Extracorporeal membrane oxygenation for COVID-19: An evolving experience through multiple waves.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has shown variable results in COVID-19 pneumonia however, some evidence supports benefit. Here we compare our institution's ECMO outcomes across multiple waves of the COVID-19 pandemic. METHODS: All patients who received ECMO for COVID-19 between March 1, 2020, and March 1, 2021, were reviewed. Patients received venovenous (VV) or right ventricular assist device (RVAD/ECMO) ECMO. Early (March 1-July 6, 2020, Era 1) and late (July 7, 2020-March 1, 2021, Era 2) pandemic RVAD/ECMO patients were compared. RESULTS: Fifty-four patients received ECMO of which 16 (29.6%) patients received VV ECMO and 38 (70.4%) RVAD/ECMO. Median age was 53.0 years, body mass index 36.1 kg/m2 , 41.2% female, and 49% Caucasian. The most common pre-cannulation treatments included steroids (79.6%) and convalescent plasma (70.4%). Median time from admission to cannulation was 7.0 days. Median support time was 30.5 days (VV ECMO 35.0 days, RVAD/ECMO 26.0 days). In- hospital mortality was 42.6% (39.5% RVAD/ECMO, 50.0% VV ECMO). Significant morbidities included infection (80.8%), bleeding events (74.5%), and renal replacement therapy (30.8%). Cumulative mortality 120-days post-cannulation was 45.7% (VV ECMO 60.8%, RVAD/ECMO 40.0%). RVAD/ECMO Era 1 demonstrated a significantly lower cumulative mortality (16.2%) compared to Era 2 (60.4%). Competing risk analysis found age (HR 0.95, [95% CI 0.92, 0.98] p = 0.005) to be a protective factor for survival. CONCLUSION: ECMO support for COVID-19 is beneficial but carries significant morbidity. RVAD/ECMO support demonstrated consistent advantages in survival to VV-ECMO, but with declining efficacy across time during the COVID-19 pandemic.

Acute cardiopulmonary failure in a young woman with high-risk gestational trophoblastic neoplasia: A case of induction chemotherapy during extracorporeal membrane oxygenation.

•Early use of extracorporeal membrane oxygenation (ECMO) is valuable when pulmonary tumor burden from GTN is high.•Induction chemotherapy of cisplatin and etoposide was administered during ECMO successfully.•The induction chemotherapy regimen led to exponential decline in beta-HCG after 1 cycle.•Collaboration of subspecialists is necessary to treat coexisting malignancy and cardiopulmonary failure associated with GTN.

Experimental and theoretical analyses of the age-dependent large-strain behavior of Sylgard 184 (10:1) silicone elastomer.

The commercial polydimethysiloxane elastomer Sylgard(®) 184 with mixing ratio 10:1 is in wide use for biomedical research or fundamental studies of mechanobiology. In this paper, a comprehensive study of the large strain mechanical behavior of this material under multiaxial monotonic and cyclic loads, and its change during the first 26 days after preparation is reported. The equibiaxial stress response studied in inflation experiments reveals a much stiffer and more nonlinear response compared to the uniaxial and pure shear characteristics. The polymer revealed remarkably elastic behavior, in particular, very little dependence on strain rates between 0.3%/s and 11%/s, and on the strain history in cyclic experiments. On the other hand, both the small-strain and large strain nonlinear mechanical characteristics of the elastomer are changing with sample age and the results suggest that this process has not ceased after 26 days. A recent re-interpretation of the well-known Ogden model for incompressible rubber-like materials was applied to rationalize the results and accurate agreement was obtained with the experimental data over all testing configurations and testing times. The change of a single parameter in this model is shown to govern the evolution of the nonlinear material characteristics with sample age, attributed to a continuation of the cross-linking process. Based on a kinetic relation to account for this process over time, the model provided successful predictions of the material behavior even after more than one year.

Arterial flow waveforms, vascular tone, and chronic fatigue: a case report.

We present the case of a patient with chronic fatigue secondary to Postural Orthostatic Tachycardia Syndrome (POTS) who had distinctive abnormalities in his arterial waveform morphology as assessed by pulse oximetry. Moreover, the patient's arterial waveform changed markedly from being supine to upright, suggesting that arterial flow patterns may be abnormal in our patient. Analysis of the waveform suggested a positional hypovolemia as the cause of his orthostatic intolerance. We review general aspects of arterial flow waveform analysis pertinent to health care providers and discuss the pathophysiology of POTS.

Comparison of physical examination and fluorodeoxyglucose positron emission tomography/computed tomography 4-6 months after radiotherapy to assess residual head-and-neck cancer.

PURPOSE: To retrospectively compare fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) and physical examination 4-6 months after radiotherapy for assessing residual head-and-neck cancer (HNC). METHODS AND MATERIALS: From July 2002 through March 2006, 52 HNC patients underwent definitive radiotherapy or chemoradiotherapy. Categoric assessments of residual tumor by PET/CT and physical examination 4-6 months after therapy were correlated and compared with clinical outcomes. Pretreatment data, including tumor stage and primary site standardized uptake value, were also gathered retrospectively and correlated with clinical outcomes. Median follow-up time was 58 months. RESULTS: Twenty-one patients had either locoregionally "positive" (17 of 21) or "equivocal" (4 of 21) PET/CT scans, whereas 31 patients had locoregionally negative scans. Four patients failed treatment and had biopsy-confirmed residual or recurrent local disease. All patients, including patients with locally suspicious scans or examinations who refused biopsies, were followed clinically for a minimum of 29 months after therapy, with no other cases of treatment failure detected during this time. No patient had residual nodal disease after therapy. Sensitivities of PET/CT vs. physical examination for early detection of treatment failure were 100% vs. 50%, whereas the specificities of the two modalities were 64.6% vs. 89.6%, respectively. Higher initial T stage and American Joint Commission on Cancer stage correlated with increased incidence of positive/equivocal PET/CT results and treatment failure. Maximal standardized uptake value was not predictive of any clinical outcome. CONCLUSIONS: A negative result on PET/CT obtained 4-6 months after radiotherapy is highly sensitive and correlates with successful locoregional control. Patients with negative scans may reasonably be spared invasive diagnostic procedures, such as biopsy and neck dissection, unless recurrent disease is suspected on clinical grounds. Close follow-up is prudent for HNC patients with abnormal findings on posttherapy PET/CT scan.

Sequence preference in RNA recognition by the nucleoporin Nup153.

The vertebrate nuclear pore protein Nup153 contains a novel RNA binding domain. This 150-amino acid region was previously found to bind preferentially to a panel of mRNAs when compared with structured RNAs, such as tRNA, U snRNA, and double-stranded RNA. The ability to broadly recognize mRNA led to the conclusion that the Nup153 RNA binding domain confers a general affinity for single-stranded RNA. Here, we have probed Nup153 RNA recognition to decipher how this unique RNA binding domain discriminates between potential targets. We first mapped the binding determinant within an RNA fragment that associates relatively robustly with the Nup153 RNA binding domain. We next designed synthetic RNA oligonucleotides to systematically delineate the features within this minimal RNA fragment that are key to Nup153 RNA-binding domain binding and demonstrated that the binding preferences of Nup153 do not reflect general preferences of an mRNA/single-stranded RNA-binding protein. We further found that the association between Nup153 and a cellular mRNA can be attributed to an interaction with specific subregions of the RNA. These results indicate that Nup153 can discriminate between mRNA and other classes of RNA transcripts due in part to direct recognition of a loose sequence motif. This information adds a new dimension to the interfaces that can contribute to recognition in mRNA export cargo selection and fate.

Metabolism of emulsions containing medium- and long-chain triglycerides or interesterified triglycerides.

This study compares the clearing and metabolism of three different lipid emulsions. They had the same phospholipid emulsifier and similar particle sizes. In one (LLL) the core component was long-chain triglycerides (TG), the second (MMM/LLL) contained equal molar amounts of medium- and long-chain TG, the third (MLM) contained synthetic TG with medium-chain (M) fatty acids in the 1,3-positions and a long-chain (L) fatty acid in the 2-position. In model experiments with bovine lipoprotein lipase, the MMM component was hydrolyzed preferentially in the MMM/LLL emulsion so that the initial products were M fatty acids and M monoglycerides. The MLM emulsion, in contrast, gave M fatty acids and formation of L-MG (monoglyceride) throughout hydrolysis. For in vivo studies [3H]oleic acid was incorporated into the emulsion TG as marker for the long-chain component. After bolus injection to rats, the MMM/LLL and MLM emulsions were cleared more rapidly than the LLL emulsion. This was true at all TG loads studied (4-64 mg for a 200 g rat). The labeled oleic acid was oxidized somewhat more rapidly when administered in the MLM emulsion compared to the MMM/LLL emulsion. There were only slight differences in tissue distribution of label. Hence, differences in in vivo metabolism of the long-chain fatty acids were small compared to the marked differences in TG structure and in patterns of product release during in vitro lipolysis.

Inhibition of lipases by phosphonates.

Ethyl hexylchlorophosphonate and analogues thereof were investigated as inhibitors of lipases. Both microbial and mammalian lipases were irreversibly inhibited. The inhibition could be monitored by p-nitrophenol release from the corresponding ethyl p-nitrophenyl hexylphosphonate inhibitor. Quantitative analysis of the data indicated that a 1:1 lipase-inhibitor complex was formed during inhibition. Enantioselective inhibition was found for the lipases derived from Candida antarctica and Rhizomucor miehei using pure enantiomers of ethyl p-nitrophenyl hexylphosphonate as inhibitors. Using the same inhibitor, reversed enantioselectivity was found for the protease alpha-chymotrypsin as compared to the two lipases.

Sterol effects on phospholipid biosynthesis in the yeast strain GL7.

Cells of the yeast sterol auxotroph GL7 were grown on either ergosterol or cholesterol to mid-logarithmic phase and total membrane fractions prepared. Activities of phospholipid biosynthetic enzymes in the two cell types were determined. The rates of phosphatidyl-ethanolamine-phosphatidyl-choline-N-methyl transferase and acyl-CoA-alpha-glycerol-3-phosphate transcylase were significantly greater in ergosterol-grown than in cholesterol-grown cells. These reactions were also inhibited by the polyene antibiotic filipin. By contrast the activities of long-chain fatty acyl-CoA synthetase, CTP-phosphatidate-cytidyl transferase, phosphatidylserine decarboxylase and of phosphatidylinositol synthetase were identical in the two (ergosterol and cholesterol) cultures and unaffected by filipin. The ergosterol effect on phosphatidyl-ethanolamine N-methyl transferase was greatest in cells harvested in early log phase, intermediate in the mid-log phase cells, and not significant in stationary phase cells.

6-Fluorocholesterol as a growth factor for the yeast mutant GL7.

6-Fluorocholesterol supports the growth of the sterol-requiring yeast mutant GL7 albeit less efficiently than cholesterol or ergosterol. When the fluoro analogue is combined with very much smaller amounts of cholesterol, the growth response to the sterol pair is synergistic, i.e., greater than additive. On further addition of trace amounts of ergosterol to the 6-fluorocholesterol-cholesterol pair, an additional synergistic growth response is observed. On 6-fluorocholesterol alone, the growth rate of the yeast mutant is slow initially, but after several transfers of such cells to the same media containing the fluoro analogue, growth improves substantially. When incorporated into artificial membranes, cholesterol and its 6-fluoro analogue have essentially identical effects on membrane fluidity as judged from microviscosity measurements. The contrasting responses of artificial membranes and whole cells to the 6-fluoro analogue of cholesterol might be due to sterol-protein interactions in natural membranes.

Prokaryotic triterpenoids. 1. 3 beta-Methylhopanoids from Acetobacter species and Methylococcus capsulatus.

3 beta-Methylbacteriohopanepolyol derivatives were isolated from three bacteria, Acetobacter pasteurianus ssp. pasteurianus, Methylococcus capsulatus and Nostoc muscorum, and identified by spectroscopic methods and direct comparison with 3 beta-methyldiplopterol and 3 beta-methylhopan-29-ol synthesized from 22-hydroxyhopan-3-one. The 3 beta-methylhopanoid content of A. pasteurianus ssp. pasteurianus could be dramatically increased (up to 60% of the total hopanoid content) by addition of L-methionine, the actual methyl donor, to the culture medium.

Prokaryotic triterpenoids. 2. 2 beta-Methylhopanoids from Methylobacterium organophilum and Nostoc muscorum, a new series of prokaryotic triterpenoids.

2 beta-Methylhopanoids, a new series of triterpenoids was identified from two prokaryotes. 2 beta-Methyldiplopterol was isolated from the methylotrophic bacterium Methylobacterium organophilum, and three different 2 beta-methylbacteriohopanepolyols from the cyanobacterium Nostoc muscorum. The structures of these compounds was deduced by direct comparison with 2 beta-methyldiplopterol synthesized from 22-hydroxyhopan-3-one.