Study on the late effect of pneumonectomy on right heart pressures using Doppler echocardiography.

OBJECTIVE: Changes in the pulmonary artery systolic pressure (PASP) and the dimensions of the right ventricle (RV) of the heart, six months after pneumonectomy, were evaluated in order to detect the influence of pneumonectomy on right heart function. METHODS: 35 patients undergoing pneumonectomy (Group A) and 17 patients undergoing lobectomy or bilobectomy (Group B) were evaluated prospectively with spirometry, arterial blood gases determination and Doppler echocardiography at rest, preoperatively and six months postoperatively. Patients of both groups had normal preoperative PASP, RV dimensions and left ventricular ejection fraction. PASP was calculated using the equation: PASP=4x(maximal velocity of the tricuspid regurgitant jet)2+10 mmHg. FEV1, FVC, partial pressures of oxygen (pO2) and carbon dioxide in the arterial blood were considered as the main determinants of postoperative lung function. RESULTS: PASP increased significantly six months postoperatively in both groups (P<0.05). Mean PASP in Group A (40.51+/-12.52 mmHg) was significantly higher (P=0.012) than in Group B (32.88+/-5.25 mmHg). Mean PASP after right pneumonectomy (48.33+/-10.61 mmHg) was significantly higher (P=0.002) than after left pneumonectomy (35.26+/-10.83 mmHg). The incidence of RV dilatation was higher in Group A (60%) than in Group B (23.52%). RV dilatation was related with elevated PASP values in both groups (P<0.001 and P=0.034, respectively). Increased age (P<0.001), significant percent FVC reduction from preoperative values (P=0.012) and low pO2 values (P=0.001) were detected as strong predisposing factors for postpneumonectomy PASP elevation. CONCLUSIONS: Pneumonectomy is related with postoperative elevation of PASP and RV dilatation, especially right pneumonectomy. Significant percent FVC reduction, increased age and low pO2 values are the main responsible factors for elevation of the 6-month postoperative PASP values.     

Large-Volume Hyperthermia for Safe and Cost-Effective Targeted Drug Delivery Using a Clinical Ultrasound-Guided Focused Ultrasound Device

Lyso-thermosensitive liposomes (LTSLs) are specifically designed to release chemotherapy agents under conditions of mild hyperthermia. Preclinical studies have indicated that magnetic resonance (MR)-guided focused ultrasound (FUS) systems can generate well-controlled volumetric hyperthermia using real-time thermometry. However, high-throughput clinical translation of these approaches for drug delivery is challenging, not least because of the significant cost overhead of MR guidance and the much larger volumes that need to be heated clinically. Using an ultrasound-guided extracorporeal clinical FUS device (Chongqing HAIFU, JC200) with thermistors in a non-perfused ex vivo bovine liver tissue model with ribs, we present an optimised strategy for rapidly inducing (5–15 min) and sustaining (>30 min) mild hyperthermia (ΔT <+4°C) in large tissue volumes (≤92 cm³). We describe successful clinical translation in a first-in-human clinical trial of targeted drug delivery of LTSLs (TARDOX: a phase I study to investigate drug release from thermosensitive liposomes in liver tumours), in which targeted tumour hyperthermia resulted in localised chemo-ablation. The heating strategy is potentially applicable to other indications and ultrasound-guided FUS devices.     

A robust statistics-based global energy function for the alignment of serially acquired autoradiographic sections

Autoradiographic analysis of the functional changes occurring in the rat brain are most often performed on coronal sections that allow a good insight into the events occurring at the structural level but lacks the 3D context which is necessary to fully understand the involvement of the brain structures in specific situations like focal seizures with or without generalization. Therefore a robust, fully-automated algorithm for the registration of serially acquired autoradiographic sections is presented. The method accounts for the main difficulties of autoradiographic alignment: corrupted data (cuts and tears), dissimilarities or discontinuities between slices, non parallel or missing slices. The approach relies on the minimization of a global energy function based on robust statistics. The energy function measures the similarity between a slice and its neighborhood in the 3D volume. No particular direction is privileged in the method, so that global offsets, biases in the estimation or error propagations are avoided. The method is evaluated qualitatively and quantitatively on real autoradiographic data. Rat brain autoradiographic volumes are reconstructed with registration errors less than 1 degree in rotation and less than 1 pixel in translation.     

Abdominal metastases from lung cancer resulting in small bowel perforation: report of three cases

Metastatic lung cancer to the small bowel is a rare occurrence. Acute complications such as perforation, hemorrhage and obstruction are even rarer. We present 3 cases of small bowel perforation from metastatic lung cancer. All 3 patients underwent emergency laparotomy. In 2 of them there was no obvious macroscopic appearance of metastatic disease either at the site of perforation or in any other area of the abdomen, whereas in the third patient there were hepatic metastases. The postoperative period was uneventful in all three cases. The longest survival was four months. Our cases bring the number of cases reported in the international literature to a total of 43.     

Hemorrhagic lymphangioma mimicking hemoperitoneum: MR imaging diagnosis

Omental cystic lymphangioma is an uncommon malformation that occurs in children. The authors report the magnetic resonance (MR) imaging findings in a case of hemorrhagic cystic abdominal lymphangioma, which clinically mimicked a recurrent hemoperitoneum. They demonstrate the superiority of MR imaging relative to computed tomography and ultrasound in diagnosing large hemorrhagic cystic masses and differentiating them from free intraperitoneal fluid with multi-planar imaging and fluid characterization. This enables precise tumor localization and extension, aiding surgical resection.     

A potentially artifact-free oral contrast agent for gastrointestinal MRI

The combination of diamagnetic barium sulfate and superparamagnetic iron oxide (SPIO) in one suspension produces a macroscopic cancellation of positive and negative magnetic susceptibility components that can potentially eliminate susceptilbllity artifacts even with gradient echo pulse sequences. The relaxation properties that make the SPIO suspension a useful negative contrast agent are retained.     

Investigation of the Occurrence of Cyanotoxins in Lake Karaoun (Lebanon) by Mass Spectrometry,Bioassays and Molecular Methods

Lake Karaoun is the largest artificial lake in Lebanon and serves multiple purposes. Recently, intensive cyanobacterial blooms have been reported in the lake, raising safety and aesthetic concerns related to the presence of cyanotoxins and cyanobacterial taste and odor (T&O) compounds, respectively. Here, we communicate for the first time results from a recent investigation by LC-MS/MS covering multiple cyanotoxins (microcystins (MCs), anatoxin-a, cylindrospermopsin, nodularin) in water and fish collected between 2019 and 2020. Eleven MCs were identified reaching concentrations of 211 and 199 μg/L for MC-LR and MC-YR, respectively. Cylindrospermopsin, anatoxin-a and nodularin were not detected. The determination of the total MCs was also carried out by ELISA and Protein Phosphatase Inhibition Assay yielding comparable results. Molecular detection of cyanobacteria (16S rRNA) and biosynthetic genes of toxins were carried out by qPCR. Untargeted screening analysis by GC-MS showed the presence of T&O compounds, such as β-cyclocitral, β-ionone, nonanal and dimethylsulfides that contribute to unpleasant odors in water. The determination of volatile organic compounds (VOCs) showed the presence of anthropogenic pollutants, mostly dichloromethane and toluene. The findings are important to develop future monitoring schemes in order to assess the risks from cyanobacterial blooms with regard to the lake’s ecosystem and its uses.     

Solid MRI contrast agents for long-term,quantitative in vivo oxygen sensing

Targeted MRI contrast agents have proven useful in research and clinical studies for highlighting specific metabolites and biomarkers [Davies GL, et al. (2013) Chem Commun (Camb) 49(84):9704–9721] but their applicability in serial imaging is limited owing to a changing concentration postinjection. Solid enclosures have previously been used to keep the local concentration of contrast agent constant, but the need to surgically implant these devices limits their use [Daniel K, et al. (2009) Biosens Bioelectron 24(11):3252–3257]. This paper describes a novel class of contrast agent that comprises a responsive material for contrast generation and an injectable polymeric matrix for structural support. Using this principle, we have designed a contrast agent sensitive to oxygen, which is composed of dodecamethylpentasiloxane as the responsive material and polydimethylsiloxane as the matrix material. A rodent inspired-gas model demonstrated that these materials are functionally stable in vivo for at least 1 mo, which represents an order of magnitude improvement over an injection of liquid siloxane [Kodibagkar VD, et al. (2006) Magn Reson Med 55(4):743–748]. We also observed minimal adverse tissue reactions or migration of contrast agents from the initial injection site. This class of contrast agents, thus, represented a new and complementary method to monitor chronic diseases by MRI.MRI is one of the most important clinical technologies for monitoring disease progression and is unique among imaging modalities in its ability to gather both high-resolution anatomical images and physiological information in the same study (1). Targeted contrast agents are useful for highlighting specific molecules in the body (2), whereas responsive contrast agents enable quantitative diagnostics using MRI. The concentration of contrast agents decreases over time owing to systemic clearance (3); some magnetic resonance (MR) methods, such as dynamic contrast-enhanced imaging, exploit this clearance of contrast agent to make inferences about the underlying physiology. Some applications, however, require a consistent concentration of contrast agent for repeatable, accurate, and quantitative measurements (4), and an internal control must be added to account for the time-changing concentration. Repeat measurements to track the progression of disease or the response to treatment also require a new bolus injection of contrast agent. These additional injections introduce uncertainty in the measurements, and the safety of long-term exposure to the contrast agent must be investigated. We describe a novel solid contrast agent that eliminates these issues to enable longitudinal imaging sensitive to oxygen. It consists of a contrast agent embedded in an injectable polymeric matrix where the matrix ensures the retention of sensitive agents in the target tissue for extended periods of time. We believe that these agents will find use in clinical medicine by enabling quantitative measurements of specific local metabolites in chronic conditions.One area where longitudinal imaging can affect clinical decision making is sensing of local oxygen tension. Oxygen plays an important role in many pathological processes, such as cancer (5), peripheral vascular disease (6), and wound healing (7). Oxygen delivery in cancer can be limited transiently by perfusion interruption or chronically by increases in diffusion distance (8); both of these mechanisms result in hypoxia. Hypoxia in cancer confers resistance to radiotherapy (9, 10), impedes the action of chemotherapeutic agents (11), and promotes metastasis (12). Recent studies have attributed the low efficacy of drugs designed to target hypoxia to the lack of a suitable companion diagnostic assay (13–15). A diagnostic assay for selecting appropriate patients for hypoxia-targeted treatment or doses for radiotherapy would need to report oxygen status in the tumor at multiple time points during the course of treatment, because the tumor oxygen tension is dynamic and changes in response to treatment (16). There is a need for an oxygen assay that can provide oxygen information in the same location so that follow-up data can be used to evaluate treatment efficacy. Earlier attempts to measure oxygen with polarographic needle oxygen electrodes provided important evidence of hypoxia in human tumors, but oxygen electrodes have limited clinical applications owing to the invasiveness of the measurement procedure (17). Technologies currently used in the clinic for monitoring oxygen are only useful in areas with sufficient blood flow [pulse oximetry (18)], that are close to the surface [transcutaneous oximetry (19)], or that have limited changes in oxygen tension [fiber optic probes (15)]. Magnetic resonance methods, such as electron paramagnetic resonance (20) and ¹⁹F oximetry (21), provide direct measurement of local oxygen tension but require specialized equipment not currently present in most medical centers. Other MR technologies, such as blood-oxygen-level-dependent and tissue-oxygen-level-dependent contrast imaging, are qualitative in nature and do not report absolute tissue oxygen tension (15, 22).MRI contrast agents are compatible with existing equipment in the clinic, but the clearance of the contrast agent prohibits long-term monitoring. Several technologies have previously been developed to compensate for variations in contrast agent concentration (23). These methods typically require measurement of multiple parameters or established perfusion models to compensate for the concentration changes (24). Our matrix-embedded contrast agent performs measurements independently of perfusion, is not cleared, and shows no loss in performance after 1 mo in vivo.