Effects of hyperbaric oxygen therapy on exercise-induced muscle damage.

Purpose: To perform a literature review on hyperbaric oxygen (HBO2) therapy as a treatment for exercise-induced muscle damage (EIMD). Methods: PubMed, Web of Science and Google Scholar were searched for articles related to HBO2 therapy as a treatment for exercise-induced muscle damage. Inclusion criteria included HBO2 therapy as the primary intervention to treat EIMD. Articles used in this review ranged from 1995-2021. Conclusion: Current literature on the effectiveness of HBO2 therapy to treat EIMD is mixed. Early and frequent treatments seem to be important factors when it comes to the success of HBO2 therapy. Additional research is needed to determine if HBO2 therapy has potential to treat more severe forms of EIMD and the role HBO2 therapy has on inflammation and satellite cell function after EIMD.

Combination and Comparison of Sound Coding Strategies Using Cochlear Implant Simulation With Mandarin Speech.

Three cochlear implant (CI) sound coding strategies were combined in the same signal processing path and compared for speech intelligibility with vocoded Mandarin sentences. The three CI coding strategies, biologically-inspired hearing aid algorithm (BioAid), envelope enhancement (EE), and fundamental frequency modulation (F0mod), were combined with the advanced combination encoder (ACE) strategy. Hence, four singular coding strategies and four combinational coding strategies were derived. Mandarin sentences with speech-shape noise were processed using these coding strategies. Speech understanding of vocoded Mandarin sentences was evaluated using short-time objective intelligibility (STOI) and subjective sentence recognition tests with normal-hearing listeners. For signal-to-noise ratios at 5 dB or above, the EE strategy had slightly higher average scores in both STOI and listening tests compared to ACE. The addition of EE to BioAid slightly increased the mean scores for BioAid+EE, which was the combination strategy with the highest scores in both objective and subjective speech intelligibility. The benefits of BioAid, F0mod, and the four combinational coding strategies were not observed in CI simulation. The findings of this study may be useful for the future design of coding strategies and related studies with Mandarin.

Hyperbaric oxygen therapy and fluorescence angiography in arterial insufficiency secondary to injection of crushed hydromorphone.

INTRODUCTION: Foreign body emboli can lead to acute arterial insufficiency. We present a case report of upper extremity arterial insufficiency in an intravenous (IV) drug user secondary to intra-arterial injection of crushed tablet particles successfully treated with hyperbaric oxygen (HBO2) therapy. CASE: A 37-year-old right-hand-dominant male developed pain and swelling of the left hand after attempting to inject crushed hydromorphone tablets into his venous circulation. Angiography revealed incomplete distal filling of the proper digital arteries, princeps pollicis, and radialis indicis branches of the left hand. The patient was treated with HBO2 for acute arterial insufficiency, secondary to these findings. Fluorescence angiography was performed prior to, during and after completion of HBO2, which showed improved perfusion of the hand upon completion of serial imaging. The patient underwent subsequent partial amputation of the left second digit and removal of the thenar and third finger pads. DISCUSSION: Much of the literature on treatment of arterial insufficiency with HBO2 are in relation to chronic problem wounds. However, there is limited data on adjunctive treatment with HBO2 for foreign body embolism. Fluorescence angiography and clinical exam were used to track tissue perfusion and progression throughout course of therapy with HBO2. CONCLUSION: Acute arterial insufficiency induced by foreign body embolism was successfully treated with HBO2 and provided increased tissue salvage of the patient's hand. The use of fluorescence angiography as a secondary measure of perfusion can provide additional insight regarding qualitative tissue oxygenation and may be a viable tool to track patient progress during HBO2 treatment.

Performance characteristics of high-frequency percussive ventilation under hyperbaric conditions.

Introduction: Safe administration of critical care hyperbaric medicine requires specialized equipment and advanced training. Equipment must be tested in order to evaluate function in the hyperbaric environment. High-frequency percussive ventilation (HFPV) has been used in intensive care settings effectively, but it has never been tested in a hyperbaric chamber. Methods: Following a modified U.S. Navy testing protocol used to evaluate hyperbaric ventilators, we evaluated an HFPV transport ventilator in a multiplace hyperbaric chamber at 1.0, 1.9, and 2.8 atmospheres absolute (ATA). We used a test lung with analytical software for data collection. The ventilator uses simultaneous cyclic pressure-controlled ventilation at a pulsatile flow rate (PFR)/oscillatory continuous positive airway pressure (oCPAP) ratio of 30/10 with a high-frequency oscillation percussive rate of 500 beats per minute. Inspiratory and expiratory times were maintained at two seconds throughout each breathing cycle. Results: During manned studies, the PFR/oCPAP ratios were 26/6, 22/7, and 22.5/8 at an airway resistance of 20cm H2O/L/second and 18/9, 15.2/8.5, and 13.6/7 at an airway resistance of 50 cm/H2O/L/second at 1, 1.9, and 2.8 ATA. The resulting release volumes were 800, 547, and 513 mL at airway resistance of 20 cm H2O/L/sec and 400, 253, and 180 mL at airway resistance of 50 cm/H2O/L/sec at 1, 1.9, and 2.8 ATA. Unmanned testing showed similar changes. The mean airway pressure (MAP) remained stable throughout all test conditions; theoretically, supporting adequate lung recruitment and gas exchange. A case where HFPV was used to treat a patient for CO poisoning was presented to illustrate that HFPV worked well under HBO2 conditions and no complications occurred during HBO2 treatment. Conclusion: The HFPV transport ventilator performed adequately under hyperbaric conditions and should be considered a viable option for hyperbaric critical care. This ventilator has atypical terminology and produces unique pulmonary physiology, thus requiring specialized training prior to use.

Physiologic and biochemical rationale for treating COVID-19 patients with hyperbaric oxygen.

The SARS-Cov-2 (COVID-19) pandemic remains a major worldwide public health issue. Initially, improved supportive and anti-inflammatory intervention, often employing known drugs or technologies, provided measurable improvement in management. We have recently seen advances in specific therapeutic interventions and in vaccines. Nevertheless, it will be months before most of the world's population can be vaccinated to achieve herd immunity. In the interim, hyperbaric oxygen (HBO2) treatment offers several potentially beneficial therapeutic effects. Three small published series, one with a propensity-score-matched control group, have demonstrated safety and initial efficacy. Additional anecdotal reports are consistent with these publications. HBO2 delivers oxygen in extreme conditions of hypoxemia and tissue hypoxia, even in the presence of lung pathology. It provides anti-inflammatory and anti-proinflammatory effects likely to ameliorate the overexuberant immune response common to COVID-19. Unlike steroids, it exerts these effects without immune suppression. One study suggests HBO2 may reduce the hypercoagulability seen in COVID patients. Also, hyperbaric oxygen offers a likely successful intervention to address the oxygen debt expected to arise from a prolonged period of hypoxemia and tissue hypoxia. To date, 11 studies designed to investigate the impact of HBO2 on patients infected with SARS-Cov-2 have been posted on clinicaltrials.gov. This paper describes the promising physiologic and biochemical effects of hyperbaric oxygen in COVID-19 and potentially in other disorders with similar pathologic mechanisms.

ARTERIAL INSUFFICIENCIES: Hyperbaric Oxygen Therapy for Selected Problem Wounds.

The use of hyperbaric oxygen (HBO2) for the treatment of selected problem wounds has focused almost entirely on the diabetic foot ulcer (DFU) in recent years. The prevalence of DFUs in today's patient population and the reimbursement available for the treatment of DFUs have given it priority status in discussions about problem wounds, but there are sound fundamental reasons why additional oxygen may have benefits in the treatment of non-DFU wounds.

Safety of a continuous glucose monitoring device during hyperbaric exposure.

Background: Hyperbaric oxygen therapy has been demonstrated to lower blood glucose levels in patients with diabetes. Continuous glucose monitoring (CGM) allows glucose monitoring in real time. Battery-operated CGM transmitters have yet to be formally tested and given safety approval for use in a hyperbaric environment. Materials and Methods: We evaluated and tested commercially available Dexcom® G6 CGM transmitters under hyperbaric conditions. Each transmitter contains a 3V, 130-mAh (0.39 Wh) lithium manganese dioxide battery (IEC CR1632) and circuit board that are fully encapsulated in epoxy. Each transmitter is pressurized to 90 pounds per square inch (psi) in an autoclave at 40°C for up to 72 hours during manufacturing to ensure that all enclosed air spaces are eliminated from the epoxy. We compared the CGM components against section 14.2.9.3.17.5 of the 2018 National Fire Protection Association 99 (NFPA 99) Health Care Facilities Code requirements. Six CGM transmitters attached to estimated glucose value generators (EGVGs) underwent 11 pressurization cycles to 45 feet of seawater (fsw). All transmitters were returned to the manufacturer to assess post-exposure structural integrity. G6 sensors, which contain no electrical components or compressible air spaces, do not pose a risk in the hyperbaric environment. Results: There was no observed change in preset EGVG readings during hyperbaric exposures. Post-exposure testing revealed no structural compromise after repeated hyperbaric exposures. Conclusions: The CGM transmitter meets section 14.2.9.3.17.5 of the 2018 NFPA 99 requirements for battery-operated devices allowed for use in a hyperbaric environment. This analysis revealed no significant safety concerns with subjecting Dexcom G6 CGM transmitters to hyperbaric environments.

Reliability of the Dexcom G6 Continuous Glucose Monitor During Hyperbaric Oxygen Exposure.

Background: People with diabetes-related ulcers may benefit from hyperbaric oxygen (HBO2) therapy and from continuous glucose monitors (CGM). Although blood glucose (BG) meters based on glucose oxidase (GO) report erroneously low values at high pO2, BG meters based on glucose dehydrogenase (GD) do not. We therefore examined the performance of a GO-based CGM system in comparison to GO-based and GD-based BG systems in normobaric air (NBAir), hyperbaric air (HBAir), and HBO2 environments. Materials and Methods: Twenty-six volunteers without diabetes mellitus (DM) wore Dexcom G6 CGM systems and provided periodic blood samples before, during, and after a standard HBO2 treatment consisting of three 30-min intervals of HBO2 separated by two 5-min intervals of HBAir. Accuracy of the CGM and GO-based BG meter were assessed by comparisons with the GD-based values. Results: The mean absolute relative difference for the CGM system was 15.96% and for the GO-based meter was 8.52%. Compared to NBAir, HBO2 exposure resulted in significantly higher CGM values (+3.76 mg/dL, P < 0.001) and significantly lower GO-based meter values (-10.38 mg/dL, P < 0.001). Pre-HBO2 and post-HBO2 values obtained in NBAir were also significantly different when measured by CGM (+4.13 mg/dL, P = 0.015) or the GO-based meter (-9.04 mg/dL, P < 0.001). Conclusions: In volunteers without DM, HBO2 exposure results in statistically significant differences in glucose measurements obtained with GO-based devices, but not a GD-based device. Standard HBO2 treatment results in statistically significant effects on glucose concentrations. These differences are of unlikely clinical significance.

Impact of Hyperbaric Oxygen on More Advanced Wagner Grades 3 and 4 Diabetic Foot Ulcers: Matching Therapy to Specific Wound Conditions.

Objective: The goal of this research was to identify a population of diabetic foot ulcer patients who demonstrate a significant response to hyperbaric oxygen therapy (HBOT) using a large sample size to provide guidance for clinicians when treating these complicated patients. Approach: The effect of HBOT on diabetic foot ulcers, Wagner grades 3 and 4, was evaluated using a retrospective observational real-world data set. The study reported on the overall healing rate, (74.2%) at the population level, for >2 million wounds. Results: When a subgroup of patients of only foot ulcers with a Wagner grade 3 or 4 were considered, the healing rate was only 56.04%. The use of HBOT, without filtering for the number of treatments received, improved the healing rate to 60.01% overall. Healing rates for this same subgroup, however, were improved to 75.24% for patients who completed the prescribed number of hyperbaric treatments. Innovation: This observational study discusses the importance of reporting at the population level, specific wound etiology level, a risk-stratified level, and to then overlay the effect of treatment adherence on those outcomes to provide clinicians with a comprehensive understanding of when to prescribe an advanced modality such as hyperbaric oxygen. Conclusion: The authors provide healing outcomes data from several prior HBOT studies as well as other advanced modalities that have been used in diabetic foot ulcer care for comparison and context.

A clinical practice guideline for the use of hyperbaric oxygen therapy in the treatment of diabetic foot ulcers.

BACKGROUND: The role of hyperbaric oxygen (HBO2) for the treatment of diabetic foot ulcers (DFUs) has been examined in the medical literature for decades. There are more systematic reviews of the HBO2/DFU literature than there have been randomized controlled trials (RCTs), but none of these reviews has resulted in a clinical practice guideline (CPG) that clinicians, patients and policy-makers can use to guide decision-making in everyday practice. METHODS: The Undersea and Hyperbaric Medical Society (UHMS), following the methodology of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group, undertook this systematic review of the HBO2 literature in order to rate the quality of evidence and generate practice recommendations for the treatment of DFUs. We selected four clinical questions for review regarding the role of HBO2 in the treatment of DFUs and analyzed the literature using patient populations based on Wagner wound classification and age of the wound (i.e., acute post-operative wound vs. non-healing wound of 30 or more days). Major amputation and incomplete healing were selected as critical outcomes of interest. RESULTS: This analysis showed that HBO2 is beneficial in preventing amputation and promoting complete healing in patients with Wagner Grade 3 or greater DFUs who have just undergone surgical debridement of the foot as well as in patients with Wagner Grade 3 or greater DFUs that have shown no significant improvement after 30 or more days of treatment. In patients with Wagner Grade 2 or lower DFUs, there was inadequate evidence to justify the use of HBO2 as an adjunctive treatment. CONCLUSIONS: Clinicians, patients, and policy-makers should engage in shared decision-making and consider HBO2 as an adjunctive treatment of DFUs that fit the criteria outlined in this guideline. The current body of evidence provides a moderate level of evidence supporting the use of HBO2 for DFUs. Future research should be directed at improving methods for patient selection, testing various treatment protocols and improving our confidence in the existing estimates.

Causal reasoning on biological networks: interpreting transcriptional changes.

MOTIVATION: The interpretation of high-throughput datasets has remained one of the central challenges of computational biology over the past decade. Furthermore, as the amount of biological knowledge increases, it becomes more and more difficult to integrate this large body of knowledge in a meaningful manner. In this article, we propose a particular solution to both of these challenges. METHODS: We integrate available biological knowledge by constructing a network of molecular interactions of a specific kind: causal interactions. The resulting causal graph can be queried to suggest molecular hypotheses that explain the variations observed in a high-throughput gene expression experiment. We show that a simple scoring function can discriminate between a large number of competing molecular hypotheses about the upstream cause of the changes observed in a gene expression profile. We then develop an analytical method for computing the statistical significance of each score. This analytical method also helps assess the effects of random or adversarial noise on the predictive power of our model. RESULTS: Our results show that the causal graph we constructed from known biological literature is extremely robust to random noise and to missing or spurious information. We demonstrate the power of our causal reasoning model on two specific examples, one from a cancer dataset and the other from a cardiac hypertrophy experiment. We conclude that causal reasoning models provide a valuable addition to the biologist's toolkit for the interpretation of gene expression data. AVAILABILITY AND IMPLEMENTATION: R source code for the method is available upon request.

Empowering industrial research with shared biomedical vocabularies.

The life science industries (including pharmaceuticals, agrochemicals and consumer goods) are exploring new business models for research and development that focus on external partnerships. In parallel, there is a desire to make better use of data obtained from sources such as human clinical samples to inform and support early research programmes. Success in both areas depends upon the successful integration of heterogeneous data from multiple providers and scientific domains, something that is already a major challenge within the industry. This issue is exacerbated by the absence of agreed standards that unambiguously identify the entities, processes and observations within experimental results. In this article we highlight the risks to future productivity that are associated with incomplete biological and chemical vocabularies and suggest a new model to address this long-standing issue.

Structure-based druggability assessment--identifying suitable targets for small molecule therapeutics.

A target is druggable if it can be modulated in vivo by a drug-like molecule. The general properties of oral drugs are summarized by the 'rule of 5' which specifies parameters related to size and lipophilicity. Structure-based target druggability assessment consists of predicting ligand-binding sites on the protein that are complementary to these drug-like properties. Automated identification of ligand-binding sites can use geometrical considerations alone or include specific physicochemical properties of the protein surface. Features of a pocket's size and shape, together with measures of its hydrophobicity, are most informative in identifying suitable drug-binding pockets. The recent availability of several validation sets of druggable versus undruggable targets has helped fuel the development of more elaborate methods.

Physiochemical drug properties associated with in vivo toxicological outcomes.

Relationships between physicochemical drug properties and toxicity were inferred from a data set consisting of animal in vivo toleration (IVT) studies on 245 preclinical Pfizer compounds; an increased likelihood of toxic events was found for less polar, more lipophilic compounds. This trend held across a wide range of types of toxicity and across a broad swath of chemical space.

Beyond data integration.

Pharmaceutical R&D organizations have no shortage of experimental data or annotation information. However, the sheer volume and complexity of this information results in a paralyzing inability to make effective use of it for predicting drug efficacy and safety. Data integration efforts are legion, but even in the rare instances where they succeed, they are found to be insufficient to advance programs because interpretation of query results becomes a research project in itself. In this review, we propose a coherent, interoperable platform comprising knowledge engineering and hypothesis generation components for rapidly making determinations of confidence in mechanism and safety (among other goals) using experimental data and expert knowledge.