- Cardio-pulmonary MRI for detection of treatment response after a single BPA treatment session in CTEPH patients. [Journal Article]
- EREur Radiol 2018 Oct 11
- CONCLUSIONS: Cardio-pulmonary MRI detects and quantifies treatment response after a single BPA treatment session.• Two months after BPA regional parenchymal pulmonary perfusion (PBF) increased in the total lung parenchyma (p = 0.005), the treated lobes (p < 0.0001) and non-treated lobes (p = 0.015). • The PBF treatment changes in the treated lobe were significantly larger than in the non-treated lobes (p = 0.0049). • Change in NT proBNP, MRI-derived mean pulmonary artery pressure, pulmonary transit time, full width at half maximum, right ventricular (RV) ejection fraction, RV stroke volume, cardiac output, ventricular mass index and PBF in the non-treated lobes correlated with PBF change in the treated lobe (p < 0.05).
- Chronic In Vivo Test of a Right Heart Replacement Blood Pump for Failed Fontan Circulation. [Journal Article]
- AJASAIO J 2018 Oct 03
- An implantable rotary blood pump was developed to provide long-term mechanical right heart support for patients who have failing Fontan circulation. The objective of this study was to evaluate the pu...
An implantable rotary blood pump was developed to provide long-term mechanical right heart support for patients who have failing Fontan circulation. The objective of this study was to evaluate the pump in vivo in a 30 day sheep study. Pump speed was set at 3,900 rpm for the duration of the study, and pump power was between 4.3 and 4.6 W. The pump inlet pressures for the superior vena cava (SVC) and inferior vena cava (IVC) were 14 ± 15 and 11 ± 15 mm Hg, respectively, over the duration of the study. Hematocrit remained stable at 30% ± 4%. Partial thromboplastin time (PTT) steadily increased from 30 s preoperatively to a high of 59 s on postoperative day 20, while prothrombin time (PT) remained at 20 ± 2 s for the duration of the study. The implantation and postoperative recovery were successful, and the animal demonstrated normal physiologic pulmonary and venous pressures and cardiac output. On pump inspection, the IVC and SVC inlets were completely clear of any deposits, but there were small thrombi (approximately 0.5 mm diameter) between each of the three rotor blades and along 20% of the parting line of the two volute halves. A complete right heart bypass was performed, postoperative recovery was successful, and the pump demonstrated adequate circulatory support and normal physiologic pulmonary and venous pressures. This study was the first successful test of a right heart replacement device in a chronic animal study.
- Postoperative bridging anticoagulation and left ventricular assist system thrombosis. [Journal Article]
- JTJ Thromb Thrombolysis 2018 Sep 25
- Reduced emphasis on early postoperative bridging anticoagulation is one explanation for the increased incidence of HeartMate II (HM II) pump thrombosis. We conducted a single-center analysis of initi...
Reduced emphasis on early postoperative bridging anticoagulation is one explanation for the increased incidence of HeartMate II (HM II) pump thrombosis. We conducted a single-center analysis of initial postoperative anticoagulation practices and their impact on the incidence of HM II pump thrombosis. Data was collected on 105 patients undergoing primary HM II implant from 2009 to 2014. A parenteral bridge was defined as use of parenteral anticoagulation prior to attainment of an international normalized ratio ≥ 2 on warfarin. A parenteral bridge was further characterized as early if initiated ≤ 3 days of implant and therapeutic if a manufacturer-specified goal partial thromboplastin time (PTT) was achieved during each of the first 3 days of administration. Pump thrombosis was "suspected" based upon suggestive clinical parameters leading to hospital admission with parenteral anticoagulant administration and "confirmed" by direct visualization of thrombus in the device. A majority of patients (70%) were treated with an initial parenteral bridge, which was started within 3 days of device implantation in 68% of cases. Therapeutic PTT levels were achieved in 52% of patients treated with a parenteral bridge. Patients who were bridged had lower Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles (p = 0.039) and longer intensive care unit stay (p = 0.005). Pump thrombosis was suspected in 25% and confirmed in 13% of patients within 6 months of implant. Point estimates of pump thrombosis incidence demonstrated a lower event rate at 6 months in patients who received a therapeutic bridge (15.8%, 95% CI 6.3-29.1% for suspected; 7.9%, 95% CI 2.0-19.3% for confirmed) compared to those who did not receive a therapeutic bridge (29.9%, CI 19.3-41.1% for suspected; 16.4%, 95% CI 8.7-26.3% for confirmed). This trend was not sustained at 12 and 24 months. Cumulative incidence analyses showed no significant difference in the overall incidence of pump thrombosis between patients who did and did not receive a parenteral bridge. In patients undergoing HM II implantation, the use of initial postoperative parenteral bridging anticoagulation is common but frequently sub-therapeutic. Use of a parenteral bridge reaching therapeutic targets may decrease the 6-month but not the overall incidence of pump thrombosis.
- Modulating Hypoxia via Nanomaterials Chemistry for Efficient Treatment of Solid Tumors. [Journal Article]
- ACAcc Chem Res 2018 Sep 20
- The common existence of hypoxia in solid tumors has been heavily researched because it renders tumors more resistant to most standard therapeutic methods, such as radiotherapy (RT), chemotherapy, and...
The common existence of hypoxia in solid tumors has been heavily researched because it renders tumors more resistant to most standard therapeutic methods, such as radiotherapy (RT), chemotherapy, and photodynamic therapy (PDT), and is associated with a more malignant phenotype and poor survival in patients with tumors. The development of hypoxia modulation methods for advanced therapeutic activity is therefore of great interest but remains a considerable challenge. Since the significant development of nanotechnology and nanomedicine, functionalized nanomaterials can be exploited as adjuvant "drugs" for these oxygen-dependent standard therapies or as hypoxia initiators for advanced new therapies to solid tumors. In this Account, we summarize our recent studies on the design and synthesis of nanomaterials with a set of desired chemistry benefits achievable by modulating hypoxia, suggesting a valid therapeutic option for tumors. The investigated strategies can be categorized into three groups: The first strategy is based on countering hypoxia. Considering that O2 deficiency is the major obstacle for the oxygen-dependent therapies, we initially developed methods to supply O2 by taking advantage of the hypoxia-responsive properties of nano-MnO2 or nanomaterials' photothermal effects for increased intratumoral blood flow. The second approach is to disregard hypoxia. Possible benefits of nanoagents include reducing/eliminating reliance on O2 or making O2 replacements as adjuvants to standard therapies. To this end, we investigated a nano-upconversion/scintillator with the capacity toup-/down-convert near-infrared light (NIR)/X-ray to luminescence in the ultraviolet/visible region fortype-I PDT with minimized oxygen-tension dependency or developed Fe-based nanomaterials for chemodynamic therapy (CDT) without external energy and oxygen participation for efficient free radical killing of deep tumors. The third strategy involves exploiting hypoxia. The unique biological characteristics of hypoxia are exploited to activate nanoagents for new therapies. To address the discrepancy between the nanoagents' demand and supply within the hypoxia region, a smart "molecule-nano" medicine that stays small-molecule-like in the bloodstream and turns into self-assembled nanovesicles after entry into the hypoxia region was constructed for hypoxia-adaptive photothermal therapy (PTT). In addition to traditional anti-angiogenesis therapy, we prepared Mg2Si nanoparticles by a special self-propagating high-temperature synthesis approach. These nanoparticles can directly remove the intratumoral oxygen via the oxidation reactions of Mg2Si and later efficiently block the rapid reoxygenation via tumor blood vessels by the resultant SiO2 microsheets for cancer starvation therapy. Taken together, these findings indicate that nanomaterials will assume a valuable role for anticancer exploration based on either their properties to make up oxygen deficiency or the use of hypoxia for therapeutic applications.
- Platelet-mimicking nanoparticles co-loaded with W18O49 and metformin alleviate tumor hypoxia for enhanced photodynamic therapy and photothermal therapy. [Journal Article]
- ABActa Biomater 2018 Sep 15
- W18O49-mediated photodynamic therapy (PDT) and photothermal therapy (PTT) are limited by the easily oxidized property and tumor hypoxia. Here, we report the development of platelet membranes as nanoc...
W18O49-mediated photodynamic therapy (PDT) and photothermal therapy (PTT) are limited by the easily oxidized property and tumor hypoxia. Here, we report the development of platelet membranes as nanocarriers to co-load W18O49 nanoparticles (NPs) and metformin (PM-W18O49-Met NPs). Platelet membranes can protect W18O49 from oxidation and immune evasion, and increase the accumulation of W18O49 in tumor sites via the passive EPR effect and active adhesion between platelets and cancer cells. The introduction of metformin (Met), a typical anti-diabetic drug, can alleviate the tumor hypoxia through reducing oxygen consumption. As a result, ROS and heat generation are both greatly increased, as revealed by ROS/hypoxia imaging in vitro, IR thermal imaging in vivo and PET imaging in vivo. PM-W18O49-Met NPs show the improved therapeutic effects with greatly inhibited tumor growth and induced tumor cell apoptosis. Therefore, our work provides a novel strategy for simultaneous enhanced PDT and PTT, which is promising in bioapplication.
- CuS@MOF-Based Well-Designed Quercetin Delivery System for Chemo-Photothermal Therapy. [Journal Article]
- AAACS Appl Mater Interfaces 2018 Sep 26
- Quercetin (QT) is one promising candidate for the treatment of various cancers with virtually no toxic side effects. However, its anticancer effect is severely restricted by its poor bioavailability,...
Quercetin (QT) is one promising candidate for the treatment of various cancers with virtually no toxic side effects. However, its anticancer effect is severely restricted by its poor bioavailability, low water solubility, and chemical instability in the neutral and alkaline medium. Herein, zeolitic imidazolate framework-8 (ZIF-8) is first reported as the multifunctional nanoplatform to the codelivery of quercetin as an anticancer agent and CuS nanoparticles as a photothermal therapy (PTT) agent for synergistic combination of chemotherapy and PTT as well as overcoming the drawbacks of quercetin. Moreover, folic acid-bovine serum albumin (FA-BSA) conjugates are applied to stabilize the CuS@ZIF-8-QT to promote the bioavailability of quercetin and realize active-targeting drug delivery. Near-infrared (NIR) fluorescent imaging demonstrated the highly increased drug accumulations of FA-BSA/CuS@ZIF-8-QT in tumors, resulting from efficient internalization via FA-receptors-mediated endocytosis. The results of in vivo and in vitro anticancer experiments demonstrate that quercetin and PTT agent can work together efficiently under NIR irradiation, thus remarkably improving the anticancer effect. Therefore, our newly designed FA-BSA/CuS@ZIF-8-QT multifunctional drug delivery system might be a promising nanoplatform for cancer treatment.
- Eicosanoid mediation of immune responses at early bacterial infection stage and its inhibition by Photorhabdus temperata subsp. temperata, an entomopathogenic bacterium. [Journal Article]
- AIArch Insect Biochem Physiol 2018 Aug 17; :e21502
- An entomopathogenic bacterium Photorhabdus temperata subsp. temperata (Ptt) infects insect hemocoel by the vectoring activity of its symbiotic nematode, Heterorhabditis megidis. The bacterium induces...
An entomopathogenic bacterium Photorhabdus temperata subsp. temperata (Ptt) infects insect hemocoel by the vectoring activity of its symbiotic nematode, Heterorhabditis megidis. The bacterium induces host immunosuppression by inhibiting eicosanoid biosynthesis. This study investigated the role of eicosanoids in immune responses of the beet armyworm, Spodoptera exigua, in the early bacterial infection stage (first 3 hr postinfection [PI]). After infection with the nonpathogenic Escherichia coli (Ec), the bacterium maintained its population for the first 3 hr PI, then rapidly decreased in numbers. During the 3 hr PI of Ptt, this pathogenic bacterium also did not show any significant change in bacterial population. However, Ptt rapidly increased its population size after the initial lag phase, inducing fatal septicemia. This study further analyzed cellular and humoral immune responses of the beet armyworm during the initial 3 hr PI. During this early stage, challenge with Ec stimulated hemocyte-spreading behavior along with extensive F-actin growth. However, Ptt infection suppressed hemocyte spreading. Expression levels of three antimicrobial peptides (lysozyme, gloverin, and gallerimycin) were significantly inhibited during Ptt infection. Phospholipase A2 activity was significantly induced during the early infection stage of Ec, but not during Ptt infection. Addition of eicosanoid biosynthesis inhibitors significantly reversed the initial immunosuppression. These results suggest that, during the early infection stage, Ptt can shutdown eicosanoid biosynthesis which can prevent acute immune responses of host insects.
- Posterior laxity increases over time after PCL reconstruction. [Journal Article]
- KSKnee Surg Sports Traumatol Arthrosc 2018 Jul 02
- CONCLUSIONS: Early results after PCL reconstruction seem promising as posterior tibial translation is significantly improved. However, there is a significant increase in PTT from early postoperative values to the final follow-up of at least 5 years. This is particularly notable in patients with flattening of the TS. As a consequence, surgeons and patients need to be aware that initial posterior stability should not be equated with the final outcome.
- Changes in Hyolaryngeal Movement During Swallowing in the Lateral Decubitus Posture. [Journal Article]
- ARAnn Rehabil Med 2018 Jun 27; 42(3):416-424
- CONCLUSIONS: The results showed that the peak and initial positions of the hyoid and larynx and the pattern of hyoid movement varied significantly depending on the body postures. This study suggests that the LD posture was one of the safe feeding postures without any increased risk compared with UP posture.
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- Effects of repeated conditioning pain modulation in healthy volunteers. [Journal Article]
- EJEur J Pain 2018 Jun 29
- CONCLUSIONS: Conditioned pain modulation-effects were maintained over four consecutive bouts and in the control-session repeated pain thresholds assessments habituated more than in the CPM-session leading to an increase in netCPM-effect over the four bouts.Conditioning pain modulation can be assessed in 5-min intervals by cuff algometry with a fixed conditioning stimulus. Without applying conditioning stimuli the pain sensitivity of test-stimuli habituated. As a consequence, it can be speculated that the conditioning stimulus may negate the temporal habituation effects during repeated sessions, whereas this may not be the case for unconditioned stimuli. Applying both conditioned and unconditioned repeated test-stimuli may be a way to assess different parts of the pain modulatory system, and a model for measuring a netCPM-effect, which could indicate a balance between habituation and sensitization, is proposed.