Persufflation—Current State of Play

With the ever-increasing disparity between the number of patients waiting for organ transplants and the number organs available, some patients are unable to receive life-saving transplantation in time. The present, widely-used form of preservation is proving to be incapable of maintaining organ quality during long periods of preservation and meeting the needs of an ever-changing legislative and transplantation landscape. This has led to the need for improved preservation techniques. One such technique that has been extensively researched is gaseous oxygen perfusion or Persufflation (PSF). This method discovered in the early 20th century has shown promise in providing both longer term preservation and organ reconditioning capabilities for multiple organs including the liver, kidneys, and pancreas. PSF utilises the organs own vascular network to provide oxygen to the organ tissue and maintain metabolism during preservation to avoid hypoxic damage. This review delves into the history of this technique, its multiple different approaches and uses, as well as in-depth discussion of work published in the past 15 years. Finally, we discuss exciting commercial developments which may help unlock the potential for this technique to be applied at scale.

A new principle for the diagnosis morphea in the onset of the disease

BACKGROUND: Because of the low specificity morphea clinical manifestations in early stages, the differential diagnosis is difficult. AIMS: The purpose of the research is to propose a new diagnostic method for early stages of localized scleroderma. MATERIALS AND METHODS: During 20112020, 77 patients with clinical manifestations of morphea and 127 controls were examined and included in the study at the LenOblCenter. All participants were conducted a transcutaneous oximetry with the TCM-400 Radiometer apparatus. The tissue oxygen perfusion (tcpO2) level from 40 to 50 mm Hg was considered as a reversible decrease, from 30 to 40 mm hg was a borderline decline and the value below 30 mm hg was critical. The following diagnostic skin biopsy was conducted in all 77 patients RESULTS: Skin biopsy allowed to form 4 research groups: 40 patients with morphea, 12 patients with granuloma annulare, 15 patients with small plaque parapsoriasis and 10 individuals with large plaque parapsoriasis. 7 (17.5%) patients with morphea had normal tcpO2 values, 9 (22.5%) patients had significant decrease of tcpO2, 24 patients (60%) showed a reversible decrease of tcpO2. 3/12 (25%) patients with granuloma annulare and 1 patient (10%) with large plaque parapsoriasis had minor oxygen level decrease. Measurement on the healthy skin showed tcpO2 decrease in patients with comorbidities ― 3/77 (3.9%) in research group and 28/127 (22%) in controls. CONCLUSIONS: Transcutaneous oximetry is a new perspective direction in the diagnostic algorithm of the morphea based on the pathogenesis and morphological features of the disease.

Morphometric Analysis of Brain in Newborn with Congenital Diaphragmatic Hernia

Congenital diaphragmatic hernia (CDH) is a severe pediatric disorder with herniation of abdominal viscera into the thoracic cavity. Since neurodevelopmental impairment constitutes a common outcome, we performed morphometric magnetic resonance imaging (MRI) analysis on CDH infants to investigate cortical parameters such as cortical thickness (CT) and local gyrification index (LGI). By assessing CT and LGI distributions and their correlations with variables which might have an impact on oxygen delivery (total lung volume, TLV), we aimed to detect how altered perfusion affects cortical development in CDH. A group of CDH patients received both prenatal (i.e., fetal stage) and postnatal MRI. From postnatal high-resolution T2-weighted images, mean CT and LGI distributions of 16 CDH were computed and statistically compared to those of 13 controls. Moreover, TLV measures obtained from fetal MRI were further correlated to LGI. Compared to controls, CDH infants exhibited areas of hypogiria within bilateral fronto-temporo-parietal labels, while no differences were found for CT. LGI significantly correlated with TLV within bilateral temporal lobes and left frontal lobe, involving language- and auditory-related brain areas. Although the causes of neurodevelopmental impairment in CDH are still unclear, our results may suggest their link with altered cortical maturation and possible impaired oxygen perfusion.

Voxelized simulation of cerebral oxygen perfusion elucidates hypoxia in aged mouse cortex

Departures of normal blood flow and metabolite distribution from the cerebral microvasculature into neuronal tissue have been implicated with age-related neurodegeneration. Mathematical models informed by spatially and temporally distributed neuroimage data are becoming instrumental for reconstructing a coherent picture of normal and pathological oxygen delivery throughout the brain. Unfortunately, current mathematical models of cerebral blood flow and oxygen exchange become excessively large in size. They further suffer from boundary effects due to incomplete or physiologically inaccurate computational domains, numerical instabilities due to enormous length scale differences, and convergence problems associated with condition number deterioration at fine mesh resolutions. Our proposed simple finite volume discretization scheme for blood and oxygen microperfusion simulations does not require expensive mesh generation leading to the critical benefit that it drastically reduces matrix size and bandwidth of the coupled oxygen transfer problem. The compact problem formulation yields rapid and stable convergence. Moreover, boundary effects can effectively be suppressed by generating very large replica of the cortical microcirculation in silico using an image-based cerebrovascular network synthesis algorithm, so that boundaries of the perfusion simulations are far removed from the regions of interest. Massive simulations over sizeable portions of the cortex with feature resolution down to the micron scale become tractable with even modest computer resources. The feasibility and accuracy of the novel method is demonstrated and validated with in vivo oxygen perfusion data in cohorts of young and aged mice. Our oxygen exchange simulations quantify steep gradients near penetrating blood vessels and point towards pathological changes that might cause neurodegeneration in aged brains. This research aims to explain mechanistic interactions between anatomical structures and how they might change in diseases or with age. Rigorous quantification of age-related changes is of significant interest because it might aide in the search for imaging biomarkers for dementia and Alzheimer’s disease.

Effective Tumor Vessel Barrier Disruption Mediated by Perfluoro-N-(4-methylcyclohexyl) Piperidine Nanoparticles to Enhance the Efficacy of Photodynamic Therapy

Currently, limited tumor drug permeation, poor oxygen perfusion and immunosuppression microenvironment are the most important bottlenecks that significantly reduce the efficacy of photodynamic therapy (PDT). The main cause of these...

Do Pre-Operative Transcutaneous Oxygen Perfusion Measurements Predict Atraumatic Major Lower Extremity Amputation Wound Healing?

Category: Other Introduction/Purpose: Determining appropriate amputation level is a challenging task requiring clinical, laboratory, and imaging data. However, there is no validated consensus on the method with the most prognostic accuracy. Transcutaneous oxygen perfusion measurement (TcPO2) is a noninvasive means of measuring tissue oxygenation. A TcPO2 > 30-40mm Hg is widely cited as a positive predictor of post-operative wound healing, but its validity has not been well defined. We hypothesized that TcPO2 levels positively correlate with the success of amputation wound healing. Additionally, we secondarily investigated the correlation between other preoperative demographics and clinical variables and their impact on post-operative amputation wound healing. Methods: A retrospective chart review was performed on patients who underwent lower extremity above, through, or below knee amputations at a single institution with documented preoperative TcPO2 values between January 1, 2012 and December 1, 2018 and a minimum 30 days post-operative clinical follow up. Amputations performed for oncologic pathology, infected arthroplasty, osteomyelitis and traumatic amputations were excluded in order to isolate TcPO2 as a decision-making test for amputation level. This yielded one hundred and forty-one total amputations. Of these ninety-three were below knee amputations (BKA), six through knee amputations, and forty-two above knee amputations (AKA). Chi-square and t-tests were used to compare successful and failed amputations where appropriate. Results: Eighty-six of the amputations were successful and fifty-five failed, as defined by post-operative wound dehiscence or infection. Of these, thirty-seven were BKAs, four were through knee amputations and fourteen were AKAs. There was a significant difference in preoperative TcPO2 levels between the successful and failure groups at 46.2 and 38.3 respectively (p = 0.02). A TcPO2 of 30-40mm Hg had a success rate of 68.8%, and a TcPO2 < 20mm Hg a success rate of 18.2%. A receiver operating characteristic curve for TcPO2 levels predicting amputation success elucidated that with an area under the curve of 0.53 for the AKA cohort and 0.61 for the BKA cohort, the diagnostic ability is far from prognostic. Conclusion: Our results provide new insight into the predictive accuracy of preoperative TcPO2 levels. There is not a linear association between TcPO2 and success rate. A TcPO2 < 20mm Hg has a high positive predictive value for failure, but higher TcPO2 levels are not 100% predictive of amputation wound healing as reported by prior studies. Multiple factors should be considered when selecting amputation level.

PENGARUH PEMBERIAN OKSIGEN DAN ELEVASI KEPALA 30º TERHADAP TINGKAT KESADARAN PADA PASIEN CEDERA KEPALA SEDANG

Head injury is directly or indirectly mechanical injuries that resulted wound in the scalp, skull fracture, tear the lining of the brain, and brain damage, and neurological disorders. The basic method for brain protection of head injury patients are freeing the airway and giving adequate oxygenation. Giving oxygen and headv elevation 30° of head are the appropriate action for the moderate head injury classification to launch the cerebral oxygen perfusion and to increase consciousness level. The purpose of this research were to determine the GCS before and after giving oxygenation with and position 30 ° of head and to analyze the effect of giving oxygen and headv elevation30 °of head to change the levels of consciousness of moderate head injury patients. This research was an Quasi-Experimental study with 10 respondents. The test were used Paired Sample T-test Test. The results showed that there was an effect of giving oxygen and headv elevation 30 °of head toward to change the level of consciousness of moderate head injury patients. GCS average value before was 10.10 and GCS average after 12.90 value was with p value was 0.000. Keywords : Levels of Consciousness GCS, Moderate Head Injury, Position 30° of the Head

Overcoming hypoxia-induced functional suppression of NK cells

BackgroundNatural killer (NK) cells are immune cells capable of killing virally infected cells and tumor cells without the need for antigen stimulation. Tumors, however, can create a suppressive microenvironment that decreases NK function. A feature of many tumors is hypoxia (low oxygen perfusion), which has been previously shown to decrease NK function. A high affinity NK (haNK) cell has been engineered to express a high affinity CD16 receptor as well as internal interleukin (IL)-2 for increased antibody-dependent cellular cytotoxicity (ADCC) and activation, respectively. We sought to investigate the tolerance of NK cells versus haNK cells to hypoxia.MethodsWe exposed healthy donor (HD) NK and X-irradiated haNK cells to normoxia (20% oxygen) as well as hypoxia (0% oxygen) and investigated their ability to kill prostate, breast and lung tumor cell lines after 5 hours. We also used monoclonal antibodies cetuximab (anti-EGFR) or avelumab (antiprogrammed death-ligand 1) to investigate the effects of hypoxia on NK ADCC. Genomic and proteomic analyzes were done to determine the effect of hypoxia on the expression of factors important to NK cell function.ResultsWhile HD NK cell cytolytic abilities were markedly and significantly impaired under hypoxic conditions, haNK cells maintained killing capacity under hypoxic conditions. NK killing, serial killing and ADCC were maintained under hypoxia in haNK cells. IL-2 has been previously implicated in serial killing and perforin regeneration and thus the endogenous IL-2 produced by haNK cells is likely a driver of the maintained killing capacity of haNK cells under hypoxic conditions. Activation of signal transducer and activator of transcription 3 (STAT3) is not seen in haNKs under hypoxia but is significant in HD NK cells. Pharmaceutical activation of STAT3 in haNKs led to reduced killing, implicating active STAT3 in reduced NK cell function.ConclusionsIn contrast to HD NK cells, haNK cells are resistant to acute hypoxia. The potent cytolytic function of haNK cells was maintained in an environment comparable to what would be encountered in a tumor. The data presented here provide an additional mechanism of action for haNK cells that are currently being evaluated in clinical trials for several tumor types.

Animal models of necrotizing enterocolitis

BackgroundNecrotizing enterocolitis (NEC) is one of the leading causes of death in premature infants. To determine the factors present in the disease that lead to increased morbidity and mortality, manipulation of variables that are shown to have a positive response has been tested using various animal models. Testing and manipulation of these variables are unwarranted in humans due to regulatory health standards.MethodsThe purpose of this review is to provide an update to previous summaries that determine the significance of animal models in studying the mechanisms of NEC. A large variety of animal models including rats, mice, rabbits, piglets, nonhuman primates, and quails have been described in literature. We reviewed the reported animal models of NEC and examined the pros and cons of the various models as well as the scientific question addressed.ResultsThe animals used in these experiments were subject to gavage feeding, hypoxia, hypothermia, oxygen perfusion, and other methods to induce the disease state. Each of these models has been utilized to show the effects of NEC on the premature, undeveloped gut in animals to find a correlation to the disease state present in humans. We found specific advantages and disadvantages for each model.ConclusionsRecent advances in our understanding of NEC and the ongoing therapeutic strategy developments underscore the importance of animal models for this disease.