Laparoscopic Extended Segmentectomy VIII Guided by Three-Dimensional Reconstruction and Hepatic Veins with a Cranio-Caudal Approach.

INTRODUCTION: Minimally invasive resection of segment VIII is a technically challenging procedure, made even more challenging when the resection is extended to segment IV and/or segment VII. Parenchymal-sparing resections are frequently used in the management of liver metastases but expose to the risk of R1 resection, especially with a minimally invasive approach. Preoperative surgical planning with 3D reconstruction and intraoperative guidance with hepatic vein is helpful for laparoscopic oncological liver resection.1-3 PATIENT AND METHODS: We present the case of a 58-year-old female with three metachronous liver metastases from epidermoid anal cancer. The disease was stable 6 months after cessation of chemotherapy. Metastases were mainly located in segment VIII (with a large segment VIII dorsal) but also in the territory of glissonian pedicles from segments IV and VII. Prior to surgery, three-dimensional (3D) reconstruction showed that a segmentectomy VIII would not be sufficient to have a safety margin and showed the relation between metastases and hepatic veins. Transection of the liver was performed with an ultrasonic dissector. Exposure of the hepatic veins was performed by gently pulling of the hepatic tissue from the vein, using the nonactive blade of the ultrasonic device. Activation of ultrasonic energy was performed only for sealing and dividing small collateral veins. Three transection lines were necessary. The posterior transection line, in segment VII, was determined with intraoperative ultrasound (IOUS), at 1 cm below the metastasis. The liver was transected superficially only. The medial transection line, in segment IV, was determined with IOUS, at 1 cm on the left of the metastasis, parallel to the middle hepatic vein. Finally, the inferior transection line, between segment V and segment VIII, was approximately determined with IOUS, vertically aligned with the hepatic vein of segment V. The transection line was further corrected after clamping the glissonian pedicle of segment VIII, according to fluorescence. The surgical procedure began with the mobilization of the right liver, including division of the hepato-caval ligament, followed by the superficial transection of the posterior margin in segment VII. Then, transection of segment IV was performed near the termination of the middle hepatic vein, which was further exposed with a cranio-caudal approach to minimize the risk of vein injury. The hepatic vein of segment V was then used as a landmark for the identification of the Glissonian pedicle of segment VIII, which was transected.4 Termination of the right hepatic vein (RHV) was then identified, and the ventral branch of the RHV was transected. The dorsal branch of the RHV was exposed with a cranio-caudal approach. Finally, transection of segment VII was performed toward the transection line made initially. RESULTS: Operative time was 360 min with 450 mL blood loss. The Pringle maneuver was used during 148 min. The patient was discharged on the seventh postoperative day. Pathological examination confirmed R0 resection, with 20-60% necrosis of the three liver metastases. The resected liver weight was 225 g. Six months after liver resection, the patient had a recurrence in a celiac lymph node, which was treated by radiotherapy. Fifteen months after liver resection, the patient is free of disease without active treatment. CONCLUSION: Preoperative virtual hepatectomy facilitates surgical planning by increasing the understanding of the tumors-vessels relationship. Intraoperative hepatic vein guidance with a cranio-caudal approach enables to follow preoperative surgical planning and to perform safe complex laparoscopic liver resection.

Targeted proteomics links virulence factor expression with clinical severity in staphylococcal pneumonia.

Introduction: The bacterial pathogen Staphylococcus aureus harbors numerous virulence factors that impact infection severity. Beyond virulence gene presence or absence, the expression level of virulence proteins is known to vary across S. aureus lineages and isolates. However, the impact of expression level on severity is poorly understood due to the lack of high-throughput quantification methods of virulence proteins. Methods: We present a targeted proteomic approach able to monitor 42 staphylococcal proteins in a single experiment. Using this approach, we compared the quantitative virulomes of 136 S. aureus isolates from a nationwide cohort of French patients with severe community-acquired staphylococcal pneumonia, all requiring intensive care. We used multivariable regression models adjusted for patient baseline health (Charlson comorbidity score) to identify the virulence factors whose in vitro expression level predicted pneumonia severity markers, namely leukopenia and hemoptysis, as well as patient survival. Results: We found that leukopenia was predicted by higher expression of HlgB, Nuc, and Tsst-1 and lower expression of BlaI and HlgC, while hemoptysis was predicted by higher expression of BlaZ and HlgB and lower expression of HlgC. Strikingly, mortality was independently predicted in a dose-dependent fashion by a single phage-encoded virulence factor, the Panton-Valentine leucocidin (PVL), both in logistic (OR 1.28; 95%CI[1.02;1.60]) and survival (HR 1.15; 95%CI[1.02;1.30]) regression models. Discussion: These findings demonstrate that the in vitro expression level of virulence factors can be correlated with infection severity using targeted proteomics, a method that may be adapted to other bacterial pathogens.

Quantification of infliximab and adalimumab in human plasma by a liquid chromatography tandem mass spectrometry kit and comparison with two ELISA methods.

Background: This study compared the performance of plasma infliximab and adalimumab quantification using a commercially available kit (mAbXmise kit) and mass spectrometry readout to that of two ELISA methods in patients treated for inflammatory bowel disease. Methods & results: The mAbXmise method based on liquid chromatography tandem mass spectrometry (LC-MS/MS) was linear from 2 to 100 µg/ml. It was validated according to international guidelines. Regarding cross-validation for infliximab (n = 70), the mean bias with LC-MS/MS assay was approximately threefold higher with the commercial ELISA assay compared with the in-house ELISA (-6.1 vs -1.8 µg/ml, respectively). The mean bias between the LC-MS/MS assay and in-house ELISA was -1.2 µg/ml for adalimumab (n = 35). Conclusion: The LC-MS/MS method is a powerful alternative to immunoassays to monitor concentrations of infliximab and adalimumab.

Multivariate curve resolution--alternating least squares applied to the investigation of ultrafast competitive photoreactions.

The main advantage of multivariate curve resolution - alternating least squares method (MCR-ALS) is the possibility to act as multiset analysis method, combining data coming from different experiments to provide a complete and more accurate description of a chemical system. Exploiting the multiset side, the combination of experiments obtained from two photo-active systems with complementary pathways and monitored by femtosecond UV-vis transient absorption spectroscopy is presented in this work. A multiset hard- and soft-multivariate curve resolution model (HS-MCR) was built allowing the description of the spectrokinetic features of the entire system. Additionally, reaction quantum yields were incorporated in the hard-model in order to describe branching ratios for intermediate species. The photodynamics of salicylidene aniline (SA) was investigated as a case study. The overall reaction scheme involves two competitive and parallel pathways. On the one hand, a photoinduced excited state intramolecular proton transfer (ESIPT) followed by a cis-trans isomerization leads to the so-called photochromic form of the molecule, which absorbs in the visible. The formation of the photochromic species is well characterized in the literature. On the other hand, a complex internal rotation of the molecule takes place, which is a competing reaction. The rotation mechanism is based on a trans-cis isomerization. This work aimed at providing a detailed spectrokinetic characterization of both reaction pathways for SA. For this purpose, the photodynamics of two molecules of identical parent structures and different substituent patterns were investigated in femtosecond transient absorption spectroscopy. For SA, the mechanism described above involving the two parallel pathways was observed, whereas for the derivative form of SA, the photochromic reaction was blocked because of the replacement of an H atom by a methyl group. The application of MCR approaches enabled to obtain transient spectra for the different intermediate species involved and rate constants for the photochromic reaction, thus contributing to a comprehensive description of the photodynamics of SA.

Baseline correction methods to deal with artifacts in femtosecond transient absorption spectroscopy.

In femtosecond transient absorption spectroscopy, artifact contributions are usually observed at ultra-short time scale. These complex signals are very challenging because of their nature, related to ultrafast phenomena, and because they strongly distort the structure of the spectrokinetic data. The purpose of this work is to evaluate the potential of baseline correction methods for femtosecond transient absorption spectroscopy data pre-processing. Indeed, artifacts removal should ideally be performed before multivariate data analysis. The work is thus mainly focused on two different approaches which are filtering by discrete wavelet transform, on the one hand, and smoothing by asymmetric least squares, on the other hand. The results obtained both on simulated data and on femtosecond pump-probe spectroscopy data are discussed. It can be concluded that asymmetric least squares smoothing procedure turns out to perform satisfactory for artifacts removal. Indeed, only mild discrepancies are observed in the transient spectra and, most important, good recovery of the kinetics is obtained at ultra-short time scale.

Investigation of ultrafast photoinduced processes for salicylidene aniline in solution and gas phase: toward a general photo-dynamical scheme.

Photodynamics of 2-hydroxybenzylideneaniline (photochromic salicylidene aniline SAOH) and N-(2-methoxybenzylidene)aniline (SAOMe) are studied by steady state and transient optical spectroscopy in solution and gas phase at different excitation wavelengths (266, 355 and 390 nm). Two competitive processes are observed from the enol* excited state: on one hand a rotation to get a twisted-enol, and on the other hand an excited state intramolecular proton transfer (ESIPT) followed by a cis-trans isomerisation to get the trans-keto photochromic product. For the first time both processes are characterized at an ultrashort time scale for salicylidene aniline. Resolution of the spectrokinetic data is achieved by multivariate curve resolution and attribution of the intermediate species recovered is performed in comparison with the results obtained for SAOMe, which can only undergo enol rotational isomerisation. It shows that ESIPT and rotation to the twisted-enol for SAOH occur within 100 fs, as predicted by recent quantum dynamical simulations, with an efficiency ratio dependent on the excitation wavelength. Therefore a general photoinduced mechanism for salicylidene aniline is drawn.