Treatment of Pulmonary Sequestrations by Means of Endovascular Embolization: Future or Fashion?

Bronchopulmonary sequestration is a rare malformation of the lower respiratory tract. Several methods of treatment have been described since the first publication. We present two cases of female adult patients with bronchopulmonary sequestration. In the first patient an unsuccessful attempt to treat the bronchopulmonary sequestration by means of arterial embolization is described. She was subsequently treated by means of surgical resection, which was the primary treatment for the second patient. Although endovascular techniques are becoming promising, in our opinion surgical resection remains the unique treatment for bronchopulmonary sequestration

A synbiotic mixture of Bifidobacterium breve M16-V, oligosaccharides and pectin, enhances Short Chain Fatty Acid production and improves lung health in a preclinical model for pulmonary neutrophilia

IntroductionPulmonary neutrophilia is a hallmark of numerous airway diseases including Chronic Obstructive Pulmonary Disease (COPD), Neutrophilic asthma, Acute Lung Injury (ALI), Acute Respiratory Distress Syndrome (ARDS) and COVID-19. The aim of the current study was to investigate the effect of dietary interventions on lung health in context of pulmonary neutrophilia.MethodsMale BALB/cByJ mice received 7 intra-nasal doses of either a vehicle or lipopolysaccharides (LPS). To study the effect of nutritional interventions they received 16 intra-gastric doses of either a vehicle (PBS) or the following supplements (1) probiotic Bifidobacterium breve (B. breve) M16-V; (2) a prebiotic fiber mixture of short-chain galacto-oligosaccharides, long-chain fructo-oligosaccharides, and low-viscosity pectin in a 9:1:2 ratio (scGOS/lcFOS/lvPectin); and (3) A synbiotic combination B. breve M16-V and scGOS/lcFOS/lvPectin. Parameters for lung health included lung function, lung morphology and lung inflammation. Parameters for systemic immunomodulation included levels of fecal short chain fatty acids and regulatory T cells.ResultsThe synbiotic supplement protected against the LPS induced decline in lung function (35% improved lung resistance at baseline p = 0.0002 and 25% at peak challenge, p = 0.0002), provided a significant relief from pulmonary neutrophilia (40.7% less neutrophils, p < 0.01) and improved the pulmonary neutrophil-to-lymphocyte ratio (NLR) by 55.3% (p = 0.0033). Supplements did not impact lung morphology in this specific experiment. LPS applied to the upper airways induced less fecal SCFAs production compared to mice that received PBS. The production of acetic acid between day −5 and day 16 was increased in all unchallenged mice (PBS-PBS p = 0.0003; PBS-Pro p < 0.0001; PBS-Pre, p = 0.0045; PBS-Syn, p = 0.0005) which upon LPS challenge was only observed in mice that received the synbiotic mixture of B. breve M16-V and GOS:FOS:lvPectin (p = 0.0003). A moderate correlation was found for butyric acid and lung function parameters and a weak correlation was found between acetic acid, butyric acid and propionic acid concentrations and NLR.ConclusionThis study suggests bidirectional gut lung cross-talk in a mouse model for pulmonary neutrophilia. Neutrophilic lung inflammation coexisted with attenuated levels of fecal SCFA. The beneficial effects of the synbiotic mixture of B. breve M16-V and GOS:FOS:lvPectin on lung health associated with enhanced levels of SCFAs

The novel gene asb11:a regulator of the size of the neural progenitor compartment

From a differential display designed to isolate genes that are down-regulated upon differentiation of the central nervous system in Danio rerio embryos, we isolated d-asb11 (ankyrin repeat and suppressor of cytokine signaling box–containing protein 11). Knockdown of the d-Asb11 protein altered the expression of neural precursor genes sox2 and sox3 and resulted in an initial relative increase in proneural cell numbers. This was reflected by neurogenin1 expansion followed by premature neuronal differentiation, as demonstrated by HuC labeling and resulting in reduced size of the definitive neuronal compartment. Forced misexpression of d-asb11 was capable of ectopically inducing sox2 while it diminished or entirely abolished neurogenesis. Overexpression of d-Asb11 in both a pluripotent and a neural-committed progenitor cell line resulted in the stimulus-induced inhibition of terminal neuronal differentiation and enhanced proliferation. We conclude that d-Asb11 is a novel regulator of the neuronal progenitor compartment size by maintaining the neural precursors in the proliferating undifferentiated state possibly through the control of SoxB1 transcription factors

Protein-Tyrosine Kinase Activity Profiling in Knock Down Zebrafish Embryos

BACKGROUND: Protein-tyrosine kinases (PTKs) regulate virtually all biological processes. PTKs phosphorylate substrates in a sequence-specific manner and relatively short peptide sequences determine selectivity. Here, we developed new technology to determine PTK activity profiles using peptide arrays. The zebrafish is an excellent model system to investigate signaling in the whole organism, given its wealth of genetic tools, including morpholino-mediated knock down technology. We used zebrafish embryo lysates to determine PTK activity profiles, thus providing the unique opportunity to directly compare the effect of protein knock downs on PTK activity profiles on the one hand and phenotypic changes on the other. METHODOLOGY: We used multiplex arrays of 144 distinct peptides, spotted on a porous substrate, allowing the sample to be pumped up and down, optimizing reaction kinetics. Kinase reactions were performed using complex zebrafish embryo lysates or purified kinases. Peptide phosphorylation was detected by fluorescent anti-phosphotyrosine antibody binding and the porous chips allowed semi-continuous recording of the signal. We used morpholinos to knock down protein expression in the zebrafish embryos and subsequently, we determined the effects on the PTK activity profiles. RESULTS AND CONCLUSION: Reproducible PTK activity profiles were derived from one-day-old zebrafiish embryos. Morpholino-mediated knock downs of the Src family kinases, Fyn and Yes, induced characteristic phenotypes and distinct changes in the PTK activity profiles. Interestingly, the peptide substrates that were less phosphorylated upon Fyn and Yes knock down were preferential substrates of purified Fyn and Yes. Previously, we demonstrated that Wnt11 knock down phenocopied Fyn/Yes knock down. Interestingly, Wnt11 knock down induced similar changes in the PTK activity profile as Fyn/Yes knock down. The control Nacre/Mitfa knock down did not affect the PTK activity profile significantly. Our results indicate that the novel peptide chip technology can be used to unravel kinase signaling pathways in vivo

Robotics in vascular surgery: Current status and potentials

While endoscopic surgery has rapidly made headway among various specialties, vascular surgeons worldwide still seem uncomfortable surrendering to this minimally invasive technique. Despite a small number of impressive series of laparoscopy-assisted and totally laparoscopic aortic treatments, the technical challenge of this approach seems to prevent vascular surgeons from frequently practicing this technique. This explanation might be due to the fact that the laparoscopic approach of the (abdominal) aorta and the laparoscopic creation of an aortic anastomosis is a serious technical challenge that demands a great deal of practice and experience before it can be applied in a clinical setting

Suture damage during robot-assisted vascular surgery: Is it an issue?

BACKGROUND: Manipulation of sutures during endoscopic surgery could lead to damage of suture structure, supposedly resulting in loss of strength. Lack of tactile feedback in robotic surgical systems might increase this problem. The objective of this study is to evaluate suture strength after robotic manipulation and to determine which suture material is least susceptible to damage from robotic manipulation. METHODS: The da Vinci surgical system was used to manipulate sutures. Three different suture materials (Prolene, ePTFE, Ethibond) of 3 different sizes (3-0, 4-0, and 5-0) were tested. A total of 270 sutures were pulled on a Servohydraulic Universal Testing Machine. The frequency of breaks at a manipulation-point and the maximum applied force (N) before the suture broke were used for statistic analysis. RESULTS: No loss in strength was shown in the ePTFE sutures after manipulation, whereas both Prolene and Ethibond sutures showed a significant loss of strength. CONCLUSIONS: ePTFE sutures are least susceptible to robotic manipulations and are, therefore, to be considered as a material of first choice

Carotid stent mobility with regard to head movements: In vitro analysis

Given that considerable motion of the carotid artery is present during head movements, we hypothesized that a flexible stent with low torsion might be favorable to avoid stress imparted to the stent and carotid artery. Therefore, we evaluated the flexibility of different expanded carotid stents before and after deployment in a carotid artery in vitro. Subsequently, we evaluated torsion of the bare expanded stents. Five stents (Wallstent [Boston Scientific Corp., Natick, MA], Acculink [Guidant Corp., Indianapolis, IN], Precise [Cordis Corp., Johnson & Johnson Company, Warren, NJ], Carotid SE [Medtronic AVE, Santa Rosa, CA], and Protégé [EV3, Plymouth, MN]) were tested. Flexibility was determined using a three-point bend test recording the bending load (BL) in grams required to flex the stent 25°. Increased BL implies decreased flexibility. Torsion was measured by recording the rotation load (RL) in grams required to rotate the stents 30° along its axis. Increased RL implies increased torsion. In the bare expanded state, the median BL was 6 g (range 1-22 g). The BL increased to 38 g (range 20-41 g) after deployment in a carotid artery, with the Carotid SE (21 g) and Wallstent (36 g) showing significantly lower BL (p < .0001 and p = .0016, respectively). Overall, the RL was 11 g (range 1-76 g). Significantly higher RL was required to rotate the Wallstent (73 g) and Precise (20 g) stents (p < .0001). The flexibility of the currently used stents decreases after deployment in a carotid artery irrespective of its flexibility in the bare state. Two stents showed increased torsion compared with the other stents. Limitations in both flexibility and torsion might influence the long-term performance of carotid angioplasty stenting

Modular branched endograft system for aortic aneurysm repair: Evaluation in a human cadaver circulation model

A circulation model was created in 6 nonaneurysmal human cadavers to evaluate the deliverability, deployment, and acute performance of a modular branched endograft system for treatment of aortic aneurysms containing essential branch vessels. Two fenestrations were created in an appropriately sized aortic main endograft. Under fluoroscopic guidance, the main endograft was advanced to the target site and the fenestrations were aligned with the ostia of the renal arteries. Branch grafts were placed through the fenestrations into the renal arteries. The outcome was evaluated by post implant angiography and autopsy. Eleven branch grafts were deployed at the target site. All targeted renal arteries showed good patency. At autopsy, all main endografts were adequately deployed, and 10 of 11 branch grafts were locked in place. In this model, deliverability and deployment of the modular branch graft system is feasible in a reliable, predictable, and timely fashion