A metaanalysis of the effectiveness and safety of ozone treatments for herniated lumbar discs.
J Vasc Interv Radiol. 2010 Apr;21(4):534-48. Epub 2010 Feb 25. PMID: 20188591
Jim Steppan, Thomas Meaders, Mario Muto, Kieran J Murphy
ActiveO, Salt Lake City, Utah, USA.
PURPOSE: To determine statistically significant effects of oxygen/ozone treatment of herniated discs with respect to pain, function, and complication rate. MATERIALS AND METHODS: Random-effects metaanalyses were used to estimate outcomes for oxygen/ozone treatment of herniated discs. A literature search provided relevant studies that were weighted by a study quality score. Separate metaanalyses were performed for visual analog scale (VAS), Oswestry Disability Index (ODI), and modified MacNab outcome scales, as well as for complication rate. Institutional review board approval was not required for this retrospective analysis. RESULTS: Twelve studies were included in the metaanalyses. The inclusion/exclusion criteria, patient demographics, clinical trial rankings, treatment procedures, outcome measures, and complications are summarized. Metaanalyses were performed on the oxygen/ozone treatment results for almost 8,000 patients from multiple centers. The mean improvement was 3.9 for VAS and 25.7 for ODI. The likelihood of showing improvement on the modified MacNab scale was 79.7%. The means for the VAS and ODI outcomes are well above the minimum clinically important difference and the minimum (significant) detectable change. The likelihood of complications was 0.064%. CONCLUSIONS: Oxygen/ozone treatment of herniated discs is an effective and extremely safe procedure. The estimated improvement in pain and function is impressive in view of the broad inclusion criteria, which included patients ranging in age from 13 to 94 years with all types of disc herniations. Pain and function outcomes are similar to the outcomes for lumbar discs treated with surgical discectomy, but the complication rate is much lower (<0.1%) and the recovery time is significantly shorter.
Article Published Date : Apr 01, 2010
[Hyper- or normobaric oxygen therapy to treat migraine and cluster headache pain. Cochrane review].
Schmerz. 2008 Apr;22(2):129-32, 134-6. PMID: 17885769
A Schnabel, M Bennet, F Schuster, N Roewer, P Kranke
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Münster, Münster, Germany.
BACKGROUND: The aim of this systematic review was to assess the benefits and harms of supplemental oxygen (HBOT/NBOT) for treating and preventing migraine and cluster headaches.
MATERIAL AND METHODS: All randomized trials comparing the effect of supplemental oxygen on migraine or cluster headache with those that exclude supplemental oxygen were included in this review. The systematic search included all relevant sources according to the paradigms of the Cochrane Collaboration. Data were analyzed with RevMan 4.2.
RESULTS: Nine trials involving 201 participants satisfied the inclusion criteria. HBOT was effective in relieving an acute migraine and seemed to be sufficient in the treatment of an acute cluster attack. NBOT was effective in terminating acute cluster headache compared to sham treatment, but not in comparison to sublingual ergotamine. There was no evidence for any prophylactic effects. Serious adverse effects were not noted in the trials investigated.
CONCLUSIONS: There is some evidence that HBOT is effective for termination of acute migraine. NBOT was similarly effective in cluster headache, however with sparse data. Because of costs and poor availability HBOT cannot be regarded as a routine therapy. Further indications in the case of treatment failure using standard therapy need to be defined based on data of future clinical trials.
Article Published Date : Apr 01, 2008
Two cases of hepatopulmonary syndrome with improved liver function following long-term oxygen therapy.
J Gastroenterol. 2007 Feb;42(2):176-80. Epub 2007 Mar 12. PMID: 17351808
Kazuko Y Fukushima, Hiroshi Yatsuhashi, Akitoshi Kinoshita, Toshihito Ueki, Takehiro Matsumoto, Mitsuhiko Osumi, Yohjiro Matsuoka
Hepatopulmonary syndrome (HPS) is a complication of liver disease that is characterized by hypoxemia and intrapulmonary vascular dilatations. The only established therapy for this disorder is liver transplantation. Here, we report two patients (a 63-year-old woman and a 72-year-old man) with HPS associated with hepatitis C virus-related cirrhosis. We gave the patients low-dose oxygen supplementation to improve their respiratory symptoms. Surprisingly, their liver function improved from Child Pugh class C to class A, and ascites disappeared after a year of oxygen supplementation. We believe that long-term oxygen therapy contributed to the improvement of liver function in these two cases. Long-term oxygen therapy might offer a new therapeutic approach to improve liver function in patients with cirrhosis with hypoxemia.
Article Published Date : Feb 01, 2007
Prevalence and Factors Contributing to Daytime and Nocturnal Hypoxemia in Chronic Heart Failure Patients.
Respiration. 2019 Jan 17;:1-10
Authors: Tamisier R, Bocquillon V, Treptow E, Destors M, Salvat M, Borrel E, Pépin JL
BACKGROUND: Despite clinical optimization, many chronic heart failure (CHF) patients remain symptomatic with dyspnea and poor quality of life.
STUDY OBJECTIVE: While oxygen therapy is prescribed in severe cases, the actual prevalence of different patterns of hypoxemia is unknown.
METHODS: We analyzed 183 stable CHF patients with optimized medical treatment in the "MARS" database. The patients underwent cardiorespiratory sleep recording and complete daytime pulmonary function tests including arterial blood gases.
RESULTS: This prospective cohort was predominately male (86.3%) with a mean age of 67.3 years (59.3; 75.7) and a mean BMI of 26.7 kg/m2 (23.7; 31.1). The patients were mainly in NYHA classes II and III with a mean left ventricular ejection fraction of 38%. 102 (55.61%) patients had ischemic cardiomyopathy with multiple comorbidities, and 64 (35.06%) had airflow obstruction. 8 (4.37%) patients had hypoxemia both day and night, and 151 (82.5%) had nocturnal hypoxemia only. All but 3 patients had sleep-disordered breathing (SDB), and either obstructive (59%) or central sleep apnea (39%) with a mean apnea-hypopnea index of 29.59/h (16.48; 48.27), an oxygen desaturation index of 27.09/h (14.09; 45.25), time below 90% saturation of 18 min (2; 64), and a mean nocturnal saturation of 93% (92; 94). Univariate analysis found nocturnal hypoxemia was associated with higher BMI and NT-proBNP levels. In multivariate analysis, only sleep apnea severity (p < 0.0001) and diurnal PaO2 remained significant.
CONCLUSION: Most stable CHF patients suffer from nocturnal hypoxemia, while daytime hypoxemia is relatively rare. The degree of nocturnal hypoxemia depends on the severity of SDB. Hypoxemia phenotyping and severity could help better evaluate the need for appropriate therapy in CHF patients.
PMID: 30654381 [PubMed - as supplied by publisher]
PEGylated mesoporous Bi2S3 Nanostars loaded with Chlorin e6 and doxorubicin for fluorescence/CT imaging-guided multimodal therapy of Cancer.
Nanomedicine. 2019 Jan 14;:
Authors: Sun L, Hou M, Zhang L, Qian D, Yang Q, Xu Z, Kang Y, Xue P
Taking advantage of the mesoporous structure of bismuth sulfide nanostars (Bi2S3 NSs), a chemotherapeutic drug of doxorubicin (DOX) and a photosensitizer of chlorin e6 (Ce6) were concurrently loaded in the PEGylated Bi2S3 NSs to formulate a multifunctional nanocomplex (BPDC NSs) for tumor theranostics. BPDC NSs have excellent photothermal conversion efficiency and a capacity of yielding reactive oxygen species (ROS) upon laser irradiation, and can realize on-demand drug release by either pH-activation or thermal induction. Accumulation of the nanodrug could be monitored in real-time by infrared thermal imaging, fluorescence imaging and computed tomography (CT). More importantly, the combination effects of photothermal therapy (PTT), photodynamic therapy (PDT) and chemotherapy was demonstrated to dramatically suppress solid tumors without recurrence in vivo. Featured by the low systemic toxicity and high biocompatibility, this nanoplatform could be a promising derivative of Bi2S3 NSs for imaging-guided theranostics of cancer.
PMID: 30654184 [PubMed - as supplied by publisher]
Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion.
Biomaterials. 2019 Jan 09;197:146-160
Authors: Mathew B, Ravindran S, Liu X, Torres L, Chennakesavalu M, Huang CC, Feng L, Zelka R, Lopez J, Sharma M, Roth S
Retinal ischemia is a major cause of vision loss and impairment and a common underlying mechanism associated with diseases such as glaucoma, diabetic retinopathy, and central retinal artery occlusion. The regenerative capacity of the diseased human retina is limited. Our previous studies have shown the neuroprotective effects of intravitreal injection of mesenchymal stem cells (MSC) and MSC-conditioned medium in retinal ischemia in rats. Based upon the hypothesis that the neuroprotective effects of MSCs and conditioned medium are largely mediated by extracellular vesicles (EVs), MSC derived EVs were tested in an in-vitro oxygen-glucose deprivation (OGD) model of retinal ischemia. Treatment of R28 retinal cells with MSC-derived EVs significantly reduced cell death and attenuated loss of cell proliferation. Mechanistic studies on the mode of EV endocytosis by retinal cells were performed in vitro. EV endocytosis was dose- and temperature-dependent, saturable, and occurred via cell surface heparin sulfate proteoglycans mediated by the caveolar endocytic pathway. The administration of MSC-EVs into the vitreous humor 24 h after retinal ischemia in a rat model significantly enhanced functional recovery, and decreased neuro-inflammation and apoptosis. EVs were taken up by retinal neurons, retinal ganglion cells, and microglia. They were present in the vitreous humor for four weeks after intravitreal administration, with saturable binding to vitreous humor components. Overall, this study highlights the potential of MSC-EV as biomaterials for neuroprotective and regenerative therapy in retinal disorders.
PMID: 30654160 [PubMed - as supplied by publisher]
Glucocorticoid-mediated effects on angiogenesis in solid tumors.
J Steroid Biochem Mol Biol. 2019 Jan 14;:
Authors: Martens B, Drebert Z
Angiogenesis is essential in tumor development to maintain the oxygen and nutrient supply. Glucocorticoids have shown both direct and indirect angiostatic properties in various types of solid cancers. In most of the reported cases glucocorticoid-mediated actions involved suppression of multiple pro-angiogenic factors expression by cancer cells. The anti-angiogenic properties of glucocorticoids correlated with diminished tumor vasculature and reduced tumor growth in multiple in vivo studies. However, when glucocorticoid treatment is considered, possible adverse events should be taken into account. Additional research is needed to further test the use of these steroidal drugs in cancer therapy.
PMID: 30654109 [PubMed - as supplied by publisher]
Carbon monoxide poisoning in Denmark with focus on mortality and factors contributing to mortality.
PLoS One. 2019;14(1):e0210767
Authors: Simonsen C, Thorsteinsson K, Mortensen RN, Torp-Pedersen C, Kjærgaard B, Andreasen JJ
INTRODUCTION: Carbon monoxide (CO) poisoning is frequent worldwide but knowledge regarding the epidemiology is insufficient. The aim of this study was to clarify the extent of this intoxication, its mortality and factors associated with mortality.
MATERIALS AND METHODS: National databases from Statistics Denmark were used to identify individuals who suffered from CO-poisoning during 1995-2015, as well as information regarding co-morbidities, mortality and manner of death.
RESULTS: During the period from 1995 to 2015, 22,930 patients suffered from CO-poisoning in Denmark, and 21,138 of these patients (92%) were hospitalized. A total of 2,102 patients died within the first 30 days after poisoning (9.2%). Among these, 1,792 (85% of 2,102) were declared dead at the scene and 310 (15% of 2,102) died during hospitalization. Deaths due to CO-poisoning from smoke were intentional in 6.3% of cases, whereas deaths due to CO containing gases were intentional in 98.0% of cases. Among patients who survived >30 days, there was no significant difference in survival when comparing hyperbaric oxygen therapy (HBO) treatment with no HBO treatment after adjustment for age and co-morbidities such as drug abuse, psychiatric disease, stroke, alcohol abuse, arterial embolism, chronic obstructive pulmonary disease, cerebrovascular disease and atrial fibrillation. Several co-morbidities predicted poorer outcomes for patients who survived the initial 30 days.
CONCLUSIONS: Poisoning from smoke and/or CO is a frequent incident in Denmark accounting for numerous contacts with hospitals and deaths. Both intoxication and mortality are highly associated with co-morbidities interfering with cognitive and physical function. Treatment with HBO was not seen to have an effect on survival.
PMID: 30653615 [PubMed - in process]
Superoxide Radical Photogenerator with Amplification Effect: Surmounting the Achilles' heels of Photodynamic Oncotherapy.
J Am Chem Soc. 2019 Jan 17;:
Authors: Li M, Xiong T, Du J, Tian R, Xiao M, Guo L, Long S, Fan J, Sun W, Shao K, Song X, Foley JW, Peng X
Strong oxygen dependence, poor tumor targeting, and limited treatment depth have been considered as the "Achilles' heels" facing the clinical usage of photodynamic therapy (PDT). Different from common approaches, here, we propose an innovative tactic by using photon-initiated dyad cationic superoxide radical (O2-•) generator (ENBOS) featuring "0 + 1 > 1" amplification effect to simultaneously overcome these drawbacks. In particular, by taking advantage of the Förster resonance energy transfer theory, the energy donor successfully endows ENBOS with significantly enhanced NIR absorbance and photon utility, which in turn lead to ENBOS more easily activated and generating more O2-• in deep tissues, thus dramatically intensifies the type I PDT against hypoxic deep tumors. Moreover, benefiting from the dyad cationic feature, ENBOS achieves superior "structure-inherent targeting" abilities with the signal-to-background ratio as high as 25.2 at 48 h post intravenous injection, offering opportunities for accurate imaging-guided tumor treatment. Meanwhile, the intratumoral accumulation and retention performance are also markedly improved (> 120 h). Based on these unique merits, ENBOS selectively inhibits the deep-seated hypoxic tumor proliferation at a low light-dose irradiation. Therefore, this delicate design may open up new horizons and cause a paradigm change for PDT in future cancer therapy.
PMID: 30652866 [PubMed - as supplied by publisher]
Gamma-Secretase Inhibitor, DAPT, Prevents the Development of Retinopathy of Prematurity in a Rat Model by Regulating the Delta-Like Ligand 4/Notch Homolog-1 (DLL4/Notch-1) Pathway.
Med Sci Monit. 2019 Jan 17;25:492-499
Authors: Sun W, Li J, Li Y, Zheng J, Zhang X, Huang X, Li S
BACKGROUND Retinopathy of prematurity (ROP), or retrolental fibroplasia, affects premature infants who have undergone intensive care with oxygen therapy. This study aimed to investigate the inhibitory effect of the gamma-secretase inhibitor, DAPT, on neovascularization and its mechanism in a rat model of ROP. MATERIAL AND METHODS Sixty neonatal Sprague-Dawley (SD) rats included the control group (n=20), the model group (n=20), and the DAPT-treated group (n=20). The rat model of ROP was established using repeat cycles of oxygen inhalation. Enzyme-linked immunosorbent assay (ELISA) measured serum levels of vascular endothelial growth factor (VEGF), VEGF receptor-1 (VEGFR-1), and VEGFR-2. Histology of the retinal tissue included immunohistochemistry for the expression of Notch homolog-1 (Notch-1) and delta-like ligand 4 (DLL4). Retinal mRNA levels of DLL4, Notch-1, VEGF, VEGFR-1, and VEGFR-2 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS The rat model of ROP showed increased serum levels of VEGF, VEGFR-1, and VEGFR-2 compared with the control group, which were decreased in the DAPT group. Histology of the retinal tissue in the model group showed degeneration of the retinal ganglion cells, and immunohistochemistry showed increased expression of Notch-1 and DLL4 compared with the control group and DAPT group. Retinal tissue in the model group had increased mRNA levels of DLL4, Notch-1, VEGF, VEGFR-1, and VEGFR-2 compared with the control group, and the DAPT group. CONCLUSIONS In a rat model, treatment with DAPT reduced the retinal changes associated with ROP with a mechanism that involved VEGF and its receptors through the DLL4/Notch-1 pathway.
PMID: 30652694 [PubMed - in process]
A Comprehensive Review of Oxidative Stress as the Underlying Mechanism in Atherosclerosis and the Inefficiency of Antioxidants to Revert this Process.
Curr Pharm Des. 2019 Jan 15;:
Authors: Cabezas KG, Gómez-Fernandez CR, Vazquez-Padron R
BACKGROUND: Cardiovascular diseases account for the highest mortality rate in the United States. The major underlying mechanism driving the onset and maintenance of cardiovascular diseases is atherosclerosis. Atherosclerosis is a chronic disease affecting large and medium size arteries; it proceeds through four main stages along the different decades of life, beginning at birth. Atherosclerosis is a consequence of Oxidative stress, where homeostasis between endogenous antioxidants and reactive oxygen species is disrupted. Failure of intrinsic antioxidants and prophylactic antioxidant supplements to prevent atherosclerosis formation is an ongoing area of research on the race to avert, manage and cure atherosclerosis.
METHODS: The purpose of this work is to elucidate the actions of reactive oxygen species and oxidative stress on the formation of atherosclerosis as well as the different stages of atherosclerosis and the different mechanisms to prevent it. Through extensive review of scientific literature, this paper correlates cell damage caused by oxidative stress to atheromatous plaque formation, as well as an in-depth analysis of high-density lipoproteins and enzymatic and non-enzymatic antioxidant role on atherosclerosis prevention. Antioxidant mechanism are overwhelmed by atherosclerotic processes and fail to be the ideal treatment of atherosclerosis. There is no scientific data that correlates prophylactic and non-prophylactic antioxidant treatment to a decrease in mortality or comorbidities pertaining to atherosclerosis. This is thought to be due to lack of consensus of optimal therapeutic doses, lack reliable markers indicating which patient is to benefit from therapy and the chemical complexity of antioxidants in vivo. Current treatments for atherosclerosis include HMG-CoA reductase inhibitors which target directly low-density lipoproteins to tackle atherosclerotic plaque formation.
CONCLUSION: HMG-CoA reductase inhibitors are not enough for the treatment of atherosclerosis given the complexity of the disease which has immune, musculoskeletal, genetic and hematologic aspects besides the involvement of lipids and lipoproteins. Therefore, other pharmacologic targets such as the PCSK9 enzyme and NFK- β should be researched in depth as possible treatments for atherosclerosis.
PMID: 30652635 [PubMed - as supplied by publisher]
Impact of hyperoxia on cardiac pathophysiology.
J Cell Physiol. 2019 Jan 16;:
Authors: Rodgers JL, Iyer D, Rodgers LE, Vanthenapalli S, Panguluri SK
Mechanical ventilation with high oxygen therapy (hyperoxia) is widely implemented in critical care and ICU settings. Although supplemental oxygen is beneficial to treat hypoxia, its use is also associated with poor outcomes and high mortality in patients. Lung injury due to hyperoxia exposure has been well-documented in patients, including in adults and neonates. Thus, lung injury due to hyperoxia has been extensively researched in both preclinical and clinical studies. However, hyperoxia has also been shown to be associated with hemodynamic changes in patients in ICU, including reductions in heart rate, stroke volume, and cardiac output. In addition, certain experimental studies report that hyperoxia exposure in neonates results in cardiac dysfunction in later adult life. Despite this, until recently, the impact of hyperoxia within the heart has not been well studied, or reported, specifically in adult experimental models. To close this significant gap, our lab has sought to clarify hyperoxia-induced cardiac pathophysiology in adult murine models. This review discusses the current findings regarding the cardiovascular impact of hyperoxia exposure.
PMID: 30652312 [PubMed - as supplied by publisher]
Low-Concentration Oxygen/Ozone Treatment Attenuated Radiculitis and Mechanical Allodynia via PDE2A-cAMP/cGMP-NF-κB/p65 Signaling in Chronic Radiculitis Rats.
Pain Res Manag. 2018;2018:5192814
Authors: Wang J, Wu M, Lin X, Li Y, Fu Z
Background: Oxygen/ozone therapy is a minimally invasive technique for the treatment of radiculitis from lumbar disc herniation. This study aimed at investigating whether intrathecal administration of low-concentration oxygen/ozone could attenuate chronic radiculitis and mechanical allodynia after noncompressive lumbar disc herniation and at elucidating the underlying mechanisms.
Methods: First, we transplanted autologous nucleus pulposus into dorsal root ganglions to establish chronic radiculitis in rats. Then, filtered oxygen or oxygen/ozone (10, 20, or 30 μg/mL) was intrathecally injected on day 1 after surgery. The ipsilateral paw withdrawal thresholds (PWTs) to mechanical stimuli were tested daily with von Frey filaments. The expression of the tumor necrosis factor- (TNF-) α, interleukin- (IL-) 1β, IL-6, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), phosphodiesterase 2A (PDE2A), and nuclear factor- (NF-) κB/p65 in spinal dorsal horns was measured by enzyme-linked immunosorbent assay, polymerase chain reaction, and western blot on day 7 after surgery.
Results: Chronic radiculitis was established in rats. Intrathecal administration of 10 μg/mL, 20 μg/mL, or 30 μg/mL oxygen/ozone significantly attenuated the decreased mechanical PWTs, downregulated the overexpression of spinal TNF-α, IL-1β, and IL-6, and increased the expression of cGMP and cAMP in chronic radiculitis rats. In addition, the effects of treatment with 20 μg/mL oxygen/ozone were greater than the effects of the 10 μg/mL or 30 μg/mL doses. Moreover, intrathecal administration of 20 μg/mL oxygen/ozone reversed the increased levels of spinal PDE2A and NF-κB/p65 mRNA and protein expressions in rats with chronic radiculitis.
Conclusion: Intrathecal administration of low-concentration oxygen/ozone alleviated mechanical allodynia and attenuated radiculitis, likely by a PDE2A-cGMP/cAMP-NF-κB/p65 signaling pathway in chronic radiculitis rats.
PMID: 30651902 [PubMed - in process]
The Siconolfi step test: a valid and reliable assessment of cardiopulmonary fitness in older men with prostate cancer.
Eur Rev Aging Phys Act. 2019;16:1
Authors: Lemanska A, Poole K, Aning JJ, Griffin BA, Manders R, Saxton JM, Wainwright J, Faithfull S
Background: Assessing fitness and promoting regular physical activity can improve health outcomes and early recovery in prostate cancer. This is however, underutilised in clinical practice. The cardiopulmonary exercise test (CPET) is increasingly being used pre-treatment to measure aerobic capacity and peak oxygen consumption (VO2peak - a gold standard in cardiopulmonary fitness assessment). However, CPET requires expensive equipment and may not always be appropriate. The Siconolfi step test (SST) is simpler and cheaper, and could provide an alternative.The aim of this study was to evaluate the validity and reliability of SST for predicting cardiopulmonary fitness in men with prostate cancer. Men were recruited to this two-centre study (Surrey and Newcastle, United Kingdom) after treatment for locally advanced prostate cancer. They had one or more of three risk factors: elevated blood pressure, overweight (BMI > 25), or androgen deprivation therapy (ADT). Cardiopulmonary fitness was measured using SST and cycle ergometry CPET, at two visits three months apart. The validity of SST was assessed by comparing it to CPET. The VO2peak predicted from SST was compared to the VO2peak directly measured with CPET. The reliability of SST was assessed by comparing repeated measures. Bland-Altman analysis was used to derive limits of agreement in validity and reliability analysis.
Results: Sixty-six men provided data for both SST and CPET. These data were used for validity analysis. 56 men provided SST data on both visits. These data were used for reliability analysis. SST provided valid prediction of the cardiopulmonary fitness in men > 60 years old. The average difference between CPET and SST was 0.64 ml/kg/min with non-significant positive bias towards CPET (P = 0.217). Bland-Altman 95% limits of agreement of SST with CPET were ± 7.62 ml/kg/min. SST was reliable across the whole age range. Predicted VO2peak was on average 0.53 ml/kg/min higher at Visit 2 than at Visit 1 (P = 0.181). Bland-Altman 95% limits of agreement between repeated SST measures were ± 5.84 ml/kg/min.
Conclusions: SST provides a valid and reliable alternative to CPET for the assessment of cardiopulmonary fitness in older men with prostate cancer. Caution is advised when assessing men 60 years old or younger because the VO2peak predicted with SST was significantly lower than that measured with CPET.
PMID: 30651889 [PubMed]
Therapeutic effect of combined hyperbaric oxygen and radiation therapy for single brain metastasis and its influence on osteopontin and MMP-9.
Exp Ther Med. 2019 Jan;17(1):465-471
Authors: Tao J, Gao Z, Huang R, Li H
The present study aimed to investigate the therapeutic effect of combined hyperbaric oxygen and radiation therapy for the treatment of single brain metastasis (SBM), as well as its influence on osteopontin (OPN) and matrix metalloproteinase-9 (MMP-9). A total of 86 patients with SBM were admitted to Hongqi Hospital from January 2013 to January 2016 and those included within the study were randomly divided into two groups. The control group was only treated with whole brain radiotherapy, while the observation group was treated with hyperbaric oxygenation combined with whole brain radiotherapy. OPN and MMP-9 expression was measured in each group by ELISA and the results prior to and following treatment were compared. The total effective rate (patients with complete remission, partial remission or stabilized lesions) in the observation group (95.3%) was significantly increased compared with the control group (67.4%). However, the OPN and MMP-9 protein levels observed in the observation group were significantly reduced compared with the control group (P<0.05). In addition, the quality of life and the incidence of adverse reactions in the observation group were significantly improved compared with the control group (P<0.05). For patients with SBM, hyperbaric oxygenation combined with radiotherapy may improve the efficiency of treatment and should be considered for further investigation and use within a clinical setting.
PMID: 30651823 [PubMed]
Evaluation of glutathione peroxidase in the blood and tumor tissue of oral squamous cell carcinoma patients.
J Oral Maxillofac Pathol. 2018 Sep-Dec;22(3):447
Authors: Deshpande KC, Kulkarni MM, Rajput DV
Aims and Objectives: The lowered antioxidant capacity and the oxidant-antioxidant imbalance have been considered to play a role in multistage carcinogenesis. The deleterious effects produced by reactive oxygen species depend on the imbalance between oxidant and antioxidant status in the body, so this study is aimed to evaluate the levels of antioxidant enzyme, glutathione peroxidase (GPx), in the blood and tumor tissues of oral squamous cell carcinoma (OSCC) patients in comparison with healthy controls.
Materials and Methods: The study comprised of 38 participants divided into two groups. Group 1 comprised of 20 patients with OSCC and Group 2 comprised of age- and sex-matched 18 healthy individuals free of any habits and systemic illness. The levels of GPx were estimated in the blood and tissue samples in both groups by Paglia and Valentine method using a Commercial Biochemical assay kit (RANDOX), by ultraviolet-visible spectrophotometer.
Results: The GPx levels were elevated in the whole blood and the tissue samples of OSCC cases as compared to the control group. It was also found that the GPx levels were increased in the tumor tissue with respect to the histopathological grading of the OSCC cases.
Conclusion: Detection of antioxidant status may be useful to choose correct radiotherapy or chemotherapy, to monitor the effectiveness of the therapeutic strategy and to determine tumor resistance to therapy. Hence, the evaluation of GPx enzyme level can be used as a prognostic marker in patients with OSCC.
PMID: 30651704 [PubMed]
Cascade enzymes within self-assembled hybrid nanogel mimicked neutrophil lysosomes for singlet oxygen elevated cancer therapy.
Nat Commun. 2019 Jan 16;10(1):240
Authors: Wu Q, He Z, Wang X, Zhang Q, Wei Q, Ma S, Ma C, Li J, Wang Q
As the first line of innate immune cells to migrate towards tumour tissue, neutrophils, can immediately kill abnormal cells and activate long-term specific adaptive immune responses. Therefore, the enzymes mediated elevation of reactive oxygen species (ROS) bioinspired by neutrophils can be a promising strategy in cancer immunotherapy. Here, we design a core-shell supramolecular hybrid nanogel via the surface phosphatase triggered self-assembly of oligopeptides around iron oxide nanoparticles to simulate productive neutrophil lysosomes. The cascade reaction of superoxide dismutase (SOD) and chloroperoxidase (CPO) within the bioinspired nanogel can convert ROS in tumour tissue to hypochlorous acid (HOCl) and the subsequent singlet oxygen (1O2) species. Studies on both cells and animals demonstrate successful 1O2-mediated cell/tumour proliferation inhibition, making this enzyme therapy capable for treating tumours without external energy activation.
PMID: 30651559 [PubMed - in process]
Is an IOTA of evidence enough?
CJEM. 2019 Jan 17;:1-3
Authors: Davis SNP, Di Nicola N, Gosselin S
Clinical questionDo patients with acute illness admitted to the hospital and treated with liberal oxygen therapy compared with those treated with conservative oxygen therapy have differences in mortality and morbidity?Article chosenChu DK, Kim LH, Young PJ, et al. Mortality and morbidity in acutely ill adults treated with liberal versus conservative oxygen therapy (IOTA): a systematic review and meta-analysis. Lancet 2018;391(10131):1693-705. OBJECTIVES: To analyse the existing literature to assess the potential benefits or harms of supplemental oxygen use in acutely ill patients.
PMID: 30651153 [PubMed - as supplied by publisher]
On the Mechanism of Hyperthermia-Induced BRCA2 Protein Degradation.
Cancers (Basel). 2019 Jan 15;11(1):
Authors: van den Tempel N, Zelensky AN, Odijk H, Laffeber C, Schmidt CK, Brandsma I, Demmers J, Krawczyk PM, Kanaar R
The DNA damage response (DDR) is a designation for a number of pathways that protects our DNA from various damaging agents. In normal cells, the DDR is extremely important for maintaining genome integrity, but in cancer cells these mechanisms counteract therapy-induced DNA damage. Inhibition of the DDR could therefore be used to increase the efficacy of anti-cancer treatments. Hyperthermia is an example of such a treatment-it inhibits a sub-pathway of the DDR, called homologous recombination (HR). It does so by inducing proteasomal degradation of BRCA2 -one of the key HR factors. Understanding the precise mechanism that mediates this degradation is important for our understanding of how hyperthermia affects therapy and how homologous recombination and BRCA2 itself function. In addition, mechanistic insight into the process of hyperthermia-induced BRCA2 degradation can yield new therapeutic strategies to enhance the effects of local hyperthermia or to inhibit HR. Here, we investigate the mechanisms driving hyperthermia-induced BRCA2 degradation. We find that BRCA2 degradation is evolutionarily conserved, that BRCA2 stability is dependent on HSP90, that ubiquitin might not be involved in directly targeting BRCA2 for protein degradation via the proteasome, and that BRCA2 degradation might be modulated by oxidative stress and radical scavengers.
PMID: 30650591 [PubMed]
Can Early Introduction of Palliative Care Limit Intensive Care, Emergency and Hospital Admissions in Patients with Severe Chronic Obstructive Pulmonary Disease? A Pilot Randomized Study.
Respiration. 2019 Jan 16;:1-10
Authors: Janssens JP, Weber C, Herrmann FR, Cantero C, Pessina A, Matis C, Merlet Viollet R, Boiche-Brouillard L, Stirnemann J, Pautex S
BACKGROUND: Despite their poor prognosis, patients with severe chronic obstructive pulmonary disease (COPD) have little access to palliative care and tend to have a high rate of hospital and intensive care unit (ICU) admissions during their last year of life.
OBJECTIVES: To determine the feasibility of a home palliative care intervention during 1 year versus usual care, and the possible impact of this intervention on emergency, hospital and ICU admissions, survival, mood, and health-related quality of life (HRQL).
METHODS: Prospective controlled study of patients with severe COPD (GOLD stage III or IV) and long-term oxygen therapy and/or home noninvasive ventilation and/or one or more hospital admissions in the previous year for acute exacerbation, randomized to usual care versus usual care with add-on monthly intervention by palliative care specialists at home for 12 months.
RESULTS: Of 315 patients screened, 49 (15.5%) were randomized (26 to early palliative care; 23 to the control group); aged (mean ± SD) 71 ± 8 years; FEV1 was 37 ± 14% predicted; 88% with a COPD assessment test score > 10; 69% on long-term oxygen therapy or home noninvasive ventilation. The patients accepted the intervention and completed the assessment scales. After 1 year, there was no difference between groups in symptoms, HRQL and mood, and there was a nonsignificant trend for higher admission rates to hospital and emergency wards in the intervention group.
CONCLUSION: Although this pilot study was underpowered to formally exclude a benefit from palliative care in severe COPD, it raises several questions as to patient selection, reluctance to palliative care in this group, and modalities of future trials.
PMID: 30650418 [PubMed - as supplied by publisher]
Alveolar Macrophage Apoptosis-Associated Bacterial Killing Helps Prevent Murine Pneumonia.
Am J Respir Crit Care Med. 2019 Jan 16;:
Authors: Preston JA, Bewley MA, Marriott HM, Houghton AM, Mohasin M, Jubrail J, Morris L, Stephenson YL, Cross S, Greaves DR, Craig RW, van Rooijen N, Bingle CD, Read RC, Mitchell TJ, Whyte MKB, Shapiro SD, Dockrell DH
RATIONALE: Antimicrobial resistance challenges therapy of pneumonia. Enhancing macrophage microbicidal responses would combat this problem but is limited by our understanding of how alveolar macrophages (AM) kill bacteria.
OBJECTIVES: To define the role and mechanism of AM apoptosis-associated bacterial killing in the lung.
METHODS: We generated a unique CD68.hMcl-1 transgenic mouse with macrophage-specific over-expression of the human anti-apoptotic Mcl-1 protein, a factor upregulated in AM from patients at increased risk of community-acquired pneumonia, to address the requirement for apoptosis-associated killing.
MEASUREMENTS AND MAIN RESULTS: Wild-type and transgenic macrophages demonstrated comparable ingestion and initial phagolysosomal killing of bacteria. Continued ingestion (for > 12 h) overwhelmed initial killing and a second late-phase microbicidal response killed viable bacteria in wild-type macrophages, but this response was blunted in CD68.hMcl-1 transgenic macrophages. The late-phase of bacterial killing required both caspase-induced generation of mitochondrial reactive oxygen species (mROS) and nitric oxide (NO), whose peak generation coincided with the late-phase of killing. The CD68.hMcl-1 transgene prevented mROS but not NO generation. Apoptosis-associated killing enhanced pulmonary clearance of Streptococcus pneumoniae and Haemophilus influenzae in wild-type but not CD68.hMcl-1 transgenic mice. Bacterial clearance was enhanced in vivo in CD68.hMcl-1 transgenic mice by reconstitution of apoptosis with BH3 mimetics or clodronate-encapsulated liposomes. Apoptosis-associated killing was not activated during Staphylococcus aureus lung infection.
CONCLUSIONS: Mcl-1 upregulation prevents macrophage apoptosis-associated killing and establishes that apoptosis-associated killing is required to allow AM to clear ingested bacteria. Engagement of macrophage apoptosis should be investigated as a novel host-based antimicrobial strategy.
PMID: 30649895 [PubMed - as supplied by publisher]
Nanohydroxyapatite exerts cytotoxic effects and prevents cellular proliferation and migration in glioma cells.
Toxicol Sci. 2019 Jan 15;:
Authors: Gorojod RM, Porte Alcon S, Dittler ML, Gonzalez MC, Kotler ML
Hydroxyapatite (Ca10(PO4)6(OH)2; HAP) is an essential component of the human bone inorganic phase. At the nanoscale level, nanoHAP (nHAP) presents marked emergent properties differing substantially from those of the bulk counterpart. Interestingly, these properties depend on nanoparticle characteristics. In this study, we investigated the cytotoxicity of rod-shaped crystalline nHAP (10- 20 nm x 50- 100 nm) in both normal (ARPE-19, BV-2) and tumoral (HepG2, HEp-2, A549 and C6) cells. We found that nHAP was cytotoxic in tumor HEp-2, A549 and C6 cells. Moreover, it induced an expansion of the lysosomal compartment at sub-lethal concentrations in different cell lines, while lysosomal membrane damage was not detected. In C6 glioma cells, the most sensitive cell line to nHAP, these nanoparticles increased reactive oxygen species (ROS) production and induced DNA damage measured by γ-H2AX phosphorylation. Interestingly, our data also shows for the first time that nHAP affects both cell unlimited proliferative capacity and cell migration, two of the major pathways involved in cancer progression. The present results showed the cytotoxic and antiproliferative effects of nHAP and suggest its potential as an alternative agent for glioma therapy.
PMID: 30649537 [PubMed - as supplied by publisher]
Cardiac output monitoring: Technology and choice.
Ann Card Anaesth. 2019 Jan-Mar;22(1):6-17
Authors: Kobe J, Mishra N, Arya VK, Al-Moustadi W, Nates W, Kumar B
The accurate quantification of cardiac output (CO) is given vital importance in modern medical practice, especially in high-risk surgical and critically ill patients. CO monitoring together with perioperative protocols to guide intravenous fluid therapy and inotropic support with the aim of improving CO and oxygen delivery has shown to improve perioperative outcomes in high-risk surgical patients. Understanding of the underlying principles of CO measuring devices helps in knowing the limitations of their use and allows more effective and safer utilization. At present, no single CO monitoring device can meet all the clinical requirements considering the limitations of diverse CO monitoring techniques. The evidence for the minimally invasive CO monitoring is conflicting; however, different CO monitoring devices may be used during the clinical course of patients as an integrated approach based on their invasiveness and the need for additional hemodynamic data. These devices add numerical trend information for anesthesiologists and intensivists to use in determining the most appropriate management of their patients and at present, do not completely prohibit but do increasingly limit the use of the pulmonary artery catheter.
PMID: 30648673 [PubMed - in process]
Cucurbituril enhance the photosensitization of porphyrins in Neuroblastoma cells.
Photodiagnosis Photodyn Ther. 2019 Jan 12;:
Authors: Li X, Bo X, Guo Y, Xiao Y, Xiao S
Neuroblastoma is the most common extracranial solid tumor of childhood. Advancements in treatments have improved survival rate of child suffering from this ailment. Novel therapeutic techniques may further reduce cancer related mortality. One of the several emerging therapeutic options is Photodynamic Therapy (PDT) that uses light activated photosensitizer (PS) inducing cell death by apoptosis and/or necrosis. Nanotechnology has contributed to improving photosensitizer for PDT, and increasing the efficiency of therapy using porphyrins and their derivatives. Efforts have been done to develop better mechanism to improve PS and consequently PDT effect. In this study, we investigated the efficacy of the PDT using porphyrins (TPOR) and TPOR/(CB)4 (TPOR: CB = 1: 4). Here we report the PDT effect of TPOR and TPOR/(CB)4 in the treatment of the human neuroblastoma cell line (SH-SY5Y). The TPOR and TPOR/(CB)4 not show more significant dark-cytotoxicity and TPOR/(CB)4 had a more strong photodynamic effects than TPOR through generating reactive oxygen species (ROS) under irradiation with a 525 nm laser. The high photodynamic efficiency of TPOR/(CB)4 suggests that it has the potential to be a PDT agent.
PMID: 30648639 [PubMed - as supplied by publisher]
Oxidative stress and kidney function: a brief update.
Curr Pharm Des. 2019 Jan 12;:
Authors: Coppolino G, Leonardi G, Andreucci M, Bolignano D
BACKGROUND: ROS are highly reactive and cause in single cells: protein alteration, DNA damage, cellular senescence and apoptosis; while the effect of ROS in biological tissues leads to a harmful oxidation effect on all their biochemical components: lipids, proteins, carbohydrates, and nucleic acids. Oxidative stress plays a role in the pathophysiology of renal impairment and is a mediator of CKD progression; furthermore during substitutive therapy with haemodialysis or peritoneal dialysis and in case of transplantation, organism continues to be exposed to oxidation causing the development of major systemic comorbidities in particular cardiovascular diseases.
METHODS: In this review we summarized some information regarding the link between kidney and oxidative stress. The kidneys maintain plasma homeostasis by filtering plasma and reabsorbing approximately 99% of the filtrate back into the plasma. This enormous reabsorption work requires a great consume of molecular oxygen (O2) due to active transport.
CONCLUSION: Accruing evidences indicated the kidney as a fundamental organ in reactive oxygen species (ROS) production.
PMID: 30648504 [PubMed - as supplied by publisher]
An Update on Topical Photodynamic Therapy for Clinical Dermatologists.
J Dermatolog Treat. 2019 Jan 16;:1-37
Authors: Nguyen K, Khachemoune A
INTRODUCTION: Photodynamic therapy (PDT) involves the application of a topical photosensitizer, irradiation with light, and oxygen to produce cytotoxic reactive oxygen species that selectively destroy damaged cells while leaving normal skin intact. Topical PDT is a commonly used treatment for non-melanoma skin cancers (NMSCs) due to its excellent clearance rate and cosmetic outcomes. However, PDT is emerging as an off-label treatment modality for many dermatological conditions.
METHODS: A literature review using MEDLINE was performed to identify randomized controlled trials conducted for currently approved and off-label clinical indications and photosensitizers for PDT between 2012 and 2018.
RESULTS: The photosensitizer indole-3 acetic acid reduces the incubation time (<30 minutes), avoids the need for photoprotection after irradiation, and inflicts minimal pain. Cyclic PDT in individuals with evidence of field cancerization delays the mean time of actinic keratosis appearance and reduces the total number of new actinic keratoses. Substantial evidence exists outlining the utility of PDT in photorejuvenation due to its ability to improve skin texture, wrinkles, and firmness. The addition of microdermabrasion, microneedling, curettage, or various lasers improves clinical efficacy and cosmetic outcomes.
DISCUSSION: PDT applications are expanding rapidly. Clinicians must stay up to date regarding the efficacy and safety of PDT applications.
PMID: 30648439 [PubMed - as supplied by publisher]
Molybdenum sulfide-reduced graphene oxide p-n heterojunction nanosheets with anchored oxygen generating manganese dioxide nanoparticles for enhanced photodynamic therapy.
Chem Sci. 2018 Dec 28;9(48):8982-8989
Authors: Kapri S, Bhattacharyya S
In an unprecedented approach, p-n heterojunction nanosheets comprising ∼5 nm thick p-type MoS2 nanoplates integrated onto n-type nitrogen doped reduced graphene oxide (n-rGO) have been employed for photodynamic therapy (PDT). When near infrared (NIR) light with 980 nm wavelength was irradiated on this nanocomposite, effective electron-hole separation was obtained across the heterojunction. The nanosheets were modified with lipoic acid functionalized poly(ethylene glycol) to provide better biocompatibility and colloidal stability in physiological solution. The surface decorated 3-5 nm MnO2 nanoparticles (NPs) triggered the disproportionation of intracellular H2O2 which improved generation of reactive oxygen species (ROS) for enhanced PDT cancer therapy, studied in vitro. The role of N-doping in rGO and the effect of immobilization of MnO2 NPs were systematically investigated by control experiments. Our smartly designed p-MoS2/n-rGO-MnO2-PEG nanosheets outperform conventional PDT agents by overcoming limitations such as low absorption band, unfavourable bioavailability and limitations in tissue oxygenation.
PMID: 30647890 [PubMed]
Efficacy of Glucocorticoids and Calcineurin Inhibitors for Anti-aminoacyl-tRNA Synthetase Antibody-positive Polymyositis/dermatomyositis-associated Interstitial Lung Disease: A Propensity Score-matched Analysis.
J Rheumatol. 2019 Jan 15;:
Authors: Hozumi H, Fujisawa T, Nakashima R, Yasui H, Suzuki Y, Kono M, Karayama M, Furuhashi K, Enomoto N, Inui N, Nakamura Y, Mimori T, Suda T
OBJECTIVE: The optimal treatment strategy for anti-aminoacyl-tRNA synthetase antibody-positive polymyositis/dermatomyositis-associated interstitial lung disease (anti-ARS-PM/DM-ILD) is yet to be established. We aimed to evaluate the efficacy of glucocorticoids and calcineurin inhibitors (CNI) in patients with ARS-PM/DM-ILD.
METHODS: Progression-free survival (PFS) and overall survival rates were retrospectively evaluated in 32 consecutive patients with ARS-PM/DM-ILD. Disease progression was defined as deterioration in PM/DM-ILD (including recurrence). Predictive factors associated with PFS were analyzed by Cox hazards analysis. The efficacy of first-line prednisolone (PSL) plus CNI therapy was compared with that of PSL monotherapy using propensity score-matched analysis.
RESULTS: Overall, 20 (62.5%) and 12 (37.5%) patients received first-line therapy with PSL + CNI and PSL, respectively. The 2-year PFS and 5-year survival rates in the overall cohort were 68.8% and 96.9%, respectively. On multivariate analysis, arterial oxygen pressure (HR 0.86) and PSL monotherapy (vs PSL + CNI; HR 7.29) showed an independent association with PFS. Baseline characteristics of propensity score-matched PSL + CNI and PSL groups were similar. The 2-year PFS rate was significantly higher in the matched PSL + CNI group than in the matched PSL group. All patients who experienced disease progression during first-line therapy were subsequently treated with second-line therapies. The 5-year survival rates of both the matched PSL + CNI and PSL groups were favorable.
CONCLUSION: Propensity score-matched analysis demonstrated that first-line PSL + CNI therapy for patients with ARS-PM/DM-ILD significantly improved the PFS compared with PSL monotherapy, although there was no significant difference regarding longterm survival.
PMID: 30647164 [PubMed - as supplied by publisher]
Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial: study protocol for a multicentre international trial of cardiac output-guided fluid therapy with low-dose inotrope infusion compared with usual care in patients undergoing major elective gastrointestinal surgery.
BMJ Open. 2019 Jan 15;9(1):e023455
Authors: Edwards MR, Forbes G, MacDonald N, Berdunov V, Mihaylova B, Dias P, Thomson A, Grocott MP, Mythen MG, Gillies MA, Sander M, Phan TD, Evered L, Wijeysundera DN, McCluskey SA, Aldecoa C, Ripollés-Melchor J, Hofer CK, Abukhudair H, Szczeklik W, Grigoras I, Hajjar LA, Kahan BC, Pearse RM, OPTIMISE II investigators
INTRODUCTION: Postoperative morbidity and mortality in older patients with comorbidities undergoing gastrointestinal surgery are a major burden on healthcare systems. Infections after surgery are common in such patients, prolonging hospitalisation and reducing postoperative short-term and long-term survival. Optimal management of perioperative intravenous fluids and inotropic drugs may reduce infection rates and improve outcomes from surgery. Previous small trials of cardiac-output-guided haemodynamic therapy algorithms suggested a modest reduction in postoperative morbidity. A large definitive trial is needed to confirm or refute this and inform widespread clinical practice.
METHODS: The Optimisation of Perioperative Cardiovascular Management to Improve Surgical Outcome II (OPTIMISE II) trial is a multicentre, international, parallel group, open, randomised controlled trial. 2502 high-risk patients undergoing major elective gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intravenous fluid combined with low-dose inotrope infusion, or usual care. The trial intervention will be carried out during and for 4 hours after surgery. The primary outcome is postoperative infection of Clavien-Dindo grade II or higher within 30 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation; however, outcome assessors will be blinded when feasible. Participant recruitment started in January 2017 and is scheduled to last 3 years, within 50 hospitals worldwide.
ETHICS/DISSEMINATION: The OPTIMISE II trial has been approved by the UK National Research Ethics Service and has been approved by responsible ethics committees in all participating countries. The findings will be disseminated through publication in a widely accessible peer-reviewed scientific journal.
TRIAL REGISTRATION NUMBER: ISRCTN39653756.
PMID: 30647034 [PubMed - in process]
Protective Smell of Hydrogen Sulfide and Polysulfide in Cisplatin-Induced Nephrotoxicity.
Int J Mol Sci. 2019 Jan 14;20(2):
Authors: Cao X, Zhang W, Moore PK, Bian J
Though historically known as a toxic gas, hydrogen sulfide (H₂S) has displayed a new face as the third endogenous gaseous signaling molecule after nitric oxide (NO) and carbon monoxide (CO). Here in this review, we survey the role and therapeutic potential of H₂S in cisplatin-induced nephrotoxicity. Specifically, reduction of H₂S by cystathionine γ-lyase (CSE) downregulation upon cisplatin treatment may contribute to cisplatin-induced renal cell injury, possibly by augmentation of endogenous reactive oxygen species (ROS) production, while H₂S donation may prevent subsequent renal dysfunction by inhibiting NADPH oxidase activation. Intriguingly, H₂S slow-releasing compound GYY4137 seems to increase the anticancer activity of cisplatin, at least in several cancer cell lines, and this is probably due to its own anticancer effect. However, the efficacy of H₂S donors in tumor-bearing animals remains to be tested in terms of renal protection and cancer inhibition after receiving cisplatin. Furthermore, accumulative evidence regarding usage of polysulfide, a novel H₂S derived molecule, in the therapy of cisplatin-induced nephrotoxicity, was also summarized.
PMID: 30646560 [PubMed - in process]
Direct costs of low respiratory infection due to RSV in children under one year.
Rev Chil Pediatr. 2018 Aug;89(4):462-470
Authors: Zepeda T J, Vásquez Z J, Delpiano M L
INTRODUCTION: Considering the high prevalence of respiratory infections in hospitalized infants with Respiratory Syncytial Virus (RSV), the objective of this study is to determine the direct costs of this infection.
PATIENTS AND METHOD: Prospective longitudinal study in infants under one year of age hospitalized due to RSV during 2015. The patients were divided into 2 groups, Group 1 pa tients without risk factors and Group 2 patients with risk factors (prematurity, oxygen dependence, bronchopulmonary dysplasia, heart disease, immunocompromised patients), comparing each other variables such as nutritional status, gender, breastfeeding, discharge diagnosis, radiological diagno sis, length of hospital stay, among others. Direct costs for hospitalization were estimated according to the fees of the National Health Fund (FONASA) and the Modality of Institutional Care (MAI).
RESULTS: The total patients admitted in the period were 260: 234 (90%) in Group 1 and 26 (10%) in Group 2. The average hospital stay for Group 1 was 7.3 days (SD+5.1) with a median of 6 days, and 13.6 days (SD+16.3) for Group 2 with a median of 7 days (p < 0.05). The direct costs associated with RSV hospitalization were on average CLP $ 413,529 (US$ 632.1) for Group 1, and CLP $ 744,260 (US$ 1,137.6) for Group 2 (p < 0.05). There was also statistically significant higher cost for Group 2 due to tests and drugs (p < 0.05) and costs per day of hospital stay (p < 0.05).
CONCLUSION: These values, known for the first time in the national reality, confirm the high cost of these infections and particularly in risk groups.
PMID: 30571819 [PubMed - indexed for MEDLINE]
ACVIM consensus statement: Support for rational administration of gastrointestinal protectants to dogs and cats.
J Vet Intern Med. 2018 Nov;32(6):1823-1840
Authors: Marks SL, Kook PH, Papich MG, Tolbert MK, Willard MD
The gastrointestinal (GI) mucosal barrier is continuously exposed to noxious toxins, reactive oxygen species, microbes, and drugs, leading to the development of inflammatory, erosive, and ultimately ulcerative lesions. This report offers a consensus opinion on the rational administration of GI protectants to dogs and cats, with an emphasis on proton pump inhibitors (PPIs), histamine type-2 receptor antagonists (H2 RAs), misoprostol, and sucralfate. These medications decrease gastric acidity or promote mucosal protective mechanisms, transforming the management of dyspepsia, peptic ulceration, and gastroesophageal reflux disease. In contrast to guidelines that have been established in people for the optimal treatment of gastroduodenal ulcers and gastroesophageal reflux disease, effective clinical dosages of antisecretory drugs have not been well established in the dog and cat to date. Similar to the situation in human medicine, practice of inappropriate prescription of acid suppressants is also commonplace in veterinary medicine. This report challenges the dogma and clinical practice of administering GI protectants for the routine management of gastritis, pancreatitis, hepatic disease, and renal disease in dogs and cats lacking additional risk factors for ulceration or concerns for GI bleeding. Judicious use of acid suppressants is warranted considering recent studies that have documented adverse effects of long-term supplementation of PPIs in people and animals.
PMID: 30378711 [PubMed - indexed for MEDLINE]
Multiple part umbilical cord entanglement and neonatal outcomes.
Taiwan J Obstet Gynecol. 2018 Oct;57(5):672-676
Authors: Mariya T, Fujibe Y, Shinkai S, Sugita N, Suzuki M, Endo T, Saito T
OBJECTIVE: Umbilical cord entanglement is known to be a major cause of fetal hypoxia and to be correlated with several neonatal complications, but almost all of the previous reports were restricted to nuchal cord. In this study, we retrospectively examined the correlation between multiple part cord entanglement and pregnancy outcomes.
MATERIALS AND METHODS: A total of 2156 cases were recruited from term deliveries in our hospital from 2008 to 2012. We counted umbilical cord loop numbers not only for nuchal cord but also for trunk and limb cord entanglement. We classified the cases into three groups: no loop, single loop and multiple loops group. We statistically analyzed pregnancy outcomes statistically in the three groups.
RESULTS: One thousand, four hundred and fifty-eight cases had no cord entanglement, 594 cases had single loop entanglement and 104 cases had multiple loops entanglement. Values of umbilical artery blood, pH (p = 0.002) and base excess (p < 0.001) showed significantly unfavorable status in entanglement cases, especially in the multiple loops group. A significantly larger percentage of neonates in the multiple loops group needed for oxygen (p < 0.001).
CONCLUSION: Multiple umbilical cord entanglement is highly correlated with early neonatal unfavorable status and need for resuscitation.
PMID: 30342649 [PubMed - indexed for MEDLINE]
Rational modification of vanillin derivatives to stereospecifically destabilize sickle hemoglobin polymer formation.
Acta Crystallogr D Struct Biol. 2018 Oct 01;74(Pt 10):956-964
Authors: Deshpande TM, Pagare PP, Ghatge MS, Chen Q, Musayev FN, Venitz J, Zhang Y, Abdulmalik O, Safo MK
Increasing the affinity of hemoglobin for oxygen represents a feasible and promising therapeutic approach for sickle cell disease by mitigating the primary pathophysiological event, i.e. the hypoxia-induced polymerization of sickle hemoglobin (Hb S) and the concomitant erythrocyte sickling. Investigations on a novel synthetic antisickling agent, SAJ-310, with improved and sustained antisickling activity have previously been reported. To further enhance the biological effects of SAJ-310, a structure-based approach was employed to modify this compound to specifically inhibit Hb S polymer formation through interactions which perturb the Hb S polymer-stabilizing αF-helix, in addition to primarily increasing the oxygen affinity of hemoglobin. Three compounds, TD-7, TD-8 and TD-9, were synthesized and studied for their interactions with hemoglobin at the atomic level, as well as their functional and antisickling activities in vitro. X-ray crystallographic studies with liganded hemoglobin in complex with TD-7 showed the predicted mode of binding, although the interaction with the αF-helix was not as strong as expected. These findings provide important insights and guidance towards the development of molecules that would be expected to bind and make stronger interactions with the αF-helix, resulting in more efficacious novel therapeutics for sickle cell disease.
PMID: 30289405 [PubMed - indexed for MEDLINE]
Optimal drainage cannula position in dual cannulation for veno-venous extracorporeal membrane oxygenation.
Int J Artif Organs. 2018 Dec;41(12):867-871
Authors: Togo K, Takewa Y, Katagiri N, Fujii Y, Yamashita AC, Tastumi E
INTRODUCTION:: Recently, the use of veno-venous extracorporeal membrane oxygenation for adult patients with severe acute respiratory failure has increased. We previously investigated the optimal return cannula position; however, the optimal drainage cannula position has not yet been fully clarified. The aim of this study was to investigate the optimal drainage cannula position.
METHODS:: Veno-venous extracorporeal membrane oxygenation was performed in four adult goats (mean body weight 59.6 ± 0.6 kg). The position of the drainage cannula was varied among the right atrium, the upper inferior vena cava, and the lower inferior vena cava, whereas the position of the return cannula was fixed in the superior vena cava. The recirculation fraction and arterial oxygen saturation and pressure (SaO2, PaO2) were measured in all drainage cannula positions.
RESULTS:: In the lower inferior vena cava drainage cannula position, the recirculation fraction was the lowest. In the lower inferior vena cava, upper inferior vena cava, and right atrium drainage cannula positions at 3 L/min, SaO2 and PaO2 after 20 min were 92.9% ± 4.9% and 75.1 ± 26.0 mm Hg, 99.5% ± 0.5% and 113.8 ± 20.9 mm Hg, and 93.8% ± 6.2% and 91.9 ± 17.7 mm Hg, respectively.
CONCLUSION:: With respect to blood oxygenation, the optimal position for the drainage cannula was the upper inferior vena cava. These findings suggested that blood from the superior vena cava, inferior vena cava, and hepatic vein was most efficiently drained in the upper inferior vena cava cannula position.
PMID: 30223702 [PubMed - indexed for MEDLINE]
Adenosine A2A receptor antagonists act at the hyperoxic phase to confer protection against retinopathy.
Mol Med. 2018 07 31;24(1):41
Authors: Zhou R, Zhang S, Gu X, Ge Y, Zhong D, Zhou Y, Tang L, Liu XL, Chen JF
BACKGROUND: Retinopathy of prematurity (ROP) remains a major cause of childhood blindness and current laser photocoagulation and anti-VEGF antibody treatments are associated with reduced peripheral vision and possible delayed development of retinal vasculatures and neurons. In this study, we advanced the translational potential of adenosine A2A receptor (A2AR) antagonists as a novel therapeutic strategy for selectively controlling pathological retinal neovascularization in oxygen-induced retinopathy (OIR) model of ROP.
METHODS: Developing C57BL/6 mice were exposed to 75% oxygen from postnatal (P) day 7 to P12 and to room air from P12 to P17 and treated with KW6002 or vehicle at different postnatal developmental stages. Retinal vascularization was examined by whole-mount fluorescence and cross-sectional hematoxylin-eosin staining. Cellular proliferation, astrocyte and microglial activation, and tip cell function were investigated by isolectin staining and immunohistochemistry. Apoptosis was analyzed by TUNEL assay. The effects of oxygen exposure and KW6002 treatment were analyzed by two-way ANOVA or Kruskal-Wallis test or independent Student's t-test or Mann-Whitney U test.
RESULTS: The A2AR antagonist KW6002 (P7-P17) did not affect normal postnatal development of retinal vasculature, but selectively reduced avascular areas and neovascularization, with the reduced cellular apoptosis and proliferation, and enhanced astrocyte and tip cell functions in OIR. Importantly, contrary to our prediction that A2AR antagonists were most effective at the hypoxic phase with aberrantly increased adenosine-A2AR signaling, we discovered that the A2AR antagonist KW6002 mainly acted at the hyperoxic phase to confer protection against OIR as KW6002 treatment at P7-P12 (but not P12-P17) conferred protection against OIR; this protection was observed as early as P9 with reduced avascular areas and reduced cellular apoptosis and reversal of eNOS mRNA down-regulation in retina of OIR.
CONCLUSIONS: As ROP being a biphasic disease, our identification of the hyperoxic phase as the effective window, together with selective and robust protection against pathological (but not physiological) angiogenesis, elevates A2AR antagonists as a novel therapeutic strategy for ROP treatment.
PMID: 30134834 [PubMed - indexed for MEDLINE]
Reactive Oxygen Species Mediate Therapeutic Ultrasound-Induced, Mitogen-Activated Protein Kinase Activation in C28/I2 Chondrocytes.
Ultrasound Med Biol. 2018 10;44(10):2105-2114
Authors: Kaur H, Siraki AG, Sharma M, Uludağ H, Dederich DN, Flood P, El-Bialy T
Low-intensity pulsed ultrasound (LIPUS) has been used for the treatment of non-healing fractures because of its therapeutic properties of stimulating enhancing endochondral bone formation. However, its mechanism of action remains unclear. In this study, we hypothesized that LIPUS activates mitogen-activated protein kinases through generation of reactive oxygen species. C28/I2 cells were stimulated with LIPUS for 10 and 20 min, while the control group was treated using a sham LIPUS transducer. Through quantitative reverse transcription polymerase chain reaction and immunoblot analyses, we determined that LIPUS application increased reactive oxygen species generation and cell viability in C28/I2 cells. There were increases in the phosphorylation level of ERK1/2 and in expression of SOX9, COL2 A1 and ACAN genes. These effects were reversed when cells were treated with diphenylene iodonium, which is known to inhibit NADPH oxidase. It was concluded that exposure of chondrocytes to LIPUS led to reactive oxygen species generation, which activated MAPK signaling and further increased chondrocyte-specific gene markers involved in chondrocyte differentiation and extracellular matrix formation.
PMID: 30037475 [PubMed - indexed for MEDLINE]
sFasL-mediated induction of neutrophil activation in patients with type 2 diabetes mellitus.
PLoS One. 2018;13(7):e0201087
Authors: Margaryan S, Witkowicz A, Arakelyan A, Partyka A, Karabon L, Manukyan G
Fas/Fas ligand system was shown to be related to insulin resistance and type 2 diabetes mellitus (T2DM). However, the role of soluble Fas ligand (sFasL) in functioning of immune cells in type 2 diabetes mellitus (T2DM) has not been studied yet. The aim of the present study was to determine in vitro effects of sFasL on neutrophil activation and apoptosis. We demonstrate here that sFasL exhibited proinflammatory effect and induced mRNA levels of caspase-1, NF-κB, IL-1β and CD18 expression. At the same time, sFasL induced reactive oxygen species (ROS) production. Activation of caspase-1 activity abolished sFasL-dependent apoptosis, and suppressed Fas expression and mRNA levels of caspase-3 in neutrophils from T2DM patients. Collectively, our findings identify a novel proinflammatory role of sFasL in T2DM neutrophils that is dependent of caspase activity. Thus, sFasL enhances inflammatory response of neutrophils from T2DM patients without increasing apoptosis suggesting its triggering role in T2DM inflammation.
PMID: 30024959 [PubMed - indexed for MEDLINE]
Feasibility and effects of intra-dialytic low-frequency electrical muscle stimulation and cycle training: A pilot randomized controlled trial.
PLoS One. 2018;13(7):e0200354
Authors: McGregor G, Ennis S, Powell R, Hamborg T, Raymond NT, Owen W, Aldridge N, Evans G, Goodby J, Hewins S, Banerjee P, Krishnan NS, Ting SMS, Zehnder D
BACKGROUND AND OBJECTIVES: Exercise capacity is reduced in chronic kidney failure (CKF). Intra-dialytic cycling is beneficial, but comorbidity and fatigue can prevent this type of training. Low-frequency electrical muscle stimulation (LF-EMS) of the quadriceps and hamstrings elicits a cardiovascular training stimulus and may be a suitable alternative. The main objectives of this trial were to assess the feasibility and efficacy of intra-dialytic LF-EMS vs. cycling.
DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Assessor blind, parallel group, randomized controlled pilot study with sixty-four stable patients on maintenance hemodialysis. Participants were randomized to 10 weeks of 1) intra-dialytic cycling, 2) intra-dialytic LF-EMS, or 3) non-exercise control. Exercise was performed for up to one hour three times per week. Cycling workload was set at 40-60% oxygen uptake (VO2) reserve, and LF-EMS at maximum tolerable intensity. The control group did not complete any intra-dialytic exercise. Feasibility of intra-dialytic LF-EMS and cycling was the primary outcome, assessed by monitoring recruitment, retention and tolerability. At baseline and 10 weeks, secondary outcomes including cardio-respiratory reserve, muscle strength, and cardio-arterial structure and function were assessed.
RESULTS: Fifty-one (of 64 randomized) participants completed the study (LF-EMS = 17 [77%], cycling = 16 [80%], control = 18 [82%]). Intra-dialytic LF-EMS and cycling were feasible and well tolerated (9% and 5% intolerance respectively, P = 0.9). At 10-weeks, cardio-respiratory reserve (VO2 peak) (Difference vs. control: LF-EMS +2.0 [95% CI, 0.3 to 3.7] ml.kg-1.min-1, P = 0.02, and cycling +3.0 [95% CI, 1.2 to 4.7] ml.kg-1.min-1, P = 0.001) and leg strength (Difference vs. control: LF-EMS, +94 [95% CI, 35.6 to 152.3] N, P = 0.002 and cycling, +65.1 [95% CI, 6.4 to 123.8] N, P = 0.002) were improved. Arterial structure and function were unaffected.
CONCLUSIONS: Ten weeks of intra-dialytic LF-EMS or cycling improved cardio-respiratory reserve and muscular strength. For patients who are unable or unwilling to cycle during dialysis, LF-EMS is a feasible alternative.
PMID: 29995947 [PubMed - indexed for MEDLINE]
Curcumin attenuates cerebral ischemia injury in Sprague-Dawley rats and PC12 cells by suppressing overactivated autophagy.
J Photochem Photobiol B. 2018 Jul;184:1-6
Authors: Zhang Y, Fang M, Sun Y, Zhang T, Shi N, Li J, Jin L, Liu K, Fu J
The present study assessed whether the protective effects of curcumin against cerebral ischemia injury were due to the suppression of overactivated autophagy. Curcumin is a well-known natural polyphenolic compound that effectively counteracts oxidation, inflammation, and various types of cancer. Several studies have demonstrated the protective effects of curcumin against ischemia-reperfusion injury in tissues from the lungs, cardiomyocytes, and liver. The present study employed brain injury models induced by middle cerebral artery occlusion (MCAO) in rats and PC12 oxygen-glucose-deprived (OGD) cells. Infarct area, neurological score, lactate dehydrogenase (LDH) activity, autophagy expression, cell apoptosis, and mRNA and protein expressions of caspase-3 were determined following curcumin supplementation. Compared to MCAO rats, curcumin-treated MCAO rats exhibited substantial reductions in neurological score, infarct area, and LDH activity. MCAO also increased LC3 II/I protein expression and decreased p62 protein expression, but curcumin supplementation significantly reversed these altered protein expressions. Caspase-3 protein expression increased by 46.2% in the MCAO group, but curcumin supplementation significantly reduced this expression. Similarly, apoptosis increased by 33.1% in OGD cells, but curcumin supplementation significantly reduced apoptosis to 21.6% and 9.3% at doses of 100 and 200 mg/kg, respectively. The mRNA and protein expressions of caspase-3 exhibited substantial increases in OGD cells but these expressions were significantly decreased following curcumin supplementation. Taken together, the present results indicate that curcumin represents a natural bioactive substance that can protect against cerebral ischemia via the suppression of overactivated autophagy.
PMID: 29777940 [PubMed - indexed for MEDLINE]
Cold Plasmas for Biofilm Control: Opportunities and Challenges.
Trends Biotechnol. 2018 06;36(6):627-638
Authors: Gilmore BF, Flynn PB, O'Brien S, Hickok N, Freeman T, Bourke P
Bacterial biofilm infections account for a major proportion of chronic and medical device associated infections in humans, yet our ability to control them is compromised by their inherent tolerance to antimicrobial agents. Cold atmospheric plasma (CAP) represents a promising therapeutic option. CAP treatment of microbial biofilms represents the convergence of two complex phenomena: the production of a chemically diverse mixture of reactive species and intermediates, and their interaction with a heterogeneous 3D interface created by the biofilm extracellular polymeric matrix. Therefore, understanding these interactions and physiological responses to CAP exposure are central to effective management of infectious biofilms. We review the unique opportunities and challenges for translating CAP to the management of biofilms.
PMID: 29729997 [PubMed - indexed for MEDLINE]
The potential of zwitterionic nanoliposomes against neurotoxic alpha-synuclein aggregates in Parkinson's Disease.
Nanoscale. 2018 May 17;10(19):9174-9185
Authors: Aliakbari F, Mohammad-Beigi H, Rezaei-Ghaleh N, Becker S, Dehghani Esmatabad F, Eslampanah Seyedi HA, Bardania H, Tayaranian Marvian A, Collingwood JF, Christiansen G, Zweckstetter M, Otzen DE, Morshedi D
The protein α-synuclein (αSN) aggregates to form fibrils in neuronal cells of Parkinson's patients. Here we report on the effect of neutral (zwitterionic) nanoliposomes (NLPs), supplemented with cholesterol (NLP-Chol) and decorated with PEG (NLP-Chol-PEG), on αSN aggregation and neurotoxicity. Both NLPs retard αSN fibrillization in a concentration-independent fashion. They do so largely by increasing lag time (formation of fibrillization nuclei) rather than elongation (extension of existing nuclei). Interactions between neutral NLPs and αSN may locate to the N-terminus of the protein. This interaction can even perturb the interaction of αSN with negatively charged NLPs which induces an α-helical structure in αSN. This interaction was found to occur throughout the fibrillization process. Both NLP-Chol and NLP-Chol-PEG were shown to be biocompatible in vitro, and to reduce αSN neurotoxicity and reactive oxygen species (ROS) levels with no influence on intracellular calcium in neuronal cells, emphasizing a prospective role for NLPs in reducing αSN pathogenicity in vivo as well as utility as a vehicle for drug delivery.
PMID: 29725687 [PubMed - indexed for MEDLINE]
Cold Atmospheric Plasmas: A Novel and Promising Way to Treat Neurological Diseases.
Trends Biotechnol. 2018 06;36(6):582-583
Authors: Xiong Z
Cold atmospheric plasmas (CAPs) can enhance neural cell differentiation into neurons both in vitro and in vivo, which is of great interest for medical treatment of neurodegenerative diseases like Alzheimer's disease and traumatic injuries of the central nervous system. CAPs represent a promising method for future neurological disease therapy.
PMID: 29685819 [PubMed - indexed for MEDLINE]
Influence of exercise on oxidative stress in patients with heart failure.
Heart Fail Rev. 2018 03;23(2):225-235
Authors: Sties SW, Andreato LV, de Carvalho T, Gonzáles AI, Angarten VG, Ulbrich AZ, de Mara LS, Netto AS, da Silva EL, Andrade A
Reactive oxygen species play an important role in the pathophysiology of heart failure (HF). In contrast, regular physical exercise can promote adaptations to reactive oxygen species that are beneficial for patients with HF. We completed a systematic review of randomized controlled trials that evaluate the influence of exercise on oxidative stress in patients with HF. Articles were searched in the PubMed, Cochrane, SciELO, and LILACS databases. The search was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The quality of the included studies was assessed using the Physiotherapy Evidence Database scale. We selected 12 studies with a total of 353 participants. The included patients had a left ventricle ejection fraction of < 52% and New York Heart Association functional class II or III disease. A significant increase was observed in peak oxygen consumption (between 10 and 46%) in the group that underwent training (TG). There was an improvement in the oxidative capacity of skeletal muscles in the TG, related to the positive activity of mitochondrial cytochrome c oxidase (between 27 and 41%). An increase in the expression of the enzymes glutathione peroxidase (41%), catalase (between 14 and 42%), and superoxide dismutase (74.5%), and a decrease in lipid peroxidation (between 28.8 and 58.5%) were observed in the TG. Physical training positively influenced the cardiorespiratory capacity and enhanced the benefits of oxidant and antioxidant biomarkers in patients with HF. High-intensity training promoted a 15% increase in the plasma total antioxidant capacity, whereas moderate training had no effect.
PMID: 29497889 [PubMed - indexed for MEDLINE]
Protective Effects of Indian Spice Curcumin Against Amyloid-β in Alzheimer's Disease.
J Alzheimers Dis. 2018;61(3):843-866
Authors: Reddy PH, Manczak M, Yin X, Grady MC, Mitchell A, Tonk S, Kuruva CS, Bhatti JS, Kandimalla R, Vijayan M, Kumar S, Wang R, Pradeepkiran JA, Ogunmokun G, Thamarai K, Quesada K, Boles A, Reddy AP
The purpose of our article is to assess the current understanding of Indian spice, curcumin, against amyloid-β (Aβ)-induced toxicity in Alzheimer's disease (AD) pathogenesis. Natural products, such as ginger, curcumin, and gingko biloba have been used as diets and dietary supplements to treat human diseases, including cancer, cardiovascular, respiratory, infectious, diabetes, obesity, metabolic syndromes, and neurological disorders. Products derived from plants are known to have protective effects, including anti-inflammatory, antioxidant, anti-arthritis, pro-healing, and boosting memory cognitive functions. In the last decade, several groups have designed and synthesized curcumin and its derivatives and extensively tested using cell and mouse models of AD. Recent research on Aβ and curcumin has revealed that curcumin prevents Aβ aggregation and crosses the blood-brain barrier, reach brain cells, and protect neurons from various toxic insults of aging and Aβ in humans. Recent research has also reported that curcumin ameliorates cognitive decline and improves synaptic functions in mouse models of AD. Further, recent groups have initiated studies on elderly individuals and patients with AD and the outcome of these studies is currently being assessed. This article highlights the beneficial effects of curcumin on AD. This article also critically assesses the current limitations of curcumin's bioavailability and urgent need for new formulations to increase its brain levels to treat patients with AD.
PMID: 29332042 [PubMed - indexed for MEDLINE]
Retrospective Consent in a Neonatal Randomized Controlled Trial.
Pediatrics. 2018 01;141(1):
Authors: Songstad NT, Roberts CT, Manley BJ, Owen LS, Davis PG, HIPSTER trial investigators
BACKGROUND AND OBJECTIVES: The requirement for prospective consent in clinical trials in acute settings may result in samples unrepresentative of the study population, potentially altering study findings. However, using retrospective consent may raise ethical issues. We assessed whether using retrospective consent affected recruitment, participant characteristics, and outcomes within a randomized controlled trial.
METHODS: We conducted a secondary analysis of a randomized trial, which compared nasal high flow (nHF) with nasal continuous positive airway pressure (CPAP) for primary respiratory support in preterm infants. In Era 1, all infants were consented prospectively; in Era 2, retrospective consent was available. We assessed inclusion rates of eligible infants, demographic data, and primary trial outcome (treatment failure within 72 hours).
RESULTS: In Era 1, recruitment of eligible infants was lower than in Era 2: 111 of 220 (50%) versus 171 of 209 (82%), P < .001; intrapartum antibiotic administration was lower: 23 of 111 (21%) versus 84 of 165 (51%), P < .001; full courses of antenatal steroids were higher: 86 of 111 (78%) versus 103 of 170 (61%), P = .004; and more infants received pre-randomization CPAP: 77 of 111 (69%) versus 48 of 171 (28%), P < .001. In Era 1, nHF failure (15 of 56, 27%) and CPAP failure (14 of 55, 26%) rates were similar, P = .9. In Era 2, failure rates differed: 24 of 85 (28%) nHF infants versus 13 of 86 (15%) CPAP infants, P = .04. The χ2 interaction test was nonsignificant (P = .20).
CONCLUSIONS: The use of retrospective consent resulted in greater recruitment and differences in risk factors between eras. Using retrospective consent altered the study sample, which may be more representative of the whole population. This may improve scientific validity but requires further ethical evaluation.
PMID: 29288162 [PubMed - indexed for MEDLINE]
Are Contact Lens Discomfort or Soft Contact Lens Material Properties Associated with Alterations in the Corneal Sub-Basal Nerve Plexus?
Curr Eye Res. 2018 04;43(4):487-492
Authors: López-De La Rosa A, Arroyo-Del Arroyo C, Cañadas P, López-Miguel A, Calonge M, Enríquez-De-Salamanca A, González-García MJ
PURPOSE: To study whether contact lens (CL) discomfort and some properties of soft CL materials are associated with alterations in the nerve fibers morphology and density of dendritic cells of the corneal sub-basal nerve plexus.
MATERIALS AND METHODS: Forty soft CL wearers and 20 non-CL wearers were included. The Contact Lens Dry Eye Questionnaire-short form was administered to divide CL wearers based on their symptoms (20 symptomatic and 20 asymptomatic CL wearers were included). The CL material properties considered were the CL material type (16 hydrogel and 24 silicone hydrogel CL wearers were included), water content, oxygen transmissibility, and modulus of elasticity. Confocal microscopy was performed, and the number and density of corneal nerves, density of nerve branches, grade of nerve tortuosity, and density of dendritic cells were analyzed. The effects of CL discomfort and CL material properties on the confocal microscopy parameters were analyzed.
RESULTS: No significant differences were found among symptomatic and asymptomatic CL wearers and non-CL wearers in any of the confocal microscopy parameters evaluated. The density of dendritic cells was higher in the hydrogel CL wearers compared to the silicone hydrogel CL wearers and non-CL wearers (p = 0.002). The density of dendritic cells tended to be higher as the oxygen transmissibility decreased (β = -0.40, p = 0.07).
CONCLUSIONS: CL discomfort appears not to be associated with alterations in the corneal sub-basal nerve plexus. Hydrogel CL wear might be involved in the recruitment of dendritic cells into the cornea, being a possible origin its lower oxygen permeability compared to silicone hydrogel materials. Future studies are required to confirm these results.
PMID: 29286836 [PubMed - indexed for MEDLINE]
Plasmas for Treating Cancer: Opportunities for Adaptive and Self-Adaptive Approaches.
Trends Biotechnol. 2018 06;36(6):586-593
Authors: Keidar M, Yan D, Beilis II, Trink B, Sherman JH
Plasma is an ionized gas that is typically formed under high-temperature laboratory conditions. Recent progress in atmospheric plasmas has led to cold atmospheric plasma (CAP) devices with ion temperatures close to room temperature. The unique chemical and physical properties of CAP have led to its use in various biomedical applications including cancer therapy. CAP exhibits a spontaneous transition from a spatially homogeneous state to a modifiable pattern that is subject to self-organization. In this Opinion article, we discuss some new applications for plasma in cancer therapy based on plasma self-organization, which enables adaptive features in plasma-based therapeutic systems.
PMID: 28755977 [PubMed - indexed for MEDLINE]