the prosthesis bar should be modeled according to each patient's rib positions and dimensions. The average differences between the skin and costal line curvature lengths were 84 ± 4 mm and 96 ± 11 mm, for male and female patients, respectively. On the other hand, the i3DExcavatum ensured a smooth curvature of the surgical prosthesis and was capable of predicting and simulating a virtual shape and size of the bar for asymmetric and symmetric patients. In conclusion, the i3DExcavatum allows preoperative personalization according to the thoracic morphology of each patient. It reduces surgery time and minimizes the margin error introduced by the manually bent bar, which only uses a template that copies the chest wall curvature.

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