Human Pilot Study Research Articles

A Safety and Effectiveness Evaluation of a Callus Softener Containing Potassium Hydroxide.

Limited safety information has been described in the peer-reviewed literature for callus-softening products containing potassium hydroxide. This pilot human use study evaluated the safety and effectiveness of a commercially available callus softener, containing less than 10% potassium hydroxide by weight. Baseline callused skin was scored (grade 1-4) on each study participant's feet (n = 10). Participants' feet were soaked and then a licensed manicurist applied a callus softener product to the right foot, which remained on callused skin for 3 to 5 minutes (no callus softener was applied to the participant's left foot). Both feet were then wiped with a wet towel, and a foot rasp was used to file the callused skin, beginning on the left foot. Callused skin was scored and participants' feet were evaluated by a physician immediately after use, 1 day after use, and 1 week after use for the presence or absence of skin irritation, adverse skin reactions, and chemical burns. No adverse events were reported by study participants or the physician for all evaluation time points. Each participant's highest callus grade score on the treated foot either improved or remained the same following product use (compared to baseline). Mean callus grade scores were 1.75 at baseline, 1.55 immediately after use, 1.25 1 day after use, and 1.50 1 week after use. Results from this pilot study suggest that callus-softening products containing less than 10% potassium hydroxide are likely to be safe and effective products under intended use scenarios of 3- to 5-minute application times, as dictated by product label instructions.

Assessing the antioxidant and metabolic effect of an alpha-lipoic acid and acetyl-L-carnitine nutraceutical

Personalized nutrition (PN) is seen as a potentially effective and affordable strategy for the prevention of non-communicable diseases (NCDs). In this study we aimed to evaluate the antioxidant and metabolic effect of a dietary supplement based on alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALC) in order to include this product in a novel PN service. The antioxidant properties of the commercial nutraceutical were investigated at physiological conditions (through in vitro digestion) and at mitochondrial conditions. The metabolic activity was assessed in a human pilot study using a Gas Chromatography-Mass Spectrometry (GC-MS) methodology in dried urine samples. The nutraceutical exerted an elevated antiradical activity and reducing capacity, especially at mitochondrial conditions, after in vitro digestion. This increase in mitochondrial activity was also evidenced in vivo by a significant increase in the urinary phosphate concentration (p ​= ​0.004). As pro-oxidant effect was reached with the concentration of 4 capsules, 2 capsules at the same time could be a reasonable dose. No adverse effects were recorded in vivo with this dose. Thus, although its metabolic effect was not so conclusive, ALA ​+ ​ALC combination might be beneficial as a dietary supplement for the prevention of the oxidative stress and an interesting dietary supplement to consider in large scale studies.

A Pilot Study of an Innovative Model of Care Delivery: Service Robot for Older People with Dementia in a Rural Community

Background: The telehealth approach offers enhanced service delivery for older patients living in rural areas. Purpose: We conducted a pilot study to evaluate the feasibility of using the Zenbo robot to improve the quality of care of elderly individuals with dementia. Methodology: In this study, we developed a digital solution on service robots and smart devices, which can leverage the capacity of the user-friendly interactive interface and digital dialog system. A group of eleven volunteered older adults was selected for this study. To assess the likability and acceptance of the Zenbo, we conducted a one-on-one (robot vs human) pilot study in our long-term care stations. Each participant engaged in conversational interactions for five consecutive days and completed a survey of 12 questions about the experiences they had with the Zenbo, at the beginning and the end of the study respectively. Results: Subjects with lower GDS-15 scores have more positive attitudes toward the robot before the intervention. 27% of older adults had an increase in positive attitudes toward the interaction with the Zenbo robot. With the aid of teleoperated mobile robotic systems at home, the innovative service model can be achieved through telecommunication between primary health professionals or caregivers at remote locations and psychiatrists at the medical center to make the seamless care environment real. Conclusion: The IoT technologies can be used to assist physicians in switching from a hospital-centered model of care to a home-based service for older people with dementia. It merits more future clinical trials and usability tests.

Hypoxia and hypercapnia effects on cerebral oxygen saturation in avalanche burial: A pilot human experimental study

BackgroundA sufficient supply of oxygen is crucial to avoid hypoxic cardiac arrest and brain damage within 30 min in completely-buried avalanche victims. Snow density influences levels of hypoxia and hypercapnia. The goal of this study was to investigate the effects of hypoxia and hypercapnia on cerebral oxygenation (ScO2) in humans breathing into an artificial air pocket. MethodsEach subject breathed into a closed system (air-tight face mask – plastic tube – snow air-pocket of 4 L) up to 30 min. Each subject performed three tests in different snow densities. ScO2 was measured by a near-infrared spectroscopy (NIRS) device. Measurements included peripheral oxygen saturation (SpO2), end-tidal carbon dioxide (ETCO2), air pocket gases and blood gases. Snow density was assessed via standard methods and micro-computed tomography. Based on predetermined criteria, tests were classified based on whether they were terminated before 30 min and the reason for termination. The categories were: completed tests (30 min), tests terminated before 30 min when SpO2 dropped to ≤75% and tests that were terminated before 30 min by requests of the subjects. General linear models were used to compare termination groups for changes in ScO2, ETCO2, SpO2 and air pocket gases, and a multivariate analysis was used to detect factor independent effects on ScO2. ResultsScO2 was decreased in the group in which the tests were terminated for SpO2 ≤ 75% caused by a decrease in oxygen supply in high snow densities. In the completed tests, an increase in ScO2 occurred despite decreased oxygen supply and decreased carbon dioxide removal. ConclusionsOur data show that ScO2 determined by NIRS was not always impaired in humans breathing into an artificial air pocket despite decreased oxygen supply and decreased carbon dioxide removal. This may indicate that in medium to low snow densities brain oxygenation can be sufficient, which may reflect the initial stage of the triple H (hypothermia, hypoxia, and hypercapnia) syndrome. In high snow densities, ScO2 showed a significant decrease caused by a critical decrease in oxygen supply. This could lead to a higher risk of hypoxic cardiac arrest and brain damage.

A bioelectric neural interface towards intuitive prosthetic control for amputees

Objective. While prosthetic hands with independently actuated digits have become commercially available, state-of-the-art human-machine interfaces (HMI) only permit control over a limited set of grasp patterns, which does not enable amputees to experience sufficient improvement in their daily activities to make an active prosthesis useful. Approach. Here we present a technology platform combining fully-integrated bioelectronics, implantable intrafascicular microelectrodes and deep learning-based artificial intelligence (AI) to facilitate this missing bridge by tapping into the intricate motor control signals of peripheral nerves. The bioelectric neural interface includes an ultra-low-noise neural recording system to sense electroneurography (ENG) signals from microelectrode arrays implanted in the residual nerves, and AI models employing the recurrent neural network (RNN) architecture to decode the subject’s motor intention. Main results. A pilot human study has been carried out on a transradial amputee. We demonstrate that the information channel established by the proposed neural interface is sufficient to provide high accuracy control of a prosthetic hand up to 15 degrees of freedom (DOF). The interface is intuitive as it directly maps complex prosthesis movements to the patient’s true intention. Significance. Our study layouts the foundation towards not only a robust and dexterous control strategy for modern neuroprostheses at a near-natural level approaching that of the able hand, but also an intuitive conduit for connecting human minds and machines through the peripheral neural pathways.Clinical trial: DExterous Hand Control Through Fascicular Targeting (DEFT). Identifier: NCT02994160.

Sweat and saliva cortisol response to stress and nutrition factors

Cortisol is a biomarker for stress monitoring; however, the biomedical and clinical relevance is still controversial due to the complexity of cortisol secretion mechanisms and their circadian cycles as well as environmental factors that affect physiological cortisol level, which include individual mood and dietary intake. To further investigate this multifaceted relationship, a human pilot study examined cortisol concentration in sweat and saliva samples collected from 48 college-aged participants during aerobic exercise sessions along with mental distress and nutrition surveys. Enzyme-linked immunosorbent assays determined highly significant differences between apocrine-dominant sweat (AP), saliva before exercise (SBE), and saliva after exercise (SAE) cortisol concentration (AP-SBE: p = 0.0017, AP-SAE: p = 0.0102). A significantly greater AP cortisol concentration was detected in males compared to females (p = 0.0559), and significant SAE cortisol concentration differences were also recorded between recreational athletes and non-athletes (p = 0.044). However, Kessler 10 Psychological Distress Scale (K10) scores, an examination administered to deduce overall wellness, provided no significant differences between males and females or athletes and non-athletes in distress levels, which statistically signifies a direct relationship to cortisol was not present. For further analysis, dietary intake from all participants was considered to investigate whether a multiplexed association was prevalent between nutrition, mood, and cortisol release. Significant positive correlations between AP cortisol, SAE cortisol, K10 scores, and fat intake among female participants and athletes were discovered. The various machine learning algorithms utilized the extensive connections between dietary intake, overall well-being, sex factors, athletic activity, and cortisol concentrations in various biofluids to predict K10 scores. Indeed, the understanding of physiochemical stress response and the associations between studied factors can advance algorithm developments for cortisol biosensing systems to mitigate stress-based illnesses and improve an individual’s quality of life.

In Utero Glyphosate Exposure and Anogenital Distance in Newborns from The Infant Development and Environment Study (TIDES)

Background: Human exposure to glyphosate has become ubiquitous as its presence in the environment rises. Recent studies have described some endocrine disrupting effects of glyphosate. Specifically, in our work in rodents we observed an association between gestational exposure to low-dose glyphosate and Roundup® (a glyphosate-based herbicide) and longer anogenital distance (AGD), a marker of the prenatal hormone milieu, in male and female pups, suggesting an androgenic effect. In this pilot human study, we examined relation between in utero glyphosate exposure and newborn AGD. Methods: We measured glyphosate and its degradation product aminomethylphosphonic acid (AMPA) in 2nd trimester maternal urine from 100 pregnant women from the TIDES cohort (50 females and 50 males). Study staff obtained two measures of AGD; the anopenile and anoscrotal distances (males) and the anoclitoral and anofourchette distances (females). We used the median glyphosate and AMPA concentration to classify subjects into low and high exposure. The relation between exposure and AGD was evaluated using sex-stratified multivariable linear regression adjusted for age at exam, weight-for-length Z-scores, study center, gestational age, maternal age and urine collection time. Results: Glyphosate and AMPA concentrations were above the limits of detection in 95% and 93% of the samples, respectively. Glyphosate and AMPA urinary concentrations were highly correlated (r=0.57, P=7.6x10-10), with glyphosate levels (median, 0.23 ng/mL) higher than AMPA (median, 0.15 ng/mL). High (above median) glyphosate and AMPA were both statistically significantly (P<0.05) associated with increased AGD in females. In males, associations were also positive, but weaker and non-significant. Conclusion: These preliminary findings demonstrate measurable glyphosate exposure in the general population, and suggest a link between in utero glyphosate exposure and longer AGD particularly in females. Given the increasing glyphosate exposure in the US population and its potential role as an endocrine disruptor, this prevalent exposure warrants evaluation in larger studies.

Thread-based multiplexed sensor patch for real-time sweat monitoring

Sensor platforms that exploit the fibrous textile threads as substrates offer great promise since they can be directly sewn, woven or stitched on to any clothing. They can also be placed directly in intimate contact with the skin. In this work, we present a thread-based sensing platform in the form of a multiplexed sensing patch for continuous simultaneous on-skin monitoring of sweat. The patch performs real-time, on-body measurements of important biomarkers present in sweat such as electrolytes (sodium and ammonium ions), metabolites (lactate) and acidity (pH). Flexible threads coated with conductive inks were used as sensing electrodes. Selective potentiometric detection of electrolytes and pH was made possible through ion-selective membrane deposition and pH-sensitive polyaniline coating on threads, respectively. An amperometric enzymatic sensing scheme with lactate oxidase was used for the detection of lactate. An array of the thread sensors is integrated onto a patch with connectivity to a miniaturized circuit module containing a potentiostat, microprocessor and wireless circuitry for wireless smartphone readout. Extensive in vitro validation and an in vivo human pilot study involving a maximal exertion test show the promise of this platform for real-time physiological monitoring of human performance/fitness under stress, as well as diagnostic monitoring through sweat analysis.

Atelocollagen Application in Human Periodontal Tissue Treatment-A Pilot Study.

Background: The aim of this study is the clinical observation of gingival tissue condition after atelocollagen injection. Methods: In 18 patients, 97 gingival class I Miller recessions were divided according to recession height, gingival papillae loss and thickness of gingivae. Atelocollagen (Linerase, 100 mg) was injected into keratinized gingivae twice or thrice, at two-week intervals. Results: Statistically significant changes in gingival recession, amount of gingival papillae loss and thickness of gingiva were observed, after both two and three collagen injections. Although the degree (height) of recession decreased and gingival tissue thickness increased with every injection; there was no difference in gingival papillae loss between second and third collagen injections. Conclusions: The injectable form of atelocollagen is a promising material for gingival soft tissue regeneration and stimulation and allows for reduction in the number of procedures and support in a variety of surgical scenarios. This is a pilot study that clinically measures the impact of injected atelocollagen on periodontal tissue biotype, including the thickness of gingivae and gingival papillae regeneration.

Modulation of H-reflex responses and frequency-dependent depression by repetitive spinal electromagnetic stimulation: From rats to humans and back to chronic spinal cord injured rats.

The lack of propagation of signals through survived fibers is among the major reasons for functional loss after incomplete spinal cord injury (SCI). Our recent results of animal studies demonstrate that spinal electromagnetic stimulation (SEMS) can enhance transmission in damaged spinal cord, and this type of modulation depends on the function of NMDA receptors at the neuronal networks below the injury level. Here, our pilot human study revealed that administration of repetitive SEMS induced long‐lasting modulation of H‐responses in both healthy and participants with chronic SCI. In order to understand the mechanisms underlying these effects, we have used an animal model and examined effects of SEMS on H‐responses. Effects of SEMS on H‐responses, frequency‐dependent depression (FDD) of H‐reflex, and possible underlying mechanisms have been examined in both naïve and rats with SCI. Our results demonstrate that consistent with the effects of SEMS on H‐reflex seen in humans, repetitive SEMS induced similar modulation in excitability of peripheral nerve responses in both non‐injured and rats with SCI. Importantly, our results confirmed the reduced FDD of H‐reflex in SCI animals and revealed that SEMS was able to recover FDD in rats with chronic SCI. Using intraspinal injections of the NMDA receptor blocker MK‐801, we have identified NMDA receptors as an important contributor to these SEMS‐induced effects in rats with SCI. These results identify SEMS as a novel non‐invasive technique for modulation of neuro‐muscular circuits and, importantly, modulation of spinal networks after chronic SCI.

Bis(monoacylglycero)phosphate, a new lipid signature of endosome-derived extracellular vesicles

Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid (LBPA), is a phospholipid specifically enriched in the late endosome-lysosome compartment playing a crucial role for the fate of endocytosed components. Due to its presence in extracellular fluids during diseases associated with endolysosomal dysfunction, it is considered as a possible biomarker of disorders such as genetic lysosomal storage diseases and cationic amphiphilic drug-induced phospholipidosis. However, there is no true validation of this biomarker in human studies, nor a clear identification of the carrier of this endolysosome-specific lipid in biofluids. The present study demonstrates that in absence of any sign of renal failure, BMP, especially all docosahexaenoyl containing species, are significantly increased in the urine of patients treated with the antiarrhythmic drug amiodarone. Such urinary BMP increase could reflect a generalized drug-induced perturbation of the endolysosome compartment as observed in vitro with amiodarone-treated human macrophages. Noteworthy, BMP was associated with extracellular vesicles (EVs) isolated from human urines and extracellular medium of human embryonic kidney HEK293 cells and co-localizing with classical EV protein markers CD63 and ALIX. In the context of drug-induced endolysosomal dysfunction, increased BMP-rich EV release could be useful to remove excess of undigested material. This first human pilot study not only reveals BMP as a urinary biomarker of amiodarone-induced endolysosomal dysfunction, but also highlights its utility to prove the endosomal origin of EVs, also named as exosomes. This peculiar lipid already known as a canonical late endosome-lysosome marker, may be thus considered as a new lipid marker of urinary exosomes.

Microscopic susceptibility anisotropy imaging.

PurposeThe gradient‐echo MR signal in brain white matter depends on the orientation of the fibers with respect to the external magnetic field. To map microstructure‐specific magnetic susceptibility in orientationally heterogeneous material, it is thus imperative to regress out unwanted orientation effects.MethodsThis work introduces a novel framework, referred to as microscopic susceptibility anisotropy imaging, that disentangles the 2 principal effects conflated in gradient‐echo measurements, (a) the susceptibility properties of tissue microenvironments, especially the myelin microstructure, and (b) the axon orientation distribution relative to the magnetic field. Specifically, we utilize information about the orientational tissue structure inferred from diffusion MRI data to factor out the B0‐direction dependence of the frequency difference signal.ResultsA human pilot study at 3 T demonstrates proxy maps of microscopic susceptibility anisotropy unconfounded by fiber crossings and orientation dispersion as well as magnetic field direction. The developed technique requires only a dual‐echo gradient‐echo scan acquired at 1 or 2 head orientations with respect to the magnetic field and a 2‐shell diffusion protocol achievable on standard scanners within practical scan times.ConclusionsThe quantitative recovery of microscopic susceptibility features in the presence of orientational heterogeneity potentially improves the assessment of microstructural tissue integrity.

SMINT

Sharing a pre-trained machine learning model, particularly a deep neural network via prediction APIs, is becoming a common practice on machine learning as a service (MLaaS) platforms nowadays. Although deep neural networks (DNN) have shown remarkable successes in many tasks, they are also criticized for the lack of interpretability and transparency. Interpreting a shared DNN model faces two additional challenges compared with interpreting a general model. (1) Limited training data can be disclosed to users. (2) The internal structure of the models may not be available. These two challenges impede the application of most existing interpretability approaches, such as saliency maps or influence functions, for DNN models. Case-based reasoning methods have been used for interpreting decisions; however, how to select and organize the data points under the constraints of shared DNN models is not discussed. Moreover, simply providing cases as explanations may not be sufficient for supporting instance level interpretability. Meanwhile, existing interpretation methods for DNN models generally lack the means to evaluate the reliability of the interpretation. In this article, we propose a framework named Shared Model INTerpreter (SMINT) to address the above limitations. We propose a new data structure called a boundary graph to organize training points to mimic the predictions of DNN models. We integrate local features, such as saliency maps and interpretable input masks, into the data structure to help users to infer the model decision boundaries. We show that the boundary graph is able to address the reliability issues in many local interpretation methods. We further design an algorithm named hidden-layer aware p-test to measure the reliability of the interpretations. Our experiments show that SMINT is able to achieve above 99% fidelity to corresponding DNN models on both MNIST and ImageNet by sharing only a tiny fraction of training data to make these models interpretable. The human pilot study demonstrates that SMINT provides better interpretability compared with existing methods. Moreover, we demonstrate that SMINT is able to assist model tuning for better performance on different user data.

Multispectral optoacoustic tomography of muscle perfusion and oxygenation under arterial and venous occlusion: A human pilot study.

Perfusion and oxygenation are critical parameters of muscle metabolism in health and disease. They have been both the target of many studies, in particular using near-infrared spectroscopy (NIRS). However, difficulties with quantifying NIRS signals have limited a wide dissemination of the method to the clinics. Our aim was to investigate whether clinical multispectral optoacoustic tomography (MSOT) could enable the label-free imaging of muscle perfusion and oxygenation under clinically relevant challenges: the arterial and venous occlusion. We employed a hybrid clinical MSOT/ultrasound system equipped with a hand-held scanning probe to visualize hemodynamic and oxygenation changes in skeletal muscle under arterial and venous occlusions. Four (N = 4) healthy volunteers were scanned over the forearm for both 3-minute occlusion challenges. MSOT-recorded pathophysiologically expected results during tests of disturbed blood flow with high resolution and without the need for contrast agents. During arterial occlusion, MSOT-extracted Hb-values showed an increase, while HbO2 - and total blood volume (TBV)-values remained roughly steady, followed by a discrete increase during the hyperemic period after cuff deflation. During venous occlusion, results showed a clear increase in intramuscular HbO2 , Hb and TBV within the segmented muscle area. MSOT was found to be capable of label-free non-invasive imaging of muscle hemodynamics and oxygenation under arterial and venous occlusion. We introduce herein MSOT as a novel modality for the assessment of vascular disorders characterized by disturbed blood flow, such as acute limb ischemia and venous thrombosis.

ELECTRICAL MICROCURRENT THERAPY IN PATIENTS WITH CHRONIC HEART FAILURE: A SUCCESSFUL DISRUPTIVE TREATMENT APPROACH

Constant electrical microcurrent (EM) applied to the myocardial tissue effects multiple components of the cardiomyocytes, the extracellular matrix and the intracellular signal transduction. After a series of preclinical trials, we investigated in a human pilot study whether the application of EM

PET imaging urothelial bladder cancer: A novel approach.

443 Background: Urothelial bladder cancer (UBC) inflicts >80,000 new patients annually. Since treatment is stage-dependent, accurate staging is crucial. Conventional imaging and biopsy are often unreliable. A large number of PET tracers, developed to improve imaging, have limitations e.g. urinary excretion compromising their ability to assess the bladder lumen and invasive tumors. This study is to validate a hypothesis that high density VPAC receptors expression on UBC cell surface, can be targeted to PET image UBC, to determine loco-regional disease and metastatic lesions. Methods: Cu-64-TP3805 (4±10% mCi), with its high affinity (3.1 x 10−9M) for VPAC, was given IV to 19 UBC patients (44-80 yrs), scheduled for radical cystectomy. Those eligible for neoadjuvant chemotherapy were treated as such. Urine and blood samples were collected on the day of scan. Whole body PET/CT images acquired 60 to 90 min later and read by two physicians. Surgery was performed 1 to 4 weeks later. Imaging results were correlated with histology. Results: There were no adverse events. Urinary excretion of Cu-64-TP3805 was negligible. Blood clearance was biphasic (t ½ a = 22.3 ±2.7 min ~ 85% and t ½ β = 118.2 ± 4.9 min ~ 15%). VPAC PET bladder images were true positive (TP) in 11, true negative (TN) in 4, false positive (FP) in 1 and false negative (FN) in 3 patients with 79% sensitivity (95% CI 49%-95%), 80% specificity (95% CI 28%-100%), 92% PPV (95% CI 62%-100%), and 57% NPV (95% CI 18%-90%). Prostate images were TP in 8, TN in 6, and FP in 5 patients, with 100% sensitivity (95% CI 63%-100%), 55% specificity (95% CI 23%-83%), 62% PPV (95% CI 32%-86%), and 100% NPV (95% CI 54%-100%). The 5 FP images revealed HGPIN on re-analysis. For lymph nodes, images were TP in 1, TN in 14 and FN in 4 patients, with 25% sensitivity (95% CI 1%-81%), 100% specificity (95% CI 78%-100%), 100% PPV (95% CI 3%-100%), and 83% NPV (95% CI 59%-96%). In one patient, several lesions were seen in the spine and iliac crest. Biopsy was positive for metastasis. In smokers (N=12) there was diffused or focal tracer uptake in the lungs. In 7 non-smokers, 3 with CT depicted abnormality had tracer lung uptake and 4 did not. Conclusions: These first in human pilot study data depict Cu-64-TP3805 VPAC targeting to image UBC as worthy of further investigation.

A Pilot Microbiota Study in Parkinson's Disease Patients versus Control Subjects, and Effects of FTY720 and FTY720-Mitoxy Therapies in Parkinsonian and Multiple System Atrophy Mouse Models.

Background:Parkinson’s disease (PD) and multiple system atrophy (MSA) patients often suffer from gastrointestinal (GI) dysfunction and GI dysbiosis (microbial imbalance). GI dysfunction also occurs in mouse models of PD and MSA.Objectives:To assess gut dysfunction and dysbiosis in PD subjects as compared to controls, identify potential shared microbial taxa in humans and mouse models of PD and MSA, and to assess the effects of potential therapies on mouse GI microbiota.Methods:In this human pilot study, GI function was assessed by fecal consistency/frequency measured using the Bristol Stool Form Scale and GI transit time assessed using Sitzmarks pills and abdominal radiology. Human and mouse microbiota were analyzed by extracting fecal genomic DNA followed by 16S rRNA sequencing.Results:In our PD patients genera Akkermansia significantly increased while a trend toward increased Bifidobacterium and decreased Prevotella was observed. Families Bacteroidaceae and Lachnospiraceae and genera Prevotella and Bacteroides were detected in both humans and PD mice, suggesting potential shared biomarkers. In mice treated with the approved multiple sclerosis drug, FTY720, or with our FTY720-Mitoxy-derivative, we saw that FTY720 had little effect while FTY720-Mitoxy increased beneficial Ruminococcus and decreased Rickenellaceae family.Conclusion:Akkermansia and Prevotellaceae data reported by others were replicated in our human pilot study suggesting the use of those taxa as potential biomarkers for PD diagnosis. The effect of FTY720-Mitoxy on taxa Rikenellaceae and Ruminococcus and the relevance of S24-7 await further evaluation. It also remains to be determined if mouse microbiota have predictive power for human subjects.

A Preliminary Study for Effect of High Flow Oxygen through Nasal Cannula Therapy in Carbon Monoxide Poisoning

Purpose: Acute carbon monoxide (CO) poisoning is one of the most common types of poisoning and a major health problem worldwide. Treatment options are limited to normobaric oxygen therapy, administered using a non-rebreather face mask or hyperbaric oxygen. Compared to conventional oxygen therapy, high-flow nasal cannula oxygen (HFNC) creates a positive pressure effect through high-flow rates. The purpose of this human pilot study is to determine the effects of HFNC on the rate of CO clearance from the blood, in patients with mild to moderate CO poisoning. Methods: CO-poisoned patients were administered 100% oxygen from HFNC (flow of 60 L/min). The fraction of COHb (fCOHb) was measured at 30-min intervals until it decreased to under 10%, and the half-life time of fCOHb (fCOHb t1/2) was subsequently determined. Results: At the time of ED arrival, a total of 10 patients had fCOHb levels ≥10%, with 4 patients ranging between 10% and 50%. The mean rate of fCOHb elimination patterns exhibits logarithmic growth curves that initially increase quickly with time (HFNC equation, Y=0.3388*X+11.67). The mean fCOHbt1/2 in the HFNC group was determined to be 48.5±12.4 minutes. Conclusion: In patients with mild to moderate CO poisoning, oxygen delivered via high flow nasal cannula is a safe and comfortable method to treat acute CO toxicity, and is effective in reducing the COHb half-life. Our results indicate HFNC to be a promising alternative method of delivering oxygen for CO toxicity. Validating the effectiveness of this method will require larger studies with clinical outcomes.

Comparison of high-flow nasal cannula oxygen therapy and conventional reserve-bag oxygen therapy in carbon monoxide intoxication: A pilot study

BackgroundHigh-flow nasal cannula oxygen (HFNC) creates a positive pressure effect through high-flow rates compared to conventional oxygen therapy. The purpose of this human pilot study is to compare the effects of HFNC and conventional oxygen therapy on the rate of carbon monoxide (CO) clearance from the blood in patients with mild to moderate CO poisoning. MethodsCO-poisoned Patients randomly received 100% oxygen from a rebreathing reserve mask (NBO2, flow of 15 L/min) or HFNC (flow of 60 L/min). The fraction of COHb value (fCOHb) was measured in 30-min intervals until it fell to under 10%. We determined the Half-life time of fCOHb (fCOHb t1/2). ResultsA total of 22 patients had fCOHb levels ≥ 10% at the time of ED arrival, with 9 of them having fCOHb level ranging between 25% and 50%. There was no significant difference in the fCOHbt1/2 between the HFNC group and NBO2 group. However, the mean fCOHbt1/2 in the HFNC group (48.5 ± 12.4 min) has a smaller standard deviation than that in the NBO2 group (99.3 ± 93.38 min). There were significant between-group differences in the mean COHbt1/2 among the patients with fCOHb levels less than 25% (HFNC 43.6 ± 10.6 vs. NBO2 134.2 ± 111.3). ConclusionsIn this pilot randomized controlled trial study, HFNC therapy did not reduce fCOHbt1/2 compared to NBO2 therapy but could be beneficial in maintaining a constant fCOHbt1/2 as well as in reducing fCOHbt1/2 in mild CO poisoning patients compared to conventional NBO2 therapy. However, further studies with a larger number of patients are needed to establish HFNC therapy as an alternative therapy for CO poisoning patients.

1881PD - Oral intestinal alkaline phosphatase improves efficacy of 5-FU in a colorectal cancer mouse model

BackgroundIntestinal alkaline phosphatase (IAP) is an endogenous intestinal enzyme that promotes gastrointestinal (GI) homeostasis by detoxifying inflammatory mediators, tightening the gut barrier and promoting a healthy microbiome. In previous reports, oral delivery of IAP ameliorated colitis in animals and in a human pilot study. The commonly used chemotherapy, 5-Fluorouracil (5-FU), can cause severe GI damage potentially resulting in dose limiting toxicities. Given the recent implication of the gut microbiome in modulating the anti-cancer response and the role of IAP in mitigating GI toxicity, we sought to evaluate the role of IAP in ameliorating 5-FU related GI side effects and to assess the impact of IAP therapy on anti-cancer efficacy. MethodsBALB/c mice were inoculated with CT26 murine colorectal cancer cells into the right flank. 5-FU (30mg/kg) was given IP QD for 5 consecutive days. IAP (0.5mg/kg) or vehicle was administered PO BID throughout the study. Mice were evaluated for stool consistency, tumor growth and survival. A cohort of mice was sacrificed at day 5 for histopathology analysis. Results5-FU administration caused loose stools/diarrhea in all the treated animals, which peaked at day 6 and recovered by day 9. Interestingly, mice that received IAP showed a significantly faster recovery (p<0.03). As expected, 5-FU slowed tumor progression compared to controls (no 5-FU). Surprisingly, IAP addition significantly improved anti-cancer efficacy. Mice treated with IAP showed diminished tumor growth compared to vehicle (at day 19, 1066 vs 1968mm3, p<0.05). Furthermore, IAP administration significantly prolonged animal survival when compared to vehicle-treated animals (p<0.02). Mechanistically, 5-FU led to goblet cell loss whereas IAP treatment protected the goblet cells. ConclusionsOral administration of IAP in mice not only improved some of the side effects associated with 5-FU, such as diarrhea and potentially mucositis, but also enhanced the anti-tumor efficacy of 5-FU leading to significantly prolonged survival. Overall, IAP has the potential to become a new therapeutic agent intended to mitigate cancer-treatment side effects and to enhance the overall anti-tumor response. Legal entity responsible for the studyThe authors. FundingSynthetic Biologics. DisclosureC. Furlan Freguia: Full / Part-time employment: Synthetic Biologics. M. Kaleko: Full / Part-time employment: Synthetic Biologics.